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Biotransformation of Diterpenoids From Aralia continentalis Roots by the Genus Fusarium (곰팡이 Fusarium 속을 이용한 독활 뿌리 추출물로부터 디테르페노이드의 생물전환)

  • Keumok Moon;Seola Lee;Eunhye Jo;Areum Lee;Jaeho Cha
    • Journal of Life Science
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    • v.34 no.4
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    • pp.215-226
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    • 2024
  • Aralia continentalis is widely distributed in Far East Asian countries such as Korea, China, and Japan. A. continentalis has traditionally been used as an herbal remedy for various conditions, including analgesia, headache, inflammation, lameness, lumbago, rheumatism, and dental diseases in Korea. Previously, epi-continentalic acid, continentalic acid, and kaurenoic acid as major active biological compounds belonging to the diterpenoid class were identified. To synthesize diterpenoid derivatives with enhanced bioavailability, Fusarium fujikuroi was employed to biotransform diterpenoids due to its known antibacterial activity. This yielded two derivatives of kaurenoic acid, namely 16α-hydroxyent-kauran-2-on-19-oic acid and 2β, 16α-dihydroxy-ent-kauran-19-oic acid, with their chemical structures elucidated via NMR analysis. These derivatives exhibited increased polarity compared to kaur- enoic acid, as evidenced by their retention time on preparative HPLC using the ODS-A column and structural modifications. Evaluation of their antidiabetic activity targeting PTP1B, a negative regulator of the insulin signaling pathway, revealed inhibitory activities of 30.8% and 27.6%, respectively, at a concentration of 4 ㎍/ml. Additionally, both derivatives demonstrated low cytotoxicity, with an IC50 value 18 times higher than kaurenoic acid. Therefore, the augmented water solubility and reduced toxicity of 16α-hydroxy-ent-kauran-2-on-19-oic acid and 2β, 16α-dihydroxy-ent-kauran-19-oic acid, resulting from biotransformation by F. fujikuroi, render them promising candidates for industrial applications.

Anti-inflammatory effect of naringenin-7-O-phosphate in LPS-induced RAW 264.7 cells (LPS로 유도된 RAW 264. 7 대식세포에서 Naringenin-7-O-phosphate의 항염증 활성)

  • Hyehyun Hong;Tae-Jin Park;Byeong Min Choi;Yu-Jung Yi;Seung-Young Kim
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.46-52
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    • 2023
  • The most abundant flavanone of grapefruits, naringenin (NN), is well known for its hepatoprotective, anti-lipid peroxidation and anti-carcinogenic effects. We generated three derivatives from NN using this technique in previous studies. Among them, it was confirmed that naringenin-7-O-phosphate (N7P), whose biological and physicochemical properties were not reported, showed a water solubility 45 times higher than that of NN. Therefore, in this study, the anti-inflammatory activity was evaluated in RAW 264.7 cells to investigate the potential physiological activity of N7P. As a result, N7P showed nitric oxide (NO) inhibitory activity at concentrations that did not show toxicity. In addition, prostaglandin E2 (PGE2) showed significant inhibitory activity from the lowest concentration of 12.5 μM and showed increased inhibitory activity compared to NN. In addition, as a result of western blot, N7P showed increased cyclooxygenase-2 (COX-2) inhibitory activity than NN, and effectively inhibited NO and PGE2 by significantly inhibiting their expression pathways. N7P also inhibited inflammatory cytokines, including tumor necrosis factor-α, interleukin-6. Based on these results, we propose that N7P can be used as a potent antiinflammatory agent.

