• Title/Summary/Keyword: novel compound

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Oral malodor-reducing effects by oral feeding of Weissella cibaria CMU in Beagle dogs (Weissella cibaria CMU 경구투여가 비글의 구취 저하에 미치는 효과)

  • Do, Kyung-Hyo;Park, Ho-Eun;Kang, Mi-Sun;Kim, Jong-Tae;Yeu, Ji-Eun;Lee, Wan-Kyu
    • Korean Journal of Veterinary Research
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    • v.58 no.2
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    • pp.87-94
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    • 2018
  • This study assessed the effects of Weissella cibaria (W. cibaria) CMU on oral health in male and female beagles (n = 18) by measuring oral malodor and periodontal disease-related parameters (calculus, plaque, and gingivitis indices). Oral malodor and indicators of periodontal disease were assessed in five treatment groups: negative control (scaling and 0.24 mg of maltodextrin, n = 3), positive control (0.24 mg of maltodextrin, n = 3), and W. cibaria CMU groups (each n = 4) at low (CMU-L, $2{\times}10^7$ colony forming unit [CFU]), medium (CMU-M, $2{\times}10^8CFU$), and high (CMU-H, $2{\times}10^9CFU$) concentrations. After feeding with W. cibaria CMU for 6 weeks, total volatile sulfur compound concentrations in the CMU-L ($2.0{\pm}1.04ng/10mL$), CMU-M ($2.4{\pm}1.05ng/10mL$), and CMU-H ($2.6{\pm}1.33ng/10mL$) groups were significantly lower than in the positive control group ($3.2{\pm}1.65ng/10mL$). Also, CMU-L ($1.4{\pm}0.83ng/10mL$) and CMU-H ($1.9{\pm}1.14ng/10mL$) groups had methyl mercaptan levels lower than that in the positive control group ($2.4{\pm}1.21ng/10mL$) at week 2. The plaque index was significantly lower in the CMU-H group ($4.5{\pm}0.28$) than in the positive control group ($5.9{\pm}1.08$) at week 6. W. cibaria CMU could be useful as a novel oral hygiene probiotics for reducing volatile sulfur compounds production and inhibiting plaque growth in companion animals.

Anti-proliferation Effects of Isorhamnetin on Lung Cancer Cells in Vitro and in Vivo

  • Li, Qiong;Ren, Fu-Qiang;Yang, Chun-Lei;Zhou, Li-Ming;Liu, Yan-You;Xiao, Jing;Zhu, Ling;Wang, Zhen-Grong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.3035-3042
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    • 2015
  • Background: Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. Objectives: To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. Materials and Methods: A549 cells were treated with $10{\sim}320{\mu}g/ml$ Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL). Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. Results: Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at $20{\mu}g/ml$, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. Conclusions: Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.

Preliminary evaluation of new 68Ga-labeled cyclic RGD peptides by PET imaging

  • Shin, Un Chol;Jung, Ki-Hye;Lee, Ji Woong;Lee, Kyo Chul;Lee, Yong Jin;Park, Ji-Ae;Kim, Jung Young;Kang, Joo Hyun;An, Gwang Il;Ryu, Young Hoon;Choi, Jae Yong;Kim, Kyeong Min
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.2 no.2
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    • pp.118-122
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    • 2016
  • Integrin ${\alpha}_v{\beta}_3$ plays an important role in the tumor metastases and angiogenesis. Arginine-glycine-aspartate (RGD) peptide motif binds to the integrin ${\alpha}_v{\beta}_3$. General $^{68}Ga$-labeled cyclic RGD peptides was rapidly eliminated from the circulatory system by renal excretion because of its hydrophilic property. The purpose of this study was to develop a novel $^{68}Ga$-labeled cyclic RGD peptides, which could acquire enhanced PET tumor images with improved pharmacokinetics by adopting biphenyl group between chelator and RGD peptides. $^{68}Ga$-DOTA-2P-c(RGDyK) was demonstrated a 12% higher lipophilicity level than $^{68}Ga$-DOTA-c(RGDyK) as a reference compound. In the animal PET, $^{68}Ga$-DOTA-2P-c(RGDyK) represented relatively lower blood-clearance, and an increased signal to noise ratio compared to $^{68}Ga$-DOTA-c(RGDyK). From these perspective, $^{68}Ga$-DOTA-2P-c(RGDyK) could be a good candidate for in integrin ${\alpha}_v{\beta}_3$-expressed tumor imaging.

