• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.249-255
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• 2022

Alzheimer's disease (AD) represents a major public health concern and has been identified as a research priority. Clinical research evidence supports that the core cerebrospinal fluid (CSF) biomarkers for AD, including amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau), reflect key elements of AD pathophysiology. Nevertheless, advances in the clinical identification of new indicators will be critical not only for the discovery of sensitive, specific, and reliable biomarkers of preclinical AD pathology, but also for the development of tests that facilitate the early detection and differential diagnosis of dementia and disease progression monitoring. The early detection of AD in its presymptomatic stages would represent a great opportunity for earlier therapeutic intervention. The chance of successful treatment would be increased since interventions would be performed before extensive synaptic damage and neuronal loss would have occurred. In this study, the importance of developing an early diagnostic method using cognitive decline biomarkers that can discriminate between normal, mild cognitive impairment (MCI), and AD preclinical stages has been emphasized.

• Animal Bioscience
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• v.36 no.9
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• pp.1336-1349
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• 2023

Objective: The study was conducted to screen differentially expressed miRNAs in sows at early pregnancy by high-throughput sequencing and explore its mechanism of action on embryo implantation. Methods: The blood serum of pregnant and non-pregnant Landrace×Yorkshire sows were collected 14 days after artificial insemination, and exosomal miRNAs were purified for high throughput miRNA sequencing. The expression patterns of 10 differentially expressed (DE) miRNAs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The qRT-PCR quantified the abundance of serum exosomal miR-192 in pregnant and control sows, and the diagnostic power was assessed by receiver operating characteristic (ROC) analysis. The target genes of DE miRNAs were predicted with bioinformatics software, and the functional and pathway enrichment analysis was performed on gene ontology and the Kyoto encyclopedia of genes and genomes terms. Furthermore, a luciferase reporter system was used to identify the target relation between miR-192 and integrin alpha 4 (ITGA4), a gene influencing embryo implantation in pigs. Finally, the expression levels of miRNAs and the target gene ITGA4 were analyzed by qRT-PCR, and western blot, with the proliferation of BeWo cells detected by cell counting kit-8 (CCK-8). Results: A total of 221 known miRNAs were detected in the libraries of the pregnant and non-pregnant sows, of which 55 were up-regulated and 67 were down-regulated in the pregnant individuals compared with the non-pregnant controls. From these, the expression patterns of 10 DE miRNAs were validated. The qRT-PCR analysis further confirmed a significantly higher expression of miR-192 in the serum exosomes extracted from pregