• Molecules and Cells
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• v.40 no.7
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• pp.466-475
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• 2017

Dietary supplements have exhibited myriads of positive health effects on human health conditions and with the advent of new technological advances, including in the fields of proteomics, genomics, and metabolomics, biological and pharmacological activities of dietary supplements are being evaluated for their ameliorative effects in human ailments. Recent interests in understanding and discovering the molecular targets of phytochemical-gene-protein-metabolite dynamics resulted in discovery of a few protein signature candidates that could potentially be used to assess the effects of dietary supplements on human health. Persimmon (Diospyros kaki) is a folk medicine, commonly used as dietary supplement in China, Japan, and South Korea, owing to its different beneficial health effects including anti-diabetic implications. However, neither mechanism of action nor molecular biomarkers have been discovered that could either validate or be used to evaluate effects of persimmon on human health. In present study, Mass Spectrometry (MS)-based proteomic studies were accomplished to discover proteomic molecular signatures that could be used to understand therapeutic potentials of persimmon leaf extract (PLE) in diabetes amelioration. Saliva, serum, and urine samples were analyzed and we propose that salivary proteins can be used for evaluating treatment effectiveness and in improving patient compliance. The present discovery proteomics study demonstrates that salivary proteomic profile changes were found as a result of PLE treatment in prediabetic subjects that could specifically be used as potential protein signature candidates.

• Journal of Pharmacopuncture
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• v.9 no.2
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• pp.17-37
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• 2006

Objectives : To observe the changes in the serum proteins after intravenous injection of cultivated wild ginseng pharmacopuncture. Methods : Blood was collected before and after the administration of cultivated wild ginseng pharmacopuncture and only the serum was taken. Then differences in the spots on the scanned image after carrying out 2-Dimensional electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of cultivated wild ginseng pharmacopuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 1302, 2205, 3105, 7104, 8006, spots with more than one-time increase were 1101, 1505, 2013, 2403, 3009, 3010, 4002, 4009, 6704, 8101, and spots with decrease were 205, 801, 803, 3205, 5202, 6105, 6106, 7103, 9001, 9003. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1l01 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAPl protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein Ll, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as transferrin, 9001 as (Alpha-Oxy, Beta-(Cl12g)deoxy) T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d(204), which acts against microbes and pathogenic organisms, was increased by more than two-times after the administration of pharmacopuncture. 5. Antitrypsin(803), which is secreted with inflammatory response in the lungs, was reduced after the administration of pharmacopuncture. 6. Proapolipoprotein(2013, 3010) and apolipoprotein(7104), key components of the HDL-cholesterol which plays an important role in preventing arteriosclerosis, were increased after the administration of pharmacopuncture. 7. Vitamin D binding protein(DBP, 2403), protecting the lung at the time of inflammatory response, was increased after the administration of pharmacopuncture. 8. Transthyretin(TTR, 3205), which is the main protein causing familial amyloid polyneuropathy(FAP), was decreased after the administration of pharmacopuncture. 9. Ras-related protein Ral-A(4002) that controls phospholipid metabolism, cytoskeletal formation, and membrane traffic, was increased after the administration of pharmacopuncture. 10. Testis-specific protein Y(8006), which takes part in determination of the gender, was increased by more than two-times after the administration of pharmacopuncture. 11. Transferrin(8101), which balances the iron level in the body, was increased after the administration of pharmacopuncture. Conclusion : Above results support the notion that intravenous injection of cultivated wild ginseng pharmacopuncture induce changes in serum proteins and this research can be a pioneer work in finding biomarkers.

• The Korean Journal of Pesticide Science
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• v.7 no.3
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• pp.188-197
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• 2003

Endocrine disrupting chemicals (EDCs) can alter hormone regulation that control reproductive system in animals. The effects of endosulfan, molinate, and alachlor that suspected to have examined disruption EDCs effect on a fish species of interest, Xiphophorus helleri (swordtail fish), were studied using vitellogenin (Vtg) and aromatase as diagnostic biomarkers. Induction of Vtg proteins was detected by RT-PCR in male fish treated with alachlor, and mixture of endosulfan and molinate in dose response manner. Also, induction of aromatase was detected by RT-PCR in male fish treated with alachlor, endosulfan, and mixture of endosulfan and molinate in sinlilar manner. In this study, swordtail fish exposed to endosulfan or molinate individually did not show any adverse effects. However, Vtg and aromatase expressions and apoptosis were detected in swordtail. fish exposed to the mixture of endosulfan and molinate. These results suggested that low concentrations of mixture of molinate and endosulfan individually do not affect swordtail fish, but may influence genital system, and induce apoptosis.