Case Report on NTBC Treatment of Type 1 Tyrosinemia Diagnosed through Newborn Screening (신생아 선별검사를 통해 진단된 1형 타이로신혈증의 NTBC 치료 사례 보고)

  • Ji Eun Jeong;Hwa Young Kim;Jung Min Ko
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.23 no.2
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    • pp.39-44
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    • 2023
  • Hereditary tyrosinemia type 1 (HT-1) is a metabolic disorder caused by biallelic pathogenic variants in the fumarylacetoacetate hydrolase (FAH) gene, which impairs the function of the FAH enzyme, resulting in the accumulation of tyrosine's toxic metabolites in hepatocytes and renal tubular cells. As a consequence, individuals with HT-1 exhibit symptomatic manifestations. Rapid diagnosis and treatment of HT-1 can prevent short-term death and long-term complications. A 15-day-old boy presented to the outpatient department with elevated levels of tyrosine on his newborn screening tests conducted at the age of 3 and 10 days, respectively. Further blood tests revealed increased levels of alpha-fetoprotein and amino acids including tyrosine and threonine. Urine organic acid tests indicated a significant elevation in tyrosine metabolites, as well as the presence of succinylacetone (SA), which led to the diagnosis of HT-1. Two pathogenic and likely pathogenic variants of FAH compatible with HT-1 were also detected. He began a tyrosine-restricted diet at one month old and received nitisinone (NTBC) at two months old. With continued treatment, the patient's initially elevated AFP level, detection of SA in the urine, and mild hepatomegaly showed improvement. During four years and seven months of treatment, there were no exceptional complications apart from an increase in tyrosine levels and a delay in speech. We report a case of tyrosinemia type 1 detected through newborn screening, treated with dietary restriction and NTBC, with a good prognosis.

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Testing the Potential of Sewage Sludge Gasification Solid Residues as a Circulating Resource by Physical Separation (하수슬러지의 가스화 고형 잔재물의 순환자원으로서 물리적 선별에 의한 잠재성 검토)

  • Donghyun Kim;Sunghyun Bae;Seongmin Kim;Seongsoo Han;Yosep Han;Gi Woon Kwon
    • Resources Recycling
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    • v.33 no.3
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    • pp.48-56
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    • 2024
  • In this study, physical property evaluation and physical separation of the target product were performed to investigate the possibility of using sewage sludge gasification solid residue (GSRs) as a circulating resource. Firstly, the GSRs used in this study was supplied by Sudokwon Landfill Management Corporation, and generally the GSRs was in the form of porous pellets with a particle size of several millimetres. In addition, the partially black areas were confirmed to be unburned and ungasified carbon, and the average carbon content was 5%. In addition, the content of silica, alumina and phosphorus oxide was more than 70% of the total content. It was confirmed that the metallic components of the wet grinding product were separated into individual elements. As a physical separation of metallic and non-metallic components was required, it was finally found that flotation screening was suitable. Accordingly, cationic and anionic surfactants were selected to separate metallic components in which a relatively large amount of non-metallic components were concentrated, and the separation characteristics were confirmed. As a result, it is expected that the concentration of non-metallic components such as silica, alumina and phosphorus will be easier than the separation of metallic components. Therefore, since it is possible to physically treat the gasified sludge residue, it is judged to have potential as a circular resource according to the proposed recycling method for the separated product.

Studies on the effect of phthalimido methyl-O,O-dimethyl-phosphorodithioate (Imidan) and its possible metabolites on the growth of rice plant (Phthalimido methyl-O,O-dimethyl phosphorodithioate (Imidan)과 그의 대사물질(代謝物質)이 수도(水稻) 생육(生育)에 미치는 영향(影響)에 관(關)한 연구(硏究))

