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        Hyaluronidase-inhibitory activities of glycosaminoglycans from Liparis tessellatus eggs

        Ticar, B.F.,Rohmah, Z.,Mussatto, S.I.,Lim, J.M.,Park, S.,Choi, B.D. Applied Science Publishers 2017 Carbohydrate polymers Vol.161 No.-

        Polysaccharide fractions isolated from L. tessellatus eggs were purified and eluted using the DEAE-sepharose fast flow column. These were collected, tested and pooled based on their sugars content: F1, F2, and F3 which contain 26.8, 23.3, and 20.2% sulfated glycans; 34.5, 38.2, and 45.0% uronic acids; and 23.5, 19.0, and 7.5% acetylhexosamines and hexosamines, respectively. Hyaluronidase inhibitory effects of the fractions are in the order F3>F2>F1>Ascorbic acid, with F3 having the highest inhibition among the fractions and that of the standard, ascorbic acid. The electrospray ionization tandem mass spectrometry (ESI-MS/MS) confirmed the presence of uronic acids on F3, which could be a <SUP>0,2</SUP>A<SUB>2</SUB> fragment plus loss of methyl group which is very common among non-methylated, sulfated disaccharides.

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        A peroxisome proliferator-activated receptor gamma agonist attenuates neurological deficits following spinal cord ischemia in rats

        Kim, H.,Hwang, J.,Park, S.,Nahm, S.F.,Min, S.,Lim, C.,Park, K.,Han, S. C.V. Mosby Co 2014 Journal of Vascular Surgery Vol.59 No.4

        Objective: Neuroprotective effects of the peroxisome proliferator-activated receptor gamma (PPARγ) agonist in cerebral ischemia have been reported, but the effect of a PPARγ agonist on spinal cord ischemia has not been investigated. The objective of this study was to investigate the effect of a PPARγ agonist on spinal cord ischemia. Pioglitazone, a PPARγ agonist, was administered in a rat model of spinal cord ischemia, and the extent of neurological damage and histological alterations were assessed. Methods: Forty-five rats were randomly enrolled into one of the three groups: (1) pioglitazone group (group PIO): rats were treated with pioglitazone 24 hours before ischemia; (2) control group (group C): rats were treated with the same volume of saline 24 hours before ischemia; and (3) sham group (group sham): rats were treated with the same volume of saline 24 hours before the sham surgery. Spinal cord ischemia was induced using a balloon-tipped catheter placed on the proximal descending aorta. Neurologic function was assessed using the motor deficit index (0 = normal, 6 = complete paralysis) during the 48 hours after reperfusion. Histological and biochemical evaluations were then performed. Results: Compared with group C, group PIO presented with lower motor deficit index 48 hours after reperfusion (5.0 [4.0-6.0] vs 3.0 [2.0-3.0]; group C vs group PIO, respectively; P < .001). Group PIO presented with a higher number of normal motor neurons (10.7 [8.1-11.9] vs 14.7 [14.0-15.3]; group C vs group PIO, respectively; P = .009) and a smaller area of infarcts (48.4% [46.3%-54.0%] vs 16.8% [11.5%-18.3%]; group C vs group PIO, respectively; P = .009) when compared with group C. The degree of inflammatory reactions, assessed by microglia activities, was significantly reduced in group PIO. Oxidative stress level, assessed using malonydialdehyde assay, was significantly reduced in group PIO relative to group C (192.21% [173.5%-206.4%] of sham vs 141.1% [131.7%-152.1%] of sham; group C vs group PIO, respectively; P = .007). The sham group exhibited no abnormality upon neurological or histological examination. Conclusions: PPARγ agonist pioglitazone pretreatment significantly reduces infarct volume and attenuates neurological deficits following spinal cord ischemia. The possible mechanism of neuroprotection by PPARγ agonist may involve modulation of inflammatory reaction and oxidative stress.