• Journal of Preventive Medicine and Public Health
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• v.39 no.4
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• pp.353-358
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• 2006

Objectives: An increase in the serum gamma-glutamyltransferase (GGT) concentration has been regarded as a marker of alcohol drinking or liver disease. Some reports, however, have suggested that the serum GGT may be a sensitive and early biomarker for the development of prediabetes and diabetes. In this study we investigated whether serum GGT is a reliable predictor of the incident impaired fasting glucose (IFG), including diabetes. Methods: We performed a prospective study for two years (2002-2004). We analyzed the periodic health examination data from a total of 4,711 men. The examinations were done in the years 2002 and 2004. The analyzed data included a self-questionnaire, a physical examination and the laboratory results. Both IFG and diabetes were defined as a serum fasting glucose concentration of more than 100 mg/dL and 126 mg/dL, respectively. Results: A total of 738 cases (15.7%) of incident IFG and 13 cases (0.3%) of diabetes occurred. The mean serum GGT concentrations were quite different between the normal (38.0 IU) and incident IFG groups (50.3 IU), and the incident diabetes group (66.0 IU) (p<0.001). After multivariable adjustment, the relative risks for incident IFG or diabetes across the baseline GGT categories (<10th, 10th-20th, 30th-40th, 50th-60th, 70th-80th and >90th percentile) were 1.0, 1.172 (0.769-1.785), 1.107 (0.725-1.689), 1.444 (0.934-2.232), 2.061 (1.401-3.031) and 2.545 (1.784-3.631) (p-value for trend: <0.001). The risks significantly increased with increasing levels of GGT for 2 years; when comparing the increased groups (<10%, 10-20%, >20%) versus the decreased over 20% group of GGT, the risks for IFG or diabetes were 1.334 (1.002-1.776), 1.613 (1.183-2.199) and 1.399 (1.092-1.794). Conclusions: Our findings suggest that serum GGT concentrations within its normal range may be an early predictor of the development of IFG and diabetes. As serum GGT is a relatively inexpensive test and a reliable marker, it might have important implications in public health promotion.

• Journal of Life Science
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• v.23 no.2
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• pp.190-196
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• 2013

The sea squirt, Halocynthia roretzi, has experienced mass mortality due to softness syndrome. The identification of disease-induced genes can provide insights into the development of this syndrome. To identify the genes, we performed differentially expressed gene (DEG) analysis. The expression of the phosphoglycerate kinase (HrPGK) gene was significantly decreased in diseased sea squirts compared to normal ones. We confirmed the result of the DEG analysis through RT-PCR and real-time PCR. In addition, we detected single nucleotide polymorphisms at position -106 (A/T) and -254 (G/T) in the HrPGK gene promoter by genotyping analysis. At the -106 site of the HrPGK gene, the frequency of the AA allele in disease-resistant sea squirts was about two-fold higher than that of sensitive ones, and the frequency of the TT allele in the disease-resistant sea squirts was about six-fold lower. At the -254 site of the HrPGK gene, the frequency of the GT and the GG allele was approximately two-fold higher and two-fold lower, respectively, in the disease-resistant sea squirts compared to the disease-sensitive ones. Analysis of the relationship between the genotypic variation at the -106/-254 promoter and the expression of HrPGK mRNA showed that HrPGK mRNA expression was higher in the -106/-254 AA/GT genotype samples than in the -106/254 TT/GG genotype ones. These results show that sea squirts harboring the AA/GT genotype may have more resistance to mortality than the sea squirts with other genotypes.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.6 no.2
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• pp.272-280
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• 1996