  • Lee, Sung-Hwan;Lee, Dong-Suk;Lee, Jae-Koo
    • Applied Biological Chemistry
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    • v.7
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    • pp.105-117
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    • 1966
  • This experiment was conducted to investigate the effet of phthalimido-methyl-O,O-dimethyl-phosphorodithioate (Imidan) known as an acaricide and its possible metabolic products on the growth of plant, when sprayed on the leaves of rice plant. The results are summarized as follows. 1) Possible metabolic products of Imidan, the following compounds were synthesized or recrystallized for the present experiment a) N-Hydroxymethyl phthalimidem b) Phthalimide c) Phthalamidic acid d) Phthalic acid e) Anthranilic acid f) p-Amino benzoic acid g) p-Hydroxy benzoic acid h) Benzoic acid 2) Among the above materials, a), c), d), e), and Imidan were dissolved in a buffer solution respectively to be 10 and 20 p.p.m. and tested with the wheat coleoptile straight growth method. According to the results, Imidan inhibited the growth of coleoptile in both 10 and 20 p.p.m., whereas the others showed much better growth than the control, especially phthalamidic acid in 10 p.p.m. It appears that Imidan itself inhibits the coleoptile growth, whereas the metabolites derived from Imidan through various metabolisms, including hydrolysis in plant tissues show growth-regulating activity. (refer: Table 1, Fig. 1) 3) 20, 100 and 200 p.p.m. solutions of Imidall emulsion in xylene f·ere prepared. The lengths of shoot and root of rice seeds germinated on the re-respective media were measured after 12 days. The data showed that root was much more elongated in Imidan 20 p.p.m., whereas shoot in Imidan 100 p.p.m., respectively, than in the xylene control. An interesting finding was that xylene used as solvent had a tendency to inhibit seriously the root growth of rice seed. (refer: Table 2,5). 4) The emulsions of concentrations in 10, 25, 50 and 100 p.p.m's of control, Imidan, N-hydroxy methyl phthalimide, anthranilic acid, and phthalmide, respectively, were sprayed twice on the rice plant on pot. After a certain period of time lengths of rice culms were measured, showing that plots treated with Imidan and N-hydroxy methyl phthalimide exhibited much more growth than those of control and the others. 5) Loaves and stems of rice plant were sampled and extracted with dried acetone at the intervals of 3-, 5-, 7-, and 14 days after treated with Imidan 250 p.p.m. emulsion. This sample extracted with acetone was purified by means of prechromatographic purification method with acetonitrile and paperchromatographed to detect the following metabolic products. Imidan (Rf: 0.97-0,98), N-hydroxy-methyl phthalimide (Rf: 0.87) phthalimide (Rf: 0.86-0.87), phthalamidic acid (Rf: 0.13-0.14), phthalic acid (Rf: 0.02-0.03), benzoic acid (Rf: 0.42-0.43), p-amino benzoic acid or p-hydroxy benzoic acid (Rf: 0.08-0.09), and unidentified compounds (Rf: 0.73, 0.59, 0.33, 0.23. 0.07). In addition, in the early stages, such as 3- and 5 days nonhydrolyzed Imidan and its first hydrolytic product, N-hydroxymethyl phthalimide were detected in relatively large amounts, whereas in the last stages of 7- and 14 days due to further decomposition, the afore-mentioned two materials were reduced in the amount and p-hthalic, phthalamidic, benzoic, and p-Hydroxy benzoic, or p-Amino benzoic acids were detected in a considerably large amount. It is, therefore, believed that most of Imidan applied to the leaves of rice plant may be decomposed within almost 14 days. In the light of above observations it is considered that Imidan itself is not involved in plant growth regulating activity, whereas various phthaloyl derivatives produced in the course of metabolism (namelr, enzymic action) in plant tissues may have such effect.

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Fermentation and Microbial Characteristics of Korean Traditional Fermented Milk, Tarak (시판 막걸리로 제조한 전통발효유 타락의 발효 특성)

