1.Institutional Review Board (IRB) Mutual Recognition Program and Its Feasibility in Korea.
Hye Rim CHEONG ; Hyeon Woo YIM ; Byungin CHOE ; Yeong In KIM
Journal of Korean Society for Clinical Pharmacology and Therapeutics 2011;19(2):152-165
BACKGROUND: The use of Cooperative Institutional Review Board (Co-IRB) has become subject to continuous discussion. As a result, leading mainly by the Korea Association of Institutional Review Boards (KAIRB), "IRB mutual recognition program (MR-IRB)" was proposed. However operational methods of the program are still controversial. The object of this research is to examine domestically feasible scope and operation methods of MR-IRB by conducting survey. METHODS: 71 survey data was collected from chairman or specialist of each IRB and 29 IRB members of one institution running Central IRB was included. RESULTS: 76.5 % of respondents selected phase 3 multi-national, multi-center clinical Sponsor Initiated Trial as a suitable subject of MR-IRB, but only 50 % supported Investigator initiated trials, and answered early-stage clinical trials such as phase 1 clinical trials or biological agent trials are unsuitable due to relatively insufficient knowledge on risk level. In order to operate MR-IRB, standardized review criteria and agreement of institutions in building mutual trust is essential. Also it was learned from the survey that the most desirable way to adopt MR-IRB is to be initiated by the representing organization such as KAIRB based on mutual trust from institutional agreement. CONCLUSION: MR-IRB was recognized as one of Co-IRB. A suitable subjects of MR-IRB were preferred the phase 3 multi-national, multi-center clinical sponsor initiated trials to all kinds of clinical trials. This study suggests that based on real operation experience from MR-IRB pilot study, further study should be conducted to analyze pros and cons of MR-IRB and identify domestically eligible model to facilitate MR-IRB.
Surveys and Questionnaires
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Ethics Committees, Research
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Humans
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Korea
;
Pilot Projects
;
Research Personnel
;
Running
;
Specialization
2.Inherited metabolic diseases in the urine organic acid analysis of complex febrile seizure patients.
Hee Jeong CHEONG ; Hye Rim KIM ; Seong Soo LEE ; Eun Joo BAE ; Won Il PARK ; Hong Jin LEE ; Hui Chul CHOI
Korean Journal of Pediatrics 2009;52(2):199-204
PURPOSE: Seizure associated with fever may indicate the presence of underlying inherited metabolic diseases. The present study was performed to investigate the presence of underlying metabolic diseases in patients with complex febrile seizures, using analyses of urine organic acids. METHODS: We retrospectively analyzed and compared the results of urine organic acid analysis with routine laboratory findings in 278 patients referred for complex febrile seizure. RESULTS: Of 278 patients, 132 had no abnormal laboratory findings, and 146 patients had at least one of the following abnormal laboratory findings: acidosis (n=58), hyperammonemia (n=55), hypoglycemia (n=21), ketosis (n=12). Twenty-six (19.7%) of the 132 patients with no abnormal findings and 104 (71.2%) of the 146 patients with statistically significant abnormalities showed abnormalities on the organic acid analysis (P<0.05). Mitochondrial respiratory chain disorders (n=23) were the most common diseases found in the normal routine laboratory group, followed by PDH deficiency (n=2 ) and ketolytic defect (n=1). In the abnormal routine laboratory group, mitochondrial respiratory chain disorder (n=29) was the most common disease, followed by ketolytic defects (n=27), PDH deficiency (n=9), glutaric aciduria type II (n=9), 3-methylglutaconic aciduria type III (n=6), biotinidase deficiency (n=5), propionic acidemia (n=4), methylmalonic acidemia (n=2), 3-hydroxyisobutyric aciduria (n=2), orotic aciduria (n=2), fatty acid oxidation disorders (n=2), 2-methylbranched chain acyl CoA dehydrogenase deficiency (n=2), 3-methylglutaconic aciduria type I (n=1), maple syrup urine disease (n=1), isovaleric acidemia (n=1), HMG-CoA lyase deficiency (n=1), L-2-hydroxyglutaric aciduria (n=1), and pyruvate carboxylase deficiency (n=1). CONCLUSION: These findings suggest that urine organic acid analysis should be performed in all patients with complex febrile seizure and other risk factors for early detection of inherited metabolic diseases.