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      • SCIESCOPUSKCI등재

        Effects of Different Products and Levels of Selenium on Growth, Nutrient Digestibility and Selenium Retention of Growing-finishing Pigs

        Tian, J.Z.,Yun, M.S.,Kong, C.S.,Piao, L.G.,Long, H.F.,Kim, J.H.,Lee, J.H.,Lim, J.S.,Kim, C.H.,Kim, Y.Y.,Han, In K. Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.1

        This experiment was conducted to evaluate the effects of different selenium (Se) products (inorganic, organic A, organic B) added at two supplemental dietary Se levels (0.1 and 0.3 mg/kg) on growth performance, nutrient digestibility and Se retention in growing-finishing pigs. A $3{\times}2$ factorial arrangement of treatments was used in a RCB design, with a non-Se-fortified basal diet serving as the negative control. A total of 56 crossbred pigs (28 male and 28 female pigs) initially weighing an average $28.45{\pm}0.53kg$ BW were allotted to each treatment with four pigs per pen on the basis of sex and weight. Two pigs per pen were selected and bled from the anterior vena cava at 3- weekly intervals to analyze Se concentration. In the growing phase (0-6 weeks), increased ADFI was observed when pigs were fed organic Se compared to those fed the control diet or inorganic Se treatment (p<0.05). Pigs fed inorganic Se had a great ADFI than pigs fed organic Se (p<0.05) in the late finishing phase (7-12 weeks), although there were no differences in whole period ADFI between organic or inorganic Se products. During 12 weeks of the whole experimental period, serum Se concentration increased linearly when dietary Se level increased regardless of Se products (p<0.05). Both dietary Se source (p<0.05) and Se level (p<0.01) influenced the Se concentration of various pig tissues at end of this experiment and Se content was the highest in the kidney. For the determination of nutrient digestibility, a metabolic trial was conducted in 3 replicates in randomized complete block (RCB) design. A total of 21 barrows ($50.21{\pm}0.62kg$ of average BW) were used in the metabolic study. Selenium supplementation had no effect on nutrient digestibility except for crude protein. Crude protein digestibility increased with dietary supplementation of organic Se (A) compared with other forms of Se products or control diet (p<0.05). Consequently, this experiment indicated that dietary Se products and levels had no effect on growth performance of pigs. Se concentration in tissues and serum was increased in proportion to dietary Se level, especially when organic Se was provided. Although pigs were fed organic forms of Se, bioavailability of organic forms varied among products, consequently bioactivity of organic products to the animals should be evaluated before practical application in animal feed.

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        Genetic polymorphism in pvmdr1 and pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries

        Lu, F.,Lim, C.S.,Nam, D.H.,Kim, K.,Lin, K.,Kim, T.S.,Lee, H.W.,Chen, J.H.,Wang, Y.,Sattabongkot, J.,Han, E.T. Verlag für Recht und Gesellschaft ; Elsevier 2011 Acta Tropica Vol.117 No.2

        Treatment failure of chloroquine for Plasmodium vivax infection has increased in endemic countries. However, the molecular mechanisms for resistance and in vitro susceptibility of P. vivax to chloroquine remain elusive. We investigated the prevalence of mutations in the pvmdr1 and pvcrt-o genes, and the copy number of the pvmdr1 gene in isolates from the Republic of Korea (ROK), Thailand, the Union of Myanmar (Myanmar), and Papua New Guinea (PNG). We also measured in vitro susceptibility of Korean isolates to antimalarial drugs. The pvmdr1 analysis showed that mutations at amino acid position Y976F of pvmdr1 were found in isolates from Thailand (17.9%), Myanmar (13.3%), and PNG (100%), but none from the ROK, and mutation at position F1076L was present in isolates from the ROK (100%), Thailand (60.7%), and Myanmar (46.7%). One copy of the pvmdr1 gene was observed in most isolates and double copy numbers of the gene were observed in two Thai isolates. In the exons of the pvcrt-o gene that were sequenced, a K10 insertion was present in isolates from Thailand (56.0%) and Myanmar (46.2%), and the wild type was found in all Korean isolates. The results suggest that gene polymorphisms and copy number variation was observed in isolates of P. vivax from Southeast Asian countries. In Korean isolates polymorphism as limited to the F1076L variant, and no isolates with high level of resistance were found by in vitro susceptibility determinations. Moreover, our results provide a baseline for future prospective drug studies in malaria-endemic areas.