  • Jung, Jin-Kyoung;Ko, Seong-Hee;Oh, Se-Wook;Lim, Ji-Young;Chun, Tae-Hoon;Kim, SooA;Myoung, Kil-Sun;Jang, Sung Seek;Huh, Chul-Sung;Han, Young-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.4
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    • pp.602-609
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    • 2015
  • In this study, for modernization of Korean traditional fermented milk, Tarak was made using four kinds of commercial Makgeolli based on the ancient cookbook Suwoonjabbang. Samples of Tarak were periodically collected during 24 h of fermentation at $37^{\circ}C$. After fermentation, changes in pH, titration acidity, and viscosity were analyzed. Fermentation metabolites, including organic acids and free sugars, were analyzed by HPLC. Numbers of yeast and lactic acid bacteria during 24 h of fermentation were measured. The pH of Tarak significantly decreased (P<0.01), whereas its acidity significantly increased (P<0.01) during fermentation. The viscosity increased during 8~24 h of fermentation until curd was separated in Tarak. The level of ethanol increased from 0.37~0.52 mg/mL to 0.51~0.71 mg/mL during 24 h of fermentation. Lactic acid and lactose were the major organic acid and free sugar in Tarak, respectively. The number of lactic acid bacteria increased from 5.23~6.25 log CFU/mL to 9.87~10.41 log CFU/mL at the beginning during 24 h of fermentation. The number of yeast increased from 5.14~6.47 log CFU/mL to 6.99~7.73 at the beginning during 24 h of fermentation at $37^{\circ}C$. The major strains of Tarak were Pediococcus acidilactici, Lactobacillus fermentun, Lactobacillus curvatus, and Saccharomyces cerevisiae. Therefore, we concluded that Tarak was a fermented milk by both lactic acid bacteria and yeast, which was similar to koumiss or kefir.

A prognosis discovering lethal-related genes in plants for target identification and inhibitor design (식물 치사관련 유전자를 이용하는 신규 제초제 작용점 탐색 및 조절물질 개발동향)

  • Hwang, I.T.;Lee, D.H.;Choi, J.S.;Kim, T.J.;Kim, B.T.;Park, Y.S.;Cho, K.Y.
    • The Korean Journal of Pesticide Science
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    • v.5 no.3
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    • pp.1-11
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    • 2001
  • New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.

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Detection of Copy Number Variation of the KIT Gene in the Landrace Breed using an Quantitative Oligonucleotide Ligation Assay(qOLA) (Quantitative Oligonucleotide Ligation Assay(qOLA)를 이용한 Landrace 품종의 KIT 유전자 반복수 변이 탐지)

  • Seo, B.Y.;Kim, J.H.;Nahm, D.W.;Yoo, C.K.;Lee, S.H.;Lee, J.B.;Lim, H.T.;Jung, E.J.;Cho, I.C.;Heo, K.N.;Jeon, J.T.
    • Journal of Animal Science and Technology
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    • v.49 no.5
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    • pp.559-568
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    • 2007
  • Recently, copy number variations (CNV) of genes or genomic segments have been intensively studied and various analysis methods have been developed. In this study, quantitative oligonucleotide ligation assay (qOLA) was applied to investigate CNV of KIT gene in the Landrace breed. A combined assay using qOLA and pyrosequencing, 6 genotype classes, I1/I1 or I3/i (IBe), I1/I2 or I3/IP, I1/I3, I1/IP or I2/i (IBe), I2/I2and I2/IP, were identified from 44 Landrace pigs. Genotype assignment using grouping features of measurements on a scatter plot showed 100% agreement with those using a statistical assignment by PROC FASTCLUS procedure implemented in the SAS package. Two versions (3100 and 3130) of ABI sequencers gave the same genotyping results, indicating there was no influence on qOLA by different versions of instrument, however, the means of standard deviation and coefficient of variation from the qOLA on a ABI 3130 (2.33 and 4.10) was lower than those from the qOLA on a ABI 3100 (2.67 and 4.81). Effect of proteinase K treatment on the PCR product followed by qOLA was very clear because noise peaks were disappeared and the observed ration fit better to the reference ratio corresponding to each genotype.