This study was to evaluate the associations between urinary S-Phenyl-mercapturic acid(S-PMA) as a new indicator of biological monitoring for low level of exposure to benzene and independent variables such as the air concentration of benzene in the breathing zone of workers, the years of work, and smoking. In this study the subjects were the total of 145 drawn from 53 workers who were occupationally exposed to benzene and 92 workers who were not. The results were as follows: 1. In the workplace geometric mean concentration of benzene in the breathing zone of workers was 0.31 ppm(0.02 - 3.26 ppm) for the spraying workers and 0.25 ppm(0.02 - 3.95 ppm) for the printing workers. 2. The geometric mean of uninary S-PMA for non exposed group was $8.9{\mu}g/g$ creatinine($0.6-72.3{\mu}g/g$ creatinine), 80.3% (74 workers) of the total non-exposed workers indicated less than $20{\mu}g/g$ creatinine of uninary S-PMA. The difference of uninary S-PMA by sex, age, smoking was not significant. 3. The geometric mean of urinary S-PMA for workers who were exposed to benzene was $37.2{\mu}g/g$ creatinine, and was four times higher than that of workers who were not exposed. And 79.3% (42 workers) of the total exposed workers indicated more than $20{\mu}g/g$ creatinine of urinary S-PMA. 4. Regarding the level of benzene in the air, urinary S-PMA was the highest level of $147.9{\mu}g/g$ creatinine in the workers who were exposed to air concentration of 0.5 ppm of benzene and was higher as the level in the air was increased. 5. The correlation coefficient between log urinary S-PMA and log benzene concentration in the breathing zone was 0.80, and the following linear equation was found between urinary log S-PMA and log benzene concentration in the breathing zone : log S-PMA(${\mu}g/g$ creatinine) = 0.564 log benzene in air(ppm) + 0.192 (n=53, r=0.80, p=0.000) In conclusion, the concentration of S-PMA in urine proved to be good parameter for biological monitoring benzene exposure at the workplace even at low level of benzene in air.

• Journal of Food Hygiene and Safety
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• v.29 no.2
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• pp.85-91
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• 2014

Deoxynivalenol (DON) and related trichothecene mycotoxins are extensively distributed in the cereal-based food and feed stuffs worldwide. Recent climate changes and global grain trade increased chance of exposure to more DON and related toxic metabolites in poorly managed production systems. Monitoring the biological and environmental exposures to the toxins are crucial in protecting human and animals from toxicities of the hazardous contaminants in food or feeds. Exposure biomarkers including urine DON itself are prone to shift to less harmful metabolites by intestinal microbiota and liver metabolic enzymes. De-epoxyfication of DON by gut microbes such as Eubacterium strain BBSH 797 and Eubacterium sp. DSM 11798 leads to more fecal secretion of DOM-1. By contrast, most of plant-derived DON-glucoside is also easily catabolized to free DON by gut microbes, which produces more burden to body. Phase 2 hepatic metabolism also contributes to the glucuronidation of DON, which can be useful urine biomarkers. However, chemical modification could be very typical depending on the anthropologic or genetic background, luminal bacteria, and hepatic metabolic enzyme susceptibility to the toxins in the diet. After toxin exposure, effect biomarkers are also important in estimating the linkage and mechanisms of foodborne diseases in human and animal population. Most prominent adverse effects are demonstrated in the DON-induced immunological and behavioral disorders. For instance, acutely elevated interleukin-8 from insulted gut exposed to dietaty DON is a dominant clinical biomarker in human and animals. Moreover, subchronic exposure to the toxins is associated with high levels of serum IgA, a biological mediator of IgA nephritis. In particular, anorexia monitoring using mouse models are recently developed to monitor the biological activities of DON-induced feed refusal. It is also mechanistically linked to alteration of serotoin and peptide YY, which are promising biomarkers of neurological disorders by the toxins. As animal-alternative biomonitoring, huamn enterocyte-based assay has been developed and more realistic gut mimetic models would be useful in monitoring the effect biomarkers in resposne to toxic contaminants in the future investigations.