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      • SCISCIESCOPUS
      • Amelioration of neurodegenerative diseases by cell death-induced cytoplasmic delivery of humanin

        Park, T.Y.,Kim, S.H.,Shin, Y.C.,Lee, N.H.,Lee, R.K.C.,Shim, J.H.,Glimcher, L.H.,Mook-Jung, I.,Cheong, E.,Kim, W.K.,Honda, F.,Morio, T.,Lim, J.S.,Lee, S.K. Elsevier Science Publishers 2013 Journal of controlled release Vol.166 No.3

        Inhibition of the early intracellular event that triggers neurodegenerative cascades and reversal of neuronal cell death are essential for effective treatment of Alzheimer's disease (AD). In this study, a novel therapeutic for AD, a transducible humanin with an extended caspase-3 cleavage sequence (tHN-C3), was developed and showed multiple mechanisms of therapeutic action. These included targeted delivery of anti-apoptotic protein humanin through the blood-brain barrier (BBB) to neuronal cells, specific inhibition of caspase-3 activation to inhibit the early triggering of AD progression, and delivery of humanin into the cytoplasm of neuronal cells undergoing apoptosis where it exerts its anti-apoptotic functions effectively. The tHN-C3 prevented neuronal cell death induced by H<SUB>2</SUB>O<SUB>2</SUB>, or soluble Aβ<SUB>42</SUB>, via Bax binding. In animal models of AD induced by amyloid beta, in Tg2576 mice, and in the rat middle cerebral artery occlusion model of stroke, tHN-C3 effectively prevented neuronal cell death, inflammatory cell infiltration into the brain, and improved cognitive memory. The therapeutic effectiveness of tHN-C3 was comparable to that of Aricept, a clinically approved drug for AD treatment. Therefore, tHN-C3 may be a new remedy with multiple therapeutic functions targeting the early and late stages of neurodegeneration in AD and other brain injuries.

      • SCIESCOPUSKCI등재

        Effects of Dietary Energy Concentration and Lysine on the Digestible Energy Ratio for Apparent Amino Acid Digestibility in Finishing Barrows

        Cho, S.B.,Lee, H.J.,Chung, I.B.,Long, H.F.,Lim, J.S.,Kim, Y.Y.,Han, In K. Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.2

        This experiment was performed to investigate the effects of two energy levels and four lysine:digestible energy (DE) ratios on the apparent digestibility of nutrients in finishing pigs. The experiment was conducted using a $2{\times}4$ randomized complete block (RCB) design with three replicates. Twenty-four cross-bred finishing barrows ((Landrace${\times}$Yorkshire)${\times}$Duroc) with an average body weight of $64.2{\pm}0.69kg$ were assigned to one of eight treatments. Each barrow was placed in an individual metabolism crate and dietary treatment and water was provided ad libitum. Diets were designed to contain lysine:ME ratios of 1.5, 1.8, 2.1 and 2.4 g/Mcal at 3.35 and 3.6 Mcal/kg of diet in a $4{\times}2$ factorial arrangement. Dry matter (DM), ash, Ca and P digestibility were not affected by energy density or lysine:DE ratios. Crude fat digestibility increased as the energy density increased from 3.35 to 3.6 Mcal of DE/kg. Increasing the lysine:DE ratio also increased crude protein digestibility. There were no interactions between energy density and lysine:DE ratio in terms of nutrient digestibility. Nitrogen excretion via feces was not affected by energy density and lysine:DE ratio, while nitrogen excretion via urine was significantly affected by energy density and lysine:DE ratio. The apparent digestibility of all amino acids except for isoluecine, arginine and aspartic acid as well as average values of essential amino (EAA), non-essential amino acids (NEAA) and total amino acid digestibility (p>0.05) were not affected by energy density. The apparent digestibility of all amino acids except for leucine, proline, alanine and tyrosine, NEAA and total amino acid digestibility were significantly affected by lysine: DE ratio (p<0.05). Interactive effects of energy and lysine:DE ratio also significantly affected amino acid digestibility except for isoleucine, alanine, cystine, leucine, phenylalanine, glutamine and proline (p<0.05). In conclusion, these results suggest that maintaining the appropriate lysine:DE ratio becomes more important as the energy density of the diet increases. Consequently, increasing the lysine:DE ratio can result in increased crude protein digestibility and urinary nitrogen excretion, although apparent protein digestibility and nitrogen excretion were not affected by energy density Furthermore, increasing the lysine:DE ratio also increased the apparent digestibility of essential amino acids, except for leucine, regardless of energy density. The optimum lysine:DE ratio for maximum essential amino acid digestibility of the $64.2{\pm}0.69kg$ pig is approximately 2.4 g of lysine/Mcal of DE.

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        Validation of ALK/ROS1 Dual Break Apart FISH Probe probe in non-small-cell lung cancer

        Lim, S.M.,Chang, H.,Cha, Y.J.,Liang, S.,Tai, Y.C.,Li, G.,Pestova, E.,Policht, F.,Perez, T.,Soo, R.A.,Park, W.Y.,Kim, H.R.,Shim, H.S.,Cho, B.C. Elsevier Scientific Publishers 2017 Lung cancer Vol.111 No.-

        Background: ALK and ROS1 gene rearrangements are distinct molecular subsets of non-small-cell lung cancer (NSCLC), and they are strong predictive biomarkers of response to ALK/ROS1 inhibitors, such as crizotinib. Thus, it is clinically important to develop an effective screening strategy to detect patients who will benefit from such treatment. In this study, we aimed to validate analytical performance of Vysis ALK/ROS1 Dual Break Apart Probe Kit (RUO) in NSCLC. Methods: Study population composed of three patient cohorts with histologically confirmed lung adenocarcinoma (patients with ALK rearrangement, patients with ROS1 rearrangement and patients with wild-type ALK and ROS1). Specimens consisted of 12 ALK-positive, 8 ROS1-positive and 21 ALK/ROS1-wild type formalin-fixed paraffin-embedded samples obtained from surgical resection or excisional biopsy. ALK rearrangement was previously assessed by Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular, Abbot Park, IL, USA) and ROS1 rearrangement was previously assessed by ZytoLight<SUP>®</SUP> SPEC ROS1 Break Apart Probe (ZytoVision, GmbH). All specimens were re-evaluated by Vysis ALK/ROS1 Dual Break Apart Probe Kit. FISH images were scanned on BioView AllegroPlus system and interpreted via BioView SoloWeb remotely. Results: For a total of 41 patient samples, the concordance of the results by Vysis ALK/ROS1 Dual Break Apart Probe Kit was evaluated and compared to the known ALK and ROS1 rearrangement status of the specimen. Of the 12 ALK-positive cases, hybridization with Vysis ALK/ROS1 Dual Break Apart Probe Kit was successful in 10 cases (success rate 10/12, 83%) and of these 10 cases, all showed ALK rearrangement (100% concordance with the results of Vysis ALK Break Apart FISH Probe Kit). Two of the ALK+ cases were excluded due to weak ROS1 signals that could not be enumerated. Of the 8 ROS1-positive cases, 6 cases were successfully evaluated using Vysis ALK/ROS1 Dual Break Apart Probe Kit. The success rate was 75% (6/8), and of these 6 cases, all showed ROS1 rearrangement, giving a 100% concordance with ZytoLight<SUP>®</SUP> SPEC ROS1 Break Apart Probe. Two of the cases were excluded due to weak ROS1 gold signal or high background. In the cohort of 21 wild-type cases, the success rate using Vysis ALK/ROS1 Dual Break Apart FISH Probe Kit was 85% (18/21) and the concordance with ALK and ROS1 probe kit was 100% (18/18). Conclusion: Vysis ALK/ROS1 Dual Break Apart Probe Kit (RUO) can detect ALK and ROS1 rearrangement simultaneously in NSCLC.

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