Catechin Content and Antioxidative Effect from Rosa davurica Pall (생열귀나무의 카테킨 함량 및 항산화효과)

  • Shin, In-Cheol;Jeong, Kyung-Jin;Shim, Tae-Heum;Oh, Heung-Seok;Park, Sang-Kyun;Cheung, Eui-Ho;Kim, Suk-Nam;Kim, Gwang-Gee;Choi, Dae-Sung;Kwon, Yong-Soo;Kim, Chang-Min;Sa, Jae-Hoon
    • Korean Journal of Pharmacognosy
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    • v.33 no.3 s.130
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    • pp.177-181
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    • 2002
  • This study was carried out to investigate the antioxidative activities of Rosa davurica Pall for the purpose of development of novel antioxidant from natural products. Antioxidant activities of four different parts of Rosa davurica Pall such as fruit, leaf, stem and root were examined by measuring the radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. The methanol extract from the root of Rosa davurica Pall showed the highest antioxidative activity among 16 samples tested. And, we also tested radical scavenging effects of 5 different extract compartments(Hexane, $CHCl_3$, EtOAc, BuOH and $H_2O$ fraction). EtOAc and BuOH fractions from the root of Rosa davurica Pall exhibited antioxidative activities higher to those of natural, ${\alpha}-tocopherol$ or synthetic antioxidants, BHT. The antioxidative substance of EtOAc fraction from the root of Rosa davurica Pall was successively purified with silica gel adsorption column chromatography and Sephadex LH-20 column chromatography. The purified active substance was isolated as crystal and identified as (+)-catechin by $^{l}H-NMR$ and $^{13}C-NMR$. This compound exhibited DPPH radical scavenging activity with the $IC_50$ value of $1.7\;{\mu}g/ml$. In the analysis of catechin content, the leaf extracts contained the highest catechin, and fruit extracts contained the lowest catechin. Considering antioxidative activity on DPPH assay, the extracts of Rosa davurica Pall showed a possibility to be used as a new material for natural antioxidant and functional food.

Metabolic Engineering of the Brassinosteroid Biosynthetic Pathways (Brassinosteroid의 대사공학)

  • Lee, Mi-Ock;Song, Ki-Hong;Lee, Hyun-Kyung;Jung, Ji-Yoon;Choe, Vit-Nary;Choe, Sung-Hwa
    • Proceedings of the Korean Society of Plant Biotechnology Conference
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    • 2002.04b
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    • pp.69-75
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    • 2002
  • Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were Shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

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Recent research trends of post-harvest technology for king oyster mushroom (Pleurotus eryngii) (큰느타리버섯 수확후 관리기술 최근 연구 동향)

  • Choi, Ji-Weon;Yoon, YoeJin;Lee, Ji-Hyun;Kim, Chang-Kug;Hong, Yoon-Pyo;Shin, Il Sheob
    • Journal of Mushroom
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    • v.16 no.3
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    • pp.131-139
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    • 2018
  • The king oyster mushroom (Pleurotus eryngii) is widely consumed because of its flavor, texture, and its functional properties such as antioxidant activity and prebiotic effects. However, long-term product storage and transportation (e.g., export) are difficult because of its limited durability. The shelf-life of king oyster mushroom is affected by environmental factors such as temperature, humidity, gas composition, and ventilation, which may affect sensory characteristics including respiration rate, texture, moisture, flavor, color, and pH. The major problems regarding storage of mushrooms are browning, flavor changes, and softening. To address these problems, novel preservation techniques were developed, and more durable variants were bred. Different drying methods, gamma irradiation, chitosan coating, modified atmosphere (MA) packaging, and controlled atmosphere (CA) storage were evaluated in order to extend the shelf-life of king oyster mushrooms. Freeze drying showed better results for the preservation of mushrooms than other drying methods. Irradiation with 1 kGy was more effective for extending mushroom shelf-life than higher doses. The preservative performance of chitosan-based films was improved by combining the compound with other hydrocolloids, such as oil, protocatechuic acid, and wax. The CA storage conditions recommended for king oyster mushrooms are 5kPa $O_2$ and 10 to 15kPa $CO_2$ at temperatures below $10^{\circ}C$. Active MA packaging with microperforated PP film was also effective for maintaining quality during storage.

Metabolic Engineering of the Brassinosteroid Biosynthetic Pathways (Brassinosteroid의 대사공학)

  • Lee, Mi-Ock;Song, Ki-Hong;Lee, Hyun-Kyung;Jung, Ji-Yoon;Choe, Vit-Nary;Choe, Sung-Hwa
    • Journal of Plant Biotechnology
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    • v.29 no.2
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    • pp.139-144
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    • 2002
  • Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd /dwf3 were shown to be blocked in D$^4$reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bril/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRIl could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

AGL gene mutation and clinical features in Korean patients with glycogen storage disease type III (한국인 제3형 당원병 환자의 임상상 및 AGL 유전자형)