Acetyl-CoA C-Acetyltransferase
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Acidosis
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Acyl-CoA Dehydrogenase
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Amino Acid Metabolism, Inborn Errors
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Biotinidase Deficiency
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Brain Diseases, Metabolic, Inborn
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Electron Transport
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Fever
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Humans
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Hydroxybutyrates
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Hyperammonemia
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Hypoglycemia
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Isovaleryl-CoA Dehydrogenase
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Ketosis
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Maple Syrup Urine Disease
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Metabolic Diseases
;
Multiple Acyl Coenzyme A Dehydrogenase Deficiency
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Propionic Acidemia
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Pyruvate Carboxylase Deficiency Disease
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Pyruvate Dehydrogenase Complex Deficiency Disease
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Retrospective Studies
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Risk Factors
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Seizures
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Seizures, Febrile
3.Rat Model of Hindlimb Ischemia Induced via Embolization with Polyvinyl Alcohol and N-Butyl Cyanoacrylate.
Cheong Il SHIN ; Hyo Cheol KIM ; Yong Sub SONG ; Hye Rim CHO ; Kyoung Bun LEE ; Whal LEE ; Hwan Jun JAE ; Jin Wook CHUNG
Korean Journal of Radiology 2013;14(6):923-930
OBJECTIVE: To investigate the feasibility of a rat model on hindlimb ischemia induced by embolization from the administration of polyvinyl alcohol (PVA) particles or N-butyl cyanoacrylate (NBCA). MATERIALS AND METHODS: Unilateral hindlimb ischemia was induced by embolization with NBCA (n = 4), PVA (n = 4) or surgical excision (n = 4) in a total of 12 Sprague-Dawley rats. On days 0, 7 and 14, the time-of-flight magnetic resonance angiography (TOF-MRA) and enhanced MRI were obtained as scheduled by using a 3T-MR scanner. The clinical ischemic index, volume change and degree of muscle necrosis observed on the enhanced MRI in the ischemic hindlimb were being compared among three groups using the analysis of variance. Vascular patency on TOF-MRA was evaluated and correlated with angiographic findings when using an inter-rater agreement test. RESULTS: There was a technical success rate of 100% for both the embolization and surgery groups. The clinical ischemic index did not significantly differ. On day 7, the ratios of the muscular infarctions were 0.436, 0.173 and 0 at thigh levels and 0.503, 0.337 and 0 at calf levels for the NBCA, PVA and surgery groups, respectively. In addition, the embolization group presented increased volume and then decreased volume on days 7 and 14, respectively. The surgery group presented a gradual volume decrease. Good correlation was shown between the TOF-MRA and angiographic findings (kappa value of 0.795). CONCLUSION: The examined hindlimb ischemia model using embolization with NBCA and PVA particles in rats is a feasible model for further research, and muscle necrosis was evident as compared with the surgical model.
Animals
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*Disease Models, Animal
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Embolization, Therapeutic/*adverse effects
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Enbucrilate/administration & dosage/*toxicity
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Feasibility Studies
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Hindlimb/*blood supply
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Injections, Intra-Arterial
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Ischemia/*chemically induced/diagnosis
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Magnetic Resonance Angiography/*methods
;
Male
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Polyvinyl Alcohol/administration & dosage/*toxicity
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Rats
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Rats, Sprague-Dawley
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Tissue Adhesives/administration & dosage/toxicity
4.Functional Interaction of HIF-1 and NF-kappaB Increasing the Transcriptional Activation of TNF-alpha Gene in Monocytes.
