• Mass Spectrometry Letters
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• v.8 no.4
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• pp.114-118
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• 2017

While saliva can be considered as good biological fluid for monitoring biomarkers due to many advantages including its communication with blood and the non-invasive nature during its sampling, its applications to that purpose is still limited. As a part of efforts to expand the applications of saliva to the protein biomarker research, we carried out global absolute quantitation of proteins in human whole saliva (WS) by bottom-up proteomics techniques mainly based on nLC-Q-IMS-TOF employing $MS^E$. From the analyses of a pooled WS sample collected from 22 healthy Korean volunteers, 93 proteins ranging from $5.89{\times}10^1ng/mL$ (immunoglobulin heavy chain) to $1.59{\times}10^4ng/mL$ (${\alpha}-amylase$ 1) were confirmed. For the validation of the present results, human serum albumin in the same sample was quantitated by ELISA and its result was compared with that from the nLC-Q-IMS-TOF study. As a result, there was no significant difference between two results from individual approaches ($1.18{\times}10^4{\pm}0.03{\times}10^4 ng/mL$ from nLC-Q-IMS-TOF experiments vs. $1.23{\times}10^4{\pm}0.07{\times}10^4ng/mL$ from ELISA experiments, n=3, p=0.309). To our knowledge, this is the first global absolute quantitation of proteins in human whole saliva and information from the present study can be widely used as the first level reference for the discovery of new protein biomarkers from human whole saliva as well as for quantitative applications of human whole saliva proteins.

• Journal of Environmental Health Sciences
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• v.37 no.5
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• pp.358-368
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• 2011

Objectives: In order to evaluate the association between occupational exposure to chloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL), we conducted a meta-analysis of retrospective cohort studies and casecontrol studies and attempted to summarize the evidence of the association from molecular-epidemiological studies and experiments with human cells. Methods: In the meta-analysis, we restricted the analysis to those studies with data for chlorinated solvents, degreasers, or TCE. Studies involving dry cleaners or launderers were excluded from the analysis because use of TCE as a dry cleaning fluid has been rare since the 1960s. The data were combined using a random-effects model to estimate the summary risks (OR and RR) and 95% confidence intervals (CIs). Molecular evidence of the effect of TCE on human immune system were also reviewed and summarized. Results: Occupational exposure to TCE was strongly associated with NHL among cohort studies (number of studies=13, summary RR=1.33, 95% CI=1.04-1.70) whereas the association was not statistically significant among case-control studies (number of studies=15, summary OR=1.10, 0.98-1.23). When exposure level was considered, it became statistically significant for the highest exposure level (number of studies=5, summary OR=1.70, 1.25-2.32). Molecular evidences showed that TCE exposure in human or cultured human cells may cause a significant decrease immune cell subsets and changes in hormone levels related to immune response. Conclusions: Our results from meta-analysis and additional molecular evidence suggest that occupational exposure to TCE may cause NHL. However, unmeasured potential confounding and unclear dose-response relationships warrant further study on the role of TCE exposure in NHL carcinogenesis.

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2413-2418
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• 2013

Forensic and legal medicine require reliable data to indicate excessive alcohol consumption. Ethanol is oxidatively metabolized to acetate by alcohol dehydrogenase and non-oxidatively metabolized to ethyl glucuronide (EtG), ethyl sulfate (EtS), phosphatidylethanol, or fatty acid ethyl esters (FAEE). Oxidative metabolism is too rapid to provide biomarkers for the detection of ethanol ingestion. However, the non-oxidative metabolite EtG is a useful biomarker because it is stable, non-volatile, water soluble, highly sensitive, and is detected in body fluid, hair, and tissues. EtG analysis methods such as mass spectroscopy, chromatography, or enzyme-linked immunosorbent assay techniques are currently in use. We suggest that nuclear magnetic resonance (NMR) spectroscopy could be used to monitor ethanol intake. As with current conventional methods, NMR spectroscopy doesn't require complicated pretreatments or sample separation. This method has the advantages of short acquisition time, simple sample preparation, reproducibility, and accuracy. In addition, all proton-containing compounds can be detected. In this study, we performed $^1H$ NMR analyses of urine to monitor the ethanol and EtG. Urinary samples were collected over time from 5 male volunteers. We confirmed that ethanol and EtG signals could be detected with NMR spectroscopy. Ethanol signals increased immediately upon alcohol intake, but decreased sharply over time. In contrast, EtG signal increased and reached a maximum about 9 h later, after which the EtG signal decreased gradually and remained detectable after 20-25 h. Based on these results, we suggest that $^1H$ NMR spectroscopy may be used to identify ethanol non-oxidative metabolites without the need for sample pretreatment.

• Investigative Magnetic Resonance Imaging
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• v.23 no.3
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• pp.241-250
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• 2019

Purpose: The purpose of this study was to determine the relation between quantitative magnetic resonance imaging biomarkers, and clinical performances in chronic phase of carbon monoxide intoxication. Materials and Methods: Eighteen magnetic resonance scans and cognitive evaluations were performed, on patients with carbon monoxide intoxication in chronic phase. Apparent diffusion coefficient (ADC) ratios of affected versus unaffected centrum semiovale, and corpus callosum were obtained. Signal intensity (SI) ratios between affected centrum semiovale, and normal pons in T2-FLAIR (fluid-attenuated inversion recovery) images were obtained. The Mini-Mental State Exam, and clinical outcome scores were assessed. Correlation coefficients were calculated, between MRI and clinical markers. Patients were further classified into poor-outcome and good-outcome groups based on clinical performance, and imaging parameters were compared. T2-SI ratio of centrum semiovale was compared, with that of 18 sex-matched and age-matched controls. Results: T2-SI ratio of centrum semiovale was significantly higher in the poor-outcome group, than that in the good-outcome group and was strongly inversely correlated, with results from the Mini-Mental State Exam. ADC ratios of centrum semiovale were significantly lower in the poor outcome group than in the good outcome group, and were moderately correlated with the Mini-Mental State Exam score. Conclusion: A higher T2-SI and a lower ratio of ADC values in the centrum semiovale, may indicate presence of more severe white matter injury and clinical impairment. T2-SI ratio and ADC values in the centrum semiovale, are useful quantitative imaging biomarkers for correlation with clinical performance in individuals with carbon monoxide intoxication.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.83-91
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• 2006

Background : For unknown reasons, the serum ferritin concentrations are higher in patients with acute lung injury. A pretreatment with aspirin reduces the acute lung injury in rats subjected severe hemorrhage, and increases the rate of ferritin synthesis in vitro. This study investigated the effect of aspirin on the serum ferritin changes in rats subjected to severe hemorrhage. Methods : Hemorrhagic shock was induced by withdrawing blood (20 ml/kg of B.W.) through the femoral artery for 5 min. The rats were pretreated with aspirin (10 mg/kg, i.v.) 30 min before hemorrhage. Results : The protein content and leukocyte count in the bronchoalveolar lavage fluid, lung tissue myeloperoxidase activities were significantly higher after hemorrhage. The aspirin pretreatment prevented these changes. The serum and lavage fluid ferritin concentrations were elevated higher after hemorrhage. These were also attenuated by the aspirin pretreatment. Conclusion : The changes in the serum and lung lavage ferritin level might be closely related to the severity of hemorrhage-induced acute lung injury. Therefore, the serum and lavage ferritin concentrations can be a useful biomarker for patients with precipitating conditions.

• The Korea Journal of Herbology
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• v.31 no.5
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• pp.71-78
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• 2016

Objectives : Diabetic nephropathy is one of the most common chronic complications of diabetes and a leading cause of end-stage renal failure in the world. Mesangial cell proliferation is known as the major pathologic features such as glomerulosclerosis and renal fibrosis. Wiryeongtang (WRT) is a well-known traditional herbal formula as therapeutic agents for chronic edema and dysuresia of renal homeostasis. In the present study, we investigated whether WRT inhibits high glucose (HG)-induced renal dysfunction by TGF-β/Smads signal regulation in cultured mesangial cells.Methods : Inhibitory effect of WRT (10-50 ㎍/ml) on HG-stimulated mesangial cells proliferation and dysfunction were evaluated by [³H]-thymidine incorporation, Western blot, and RT-qPCR.Results : WRT significantly decreased HG-accelerated thymidine incorporation in human renal mesangial cell in a dose-dependent levels. WRT induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21waf1/cip1 and p27kip1 expression. In addition, HG enhanced expression of dysfunction biomarker such as collagen IV and CTGF, which was markedly attenuated by WRT. WRT decreased TGF-β1 and Smad-2/Smad-4 expression, whereas increased Smad-7 expression under HG. Furthermore, WRT inhibited HG-induced inflammatory factors level such as ICAM-1 and MCP-1 as well as NF-κB p65 nuclear translocation and intracellular ROS production.Conclusions : These results suggested that WRT may alleviate mesangial proliferation and inflammation possibly involved in renal fibrotic process, further diabetic nephropathy through disturbing TGF-β1/Smad signaling and NF-κB/ROS pathway. Thus, WRT might prove to be effective in the treatment of renal dysfunction leading to diabetic nephropathy.