Biostatic activity of Coix lacryma seed extract on Toxoplasma gondii in macrophages (율무씨 수침 추출물이 대식세포내 톡소포자충에 미치는 영향에 관한 실험적 연구)

  • 소진탁;김숙향
    • Parasites, Hosts and Diseases
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    • v.34 no.3
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    • pp.197-206
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    • 1996
  • Water extract of Coix locrvmn seeds (Co-Ex) was separated into several components; dissolved with Tris-Cl buffer and the supernatant (WC 1), ammonium sulfate treatment supernatant (WC2) and the pellet nvc31,9AE column chromatography of WC 1 and the peak portions; WC4, WCS and WC6. Murine peritoneal macrophages in DMEM containing 10% heat-inactivated FCS were infected with tachyzoites of ToxopIQsmc gondii, RH strain, in uifo. By adding modulators such as Co-Ex, WC 1,2,3,4.5,6 and LPS or IFN-γ for 24 hrs . toxoplasmastatic activity of macrophages was examined in relation to nitrite production. Nitrite production of macrophages was enhanced especially in the series of WC2, WC1 and the combination sample (WC1 + WC2 + WC3) by order than other components or fractions (WC4, WC5, WC6) tested . Toxoplasmastatic actions such as percentage of the inacrophages infected by T. gonnii and fold increase of T gondii in macrophages showed retroverse relations with the amount of nitrite production; i.e. as nitric oxide (NO) increased the phagocytic index of macrophages and the fold increase of tachyzoites in macrophages decreased . Nitrite (NO-2) production was increased by adding IFN-γ in all cases together with enhancement of biostatic effects. Through the results obtained, it is speculated that some components other than the non-proteinous and defatted components in Coix lacrwmn seeds may contribute to activate macrophages through induction of NO for the biostatic activity.

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The Evaluation of the Difference of the SUV Caused by DFOV Change in PET/CT (PET/CT 검사에서 확대된 표시시야가 표준섭취계수에 미치는 영향 평가)

  • Kwak, In-Suk;Lee, Hyuk;Choi, Sung-Wook;Seok, Jae-Dong
    • The Korean Journal of Nuclear Medicine Technology
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    • v.15 no.2
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    • pp.13-20
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    • 2011
  • Purpose: The limited FOV(Field of View) of CT (Computed Tomography) can cause truncation artifact at external DFOV (Display Field of View) in PET/CT image. In our study, we measured the difference of SUV and compared the influence affecting to the image reconstructed with the extended DFOV. Materials and Methods: NEMA 1994 PET Phantom was filled with $^{18}F$(FDG) of 5.3 kBq/mL and placed at the center of FOV. Phantom images were acquired through emission scan. Shift the phantom's location to the external edge of DFOV and images were acquired with same method. All of acquired data through each experiment were reconstructed with same method, DFOV was applied 50 cm and 70 cm respectively. Then ROI was set up on the emission image, performed the comparative analysis SUV. In the clinical test, patient group shown truncation artifact was selected. ROI was set up at the liver of patient's image and performed the comparative analysis SUV according to the change of DFOV. Results: The pixel size was increase from 3.91 mm to 5.47 mm according to the DFOV increment in the centered location phantom study. When extended DFOV was applied, $_{max}SUV$ of ROI was decreased from 1.49 to 1.35. In case of shifted the center of phantom location study, $_{max}SUV$ was decreased from 1.30 to 1.20. The $_{max}SUV$ was 1.51 at the truncated region in the extended DFOV. The difference of the $_{max}SUV$ was 25.9% higher at the outside of the truncated region than inside. When the extended DFOV was applied, $_{max}SUV$ was decreased from 3.38 to 3.13. Conclusion: When the extended DFOV was applied, $_{max}SUV$ decreasing phenomenon can cause pixel to pixel noise by increasing of pixel size. In this reason, $_{max}SUV$ was underestimated. Therefore, We should consider the underestimation of quantitative result in the whole image plane in case of patient study applied extended DFOV protocol. Consequently, the result of the quantitative analysis may show more higher than inside at the truncated region.

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