Min Jeong PARK ; Sun Min LEE ; Soon Jung OK ; Hye Rim KIM ; Hyung Hoi KIM ; Jae Hun CHEONG
Korean Journal of Blood Transfusion 2013;24(1):21-32
BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine fulfilling a broad variety of immunoregulatory functions. Monocytes and macrophages play a pivotal role in inflammation and immune regulation. NF-kappaB and HIF-1 are known to increase expression of the TNF-alpha gene in a separate way. METHODS: Human monocytic leukemia, U937 cells, were transfected using the standard electroporation method for intracellular expression of NF-kappaB and HIF-1. We performed analysis using the mammalian two-hybrid assay and co-immunoprecipitation assay for detection of protein interaction of both proteins. In addition, chromatin immunoprecipitation analysis was performed for examination of NF-kappaB and HIF-1 binding on the TNF-alpha gene promoter. RESULTS: Here we show that NF-kappaB and HIF-1 cooperatively induced an increase in expression of the TNF-alpha gene dependent on promoter activity by the direct protein interaction of these two transcription factors. Hypoxia signaling induced marked enhancement of the transactivation of TNF-alpha promoter by HIF-1 and NF-kappaB. A tandem NF-kappaB/HIF-1 binding site was identified within the TNF-alpha promoter, which acted as a strong enhancer element. Physical association of the Rel domain of NF-kappaB and the N-TD domain of HIF-1 was required. Hypoxia treatment also resulted in a significant increase in the protein interaction of NF-kappaB and HIF-1 in vivo. Both transcription factors were recruited on the chromatin TNF-alpha promoter dependent on hypoxia stimuli. CONCLUSION: The results of this study indicate that a variety of extracellular signals for activation of TNF-alpha gene expression might converge on the transcriptional regulation through the NF-kappaB/HIF-1 signaling pathway.
Anoxia
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Binding Sites
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Chromatin
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Chromatin Immunoprecipitation
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Electroporation
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Enhancer Elements, Genetic
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Gene Expression
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Humans
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Immunoprecipitation
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Inflammation
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Leukemia
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Macrophages
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Monocytes
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NF-kappa B
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Proteins
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Transcription Factors
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Transcriptional Activation
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Tumor Necrosis Factor-alpha
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Two-Hybrid System Techniques
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U937 Cells
5.Assessment of Antioxidant and Phenolic Compound Concentrations as well as Xanthine Oxidase and Tyrosinase Inhibitory Properties of Different Extracts of Pleurotus citrinopileatus Fruiting Bodies.
Nuhu ALAM ; Ki Nam YOON ; Kyung Rim LEE ; Hye Young KIM ; Pyung Gyun SHIN ; Jong Chun CHEONG ; Young Bok YOO ; Mi Ja SHIM ; Min Woong LEE ; Tae Soo LEE
Mycobiology 2011;39(1):12-19
Cellular damage caused by reactive oxygen species has been implicated in several diseases, thus establishing a significant role for antioxidants in maintaining human health. Acetone, methanol, and hot water extracts of Pleurotus citrinopileatus were evaluated for their antioxidant activities against beta-carotene-linoleic acid and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, reducing power, ferrous ion-chelating abilities, and xanthine oxidase inhibitory activities. In addition, the tyrosinase inhibitory effects and phenolic compound contents of the extracts were also analyzed. Methanol and acetone extracts of P. citrinopileatus showed stronger inhibition of beta-carotene-linoleic acid compared to the hot water extract. Methanol extract (8 mg/mL) showed a significantly high reducing power of 2.92 compared to the other extracts. The hot water extract was more effective than the acetone and methanole extracts for scavenging DPPH radicals. The strongest chelating effect (92.72%) was obtained with 1.0 mg/mL of acetone extract. High performance liquid chromatography analysis detected eight phenolic compounds, including gallic acid, protocatechuic acid, chlorogenic acid, ferulic acid, naringenin, hesperetin, formononetin, and biochanin-A, in an acetonitrile and hydrochloric acid (5 : 1) solvent extract. Xanthine oxidase and tyrosinase inhibitory activities of the acetone, methanol, and hot water extracts increased with increasing concentration. This study suggests that fruiting bodies of P. citrinopileatus can potentially be used as a readily accessible source of natural antioxidants.