• Journal of Korean Neurosurgical Society
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• v.60 no.1
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• pp.21-29
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• 2017

Objective : The purpose of this study was to analyze outcomes and identify prognostic factors in patients with cerebral metastases from non-small cell lung cancer (NSCLC) treated with gamma knife radiosurgery (GKS) particularly, focusing on associations of biomarkers and systemic treatments. Methods : We retrospectively reviewed the medical records of 134 patients who underwent GKS for brain metastases due to NSCLC between January 2002 and December 2012. Representative biomarkers including epidermal growth factor receptor (EGFR) mutation, K-ras mutation, and anaplastic lymphoma kinase (ALK) mutation status were investigated. Results : The median overall survival after GKS was 22.0 months (95% confidence interval [CI], 8.8-35.1 months). During follow-up, 63 patients underwent salvage treatment after GKS. The median salvage treatment-free survival was 7.9 months (95% CI, 5.2-10.6 months). Multivariate analysis revealed that lower recursive partition analysis (RPA) class, small number of brain lesions, EGFR mutation (+), and ALK mutation (+) were independent positive prognostic factors associated with longer overall survival. Patients who received target agents 30 days after GKS experienced significant improvements in overall survival and salvage treatment-free survival than patients who never received target agents and patients who received target agents before GKS or within 30 days (median overall survival: 5.0 months vs. 18.2 months, and 48.0 months with p-value=0.026; median salvage treatment-free survival: 4.3 months vs. 6.1 months and 16.6 months with p-value=0.006, respectively). To assess the influence of target agents on the pattern of progression, cases that showed local recurrence and new lesion formation were analyzed according to target agents, but no significant effects were identified. Conclusion : The prognosis of patients with brain metastases of NSCLC after GKS significantly differed according to specific biomarkers (EGFR and ALK mutations). Our results show that target agents combined with GKS was related to significantly longer overall survival, and salvage treatment-free survival. However, target agents were not specifically associated with improved local control of the lesion treated by GKS either development of new lesions. Therefore, it seems that currently popular target agents do not affect brain lesions themselves, and can prolong survival by controlling systemic disease status.

• Allergy, Asthma & Respiratory Disease
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• v.5 no.6
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• pp.307-311
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• 2017

Induced sputum and sputum cell count analysis is a test for the diagnosis of various respiratory diseases. In particular, it has long been used as an important biomarker in the diagnosis or characterization of asthma or eosinophilic bronchitis. Despite a relatively long history of this test, there has been no consensus report for conducting and interpreting the analyses in Korea. Based on this awareness and necessity, the Korean Academy of Asthma, Allergy and Clinical Immunology launched the Standardization Committee to review the international guidelines and the literature and to develop a consensus report on the diagnostic procedure and interpretation of the sputum induction test.

• The Korean Journal of Malacology
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• v.25 no.3
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• pp.213-222
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• 2009

In order to investigate contamination of heavy metal in seawater and cultured oyster, samples were collected November 2003 to July 2004 from 12 sites (13 sites for seawater) along the coast of Tongyeong, Korea. The mean concentrations of metal in oyster tissues were as follows: 0.09 (0.01-0.3) ${\mu}g/l$ for Cd, 0.47 (0.01-1.4) ${\mu}g/l$ for Cr, 0.59 (0.2-2.3) ${\mu}g/l$ for Ni, 1.02 (0.1-4.2) ${\mu}g/l$ for Pb and 0.48 (0.01-3.9) ${\mu}g/l$ for Hg in the seawater, whereas 2.45 (0-5.47) mg/kgDW for Cd, 3.63 (0.10-12.91) mg/kgDW for Cr, 3.2 (0.01-15.73) mg/kgDW for Ni, 3.51 (0.01-6.47) mg/kgDW for Pb and 0.39 (0.004-0.74) mg/kgDW for Hg, respectively. Most metal concentration values were below the permissible range for the related regulations. Mean bioconcentration factors (BCF) for each metal were as follows: 38,964 (1,771-207, 171) for Cd, 9,583 (1,231-80, 162) for Cr, 191 (3-20, 980) for Ni, 1,416 (245-5, 207) for Pb and 180 (5-716) for Hg, respectively. The BCF values from this study corresponded to the transitional phase from the pristine to the contaminated waters. Notably, Cd showed the highest BCF, which suggest that the Pacific oyster could be utilized as a useful biomarker for Cd contamination in sea water. The multidimensional scaling analysis suggested that the metal contaminants are mainly originated from combustion of fossil fuel and accumulated to oyster through food web.