  • Ko, Jung Min;Lee, Jung Hyun;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.6 no.1
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    • pp.15-23
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    • 2006
  • Purpose: Glycogen storage disease type III (GSD-III), is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme is amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), which is responsible for the debranching of the glycogen molecule during catabolism. The disease has been demonstrated to show clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different patients. In this study, we analyzed mutations of the AGL gene in three unrelated Korean GSD-III patients and discussed their clinical and laboratory implications. Methods: We studied three GSD-III patients and the clinical features were characterized. Sequence analysis of 35exons and part exon-intron boundaries of the AGLgene in patients were carried out by direct DNA sequencing method using genomic DNA isolated from patients' peripheral leukocytes. Results: The clinical features included hepatomegaly (in all patients), seizures (in patient 2), growth failure (in patients 1), hyperlipidemia (in patients 1 and 3), raised transaminases and creatinine kinase concentrations (in all patients) and mild EKG abnormalities (in patients 2). Liver transplantation was performed in patient 2due to progressive hepatic fibrosis. Administration of raw-corn-starch could maintain normoglycemia and improve the condition. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 with c.1510_1511insT (p.Y504LfsX10), and patient 3 with c.3416 T>C (p.L1139P) and c.l735+1 G>T (Y538_R578delfsX4) mutations. Except R428K mutation, 4 other mutations identified in3 patients were novel. Conclusion: GSD-III patients have variable phenotypic characteristics resembling GSD-Ia. The molecular defects in the AGL gene of Korean GSD-III patients were genetically heterogeneous.

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A Case of Childhood-Onset Niemann Pick Type C Disease (소아기에 발현한 C형 Niemann Pick 병 1례)

  • Jung, Jiwon;Seo, Go Hun;Oh, Arum;Jin, Hee Kyung;Bae, Jae-Sung;Kim, Gu-Hwan;Yoo, Han-Wook;Lee, Beom Hee
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.18 no.1
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    • pp.30-34
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    • 2018
  • Niemann Pick type C disease (NPC) is an inherited progressive neurodegenerative disorder, due to defects of intracellular lipid trafficking and storage. Hepatosplenomegaly may prevail, while progressive neurodegenerative symptoms such as cerebellar involvement, dystonia, vertical supranuclear ophthalmoplegia, cataplexy, and eventually seizures starting at juvenile or late infantile period may accompany after normal early development. Here we describe a 3-year-old Korean boy with NPC who presented with splenomegaly at age 3. Liver biopsy showed characteristic foamy cell stained by periodic acid-schiff, and molecular analysis for NPC1 identified the compound heterozygous mutations, novel mutation of c.1631G>A (p.Trp544Ter) and c.2662C>T (p. Pro888Ser) as a known mutation. Filipin was strongly stained with unesterified cellular cholesterol in the patient's skin fibroblasts. The patient has received migulstat since age 3 years and his long-term outcome is needed to be observed.

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Clinical Features, Response to Treatment, Prognosis, and Molecular Characterization in Korean Patients with Inherited Urea Cycle Defects

  • Yoo, Han-Wook;Kim, Gu-Hwan;Seo, Eul-Ju
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.2 no.1
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    • pp.77-79
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    • 2002
  • The urea cycle, consisting of a series of six enzymatic reactions, plays key roles to prevent the accumulation of toxic nitrogenous compound and synthesize arginine de novo. Five well characterized diseases have been described, resulting from an enzymatic defect in the biosynthesis of one of the normally expressed enzyme. This presentation will focus on two representative diseases; ornithine transcarbamylase(OTC) deficiency and citrullinemia(argininosuccinate synthetase deficiency). OTC deficiency is one of the most common inborn error of urea cycle, which is inherited in X-linked manner. We identified 17 different mutations in 20 unrelated Korean patients with OTC deficiency; L9X, R26P, R26X, T44I, R92X, G100R, R141Q, G195R, M205T, H214Y, D249G, R277W, F281S, 853 del C, R320X, V323M and 10 bp del at nt. 796-805. These mutations occur at well conserved nucleotide sequences across species or CpG hot spot. The L9X and R26X lead to the disruption of leader sequences, required for directing mitochondrial localization of the OTC precursor. Their phenotypes are severe, and neonatal onset. The G100R, R277W and V323M mutations were uniquely identified in patients with late onset OTC deficiency. The other genotypes are associated with neonatal onset. Out of 20 patients with OTC deficiency, only 6 patients are alive; two were liver transplanted, and normal in growth and development at 2, 4 years after transplantation respectively. Citrullinemia is an autosomal recessive disease, caused by the mutations in the argininosuccinate synthetase(ASS) gene. We identified in 3 major mutations in 11 unrelated Korean patients with citrullinemia; G324S, $IVS6^{-2}$ A to G, and 67 bp ins at nt 1125-1126. Among these, the 67 base pair insertion mutation is novel. The allele frequency of each mutation is; G324S(45%), IVS6-2 A to G(32%), and 67 base pair insertion(14%). All patients are diagnosed at neonatal or infantile age. Interestingly, two patients presented with stroke like episode. Out of 11 patients, 5 patients died. Among 6 patients alive, one patient was successfully liver transplanted.

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