Acetone
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Acetonitriles
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Antioxidants
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Biphenyl Compounds
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Chlorogenic Acid
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Chromatography, Liquid
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Coumaric Acids
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Flavanones
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Fruit
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Gallic Acid
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Hesperidin
;
Humans
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Hydrochloric Acid
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Hydroxybenzoates
;
Isoflavones
;
Methanol
;
Monophenol Monooxygenase
;
Phenol
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Picrates
;
Pleurotus
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Reactive Oxygen Species
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Water
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Xanthine
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Xanthine Oxidase
6.Appraisal of Antihyperlipidemic Activities of Lentinus lepideus in Hypercholesterolemic Rats.
Ki Nam YOON ; Jae Seong LEE ; Hye Young KIM ; Kyung Rim LEE ; Pyung Gyun SHIN ; Jong Chun CHEONG ; Young Bok YOO ; Nuhu ALAM ; Tai Moon HA ; Tae Soo LEE
Mycobiology 2011;39(4):283-289
The wild edible mushroom, Lentinus lepideus has recently been cultivated for commercial use in Korea. While the mushroom has been widely used for nutritional and medicinal purposes, the possible anti-hyperlipidemic action is unclear. The effects of dietary L. lepideus on plasma and feces biochemical and on the liver histological status were investigated in hypercholesterolemic rats. Six-wk-old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. Biochemical and histological examinations were performed. A diet containing 5% L. lepideus fruiting bodies reduced plasma total cholesterol, triglyceride, low-density lipoprotein, total lipid, phospholipids, and the ratio of low-density to high-density lipoprotein. Body weight was reduced. The diet did not adversely affect plasma biochemical and enzyme profiles. L. lepideus reduced significantly plasma beta- and pre-beta-lipoprotein, while alpha-lipoprotein content was increased. A histological study of hepatic cells by conventional hematoxylin-eosin and oil red O staining revealed normal findings for mushroom-fed hypercholesterolemic rats. The present study suggests that a diet supplemented with L. lepideus can provide health benefits by acting on the atherogenic lipid profile in hypercholesterolemic rats.
Agaricales
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Animals
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Azo Compounds
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Body Weight
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Cholesterol
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Diet
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Electrophoresis, Agar Gel
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Feces
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Female
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Fruit
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Hepatocytes
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Humans
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Insurance Benefits
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Korea
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Lentinula
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Lipoproteins
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Liver
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Phospholipids
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Plasma
;
Rats
7.RNA-Seq for Gene Expression Profiling of Human Necrotizing Enterocolitis: a Pilot Study.
Kyuwhan JUNG ; InSong KOH ; Jeong Hyun KIM ; Hyun Sub CHEONG ; Taejin PARK ; So Hyun NAM ; Soo Min JUNG ; Cherry Ann SIO ; Su Yeong KIM ; Euiseok JUNG ; Byoungkook LEE ; Hye Rim KIM ; Eun SHIN ; Sung Eun JUNG ; Chang Won CHOI ; Beyong Il KIM ; Eunyoung JUNG ; Hyoung Doo SHIN
Journal of Korean Medical Science 2017;32(5):817-824
Necrotizing enterocolitis (NEC) characterized by inflammatory intestinal necrosis is a major cause of mortality and morbidity in newborns. Deep RNA sequencing (RNA-Seq) has recently emerged as a powerful technology enabling better quantification of gene expression than microarrays with a lower background signal. A total of 10 transcriptomes from 5 pairs of NEC lesions and adjacent normal tissues obtained from preterm infants with NEC were analyzed. As a result, a total of 65 genes (57 down-regulated and 8 up-regulated) revealed significantly different expression levels in the NEC lesion compared to the adjacent normal region, based on a significance at fold change ≥ 1.5 and P ≤ 0.05. The most significant gene, DPF3 (P < 0.001), has recently been reported to have differential expressions in colon segments. Our gene ontology analysis between NEC lesion and adjacent normal tissues showed that down-regulated genes were included in nervous system development with the most significance (P = 9.3 × 10⁻⁷; P(corr) = 0.0003). In further pathway analysis using Pathway Express based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, genes involved in thyroid cancer and axon guidance were predicted to be associated with different expression (P(corr) = 0.008 and 0.020, respectively). Although further replications using a larger sample size and functional evaluations are needed, our results suggest that altered gene expression and the genes' involved functional pathways and categories may provide insight into NEC development and aid in future research.
Axons
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Colon
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Enterocolitis, Necrotizing*
;
Gene Expression Profiling*
;
Gene Expression*
;
Gene Ontology
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Genome
;
Humans*
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Infant, Newborn
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Infant, Premature
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Mortality
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Necrosis
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Nervous System
;
Pilot Projects*
;
Sample Size
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Sequence Analysis, RNA
;
Thyroid Neoplasms
;
Transcriptome
8.Anticancer and Immunopotentiating Activities of Crude Polysaccharides from Pleurotus nebrodensis on Mouse Sarcoma 180.
Youn Jeong CHA ; Nuhu ALAM ; Jae Seong LEE ; Kyung Rim LEE ; Mi Ja SHIM ; Min Woong LEE ; Hye Young KIM ; Pyung Gyun SHIN ; Jong Chun CHEONG ; Young Bok YOO ; Tae Soo LEE
Mycobiology 2012;40(4):236-243
Pleurotus nebrodensis is an edible and commercially available mushroom in Korea. This study was conducted in order to evaluate the anticancer and immunopotentiating activities of crude polysaccharides, extracted in methanol, neutral saline, and hot water (hereafter referred to as Fr. MeOH, Fr. NaCl, and Fr. HW, respectively) from the fruiting bodies of P. nebrodensis. beta-Glucan and protein contents in Fr. MeOH, Fr. NaCl, and Fr. HW extracts of P. nebrodensis ranged from 23.79~36.63 g/100 g and 4.45~6.12 g/100 g, respectively. Crude polysaccharides were not cytotoxic against sarcoma 180, HT-29, NIH3T3, and RAW 264.7 cell lines at a range of 10~2,000 microg/mL. Intraperitoneal injection with crude polysaccharides resulted in a life prolongation effect of 11.76~27.06% in mice previously inoculated with sarcoma 180. Treatment with Fr. NaCl resulted in an increase in the numbers of spleen cells by 1.49 fold at the concentration of 50 microg/mL, compared with control. Fr. HW improved the immuno-potentiating activity of B lymphocytes through an increase in alkaline phosphatase activity by 1.65 fold, compared with control at 200 microg/mL. Maximum production of nitric oxide (14.3 microM) was recorded in the Fr. NaCl fraction at 200 microg/mL. Production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) was significantly higher, compared to control, and IL-6 production was highest, in contrast to TNF-alpha, IL-1beta, and positive control, concanavalin at the tested concentration of the various fractions. Results of the current study suggest that polysaccharides extracted from P. nebrodensis have a strong anticancer effect and may be useful as an ingredient of biopharmaceutical products for treatment of cancer.
Agaricales
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Alkaline Phosphatase
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Animals
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B-Lymphocytes
;
Cell Line
;
Fruit
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Immunomodulation
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Injections, Intraperitoneal
;
Interleukin-1beta
;
Interleukin-6
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Korea
;
Life Support Care
;
Methanol
;
Mice
;
Nitric Oxide
;
Pleurotus
;
Polysaccharides
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Sarcoma
;
Sarcoma 180
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Spleen
;
Tumor Necrosis Factor-alpha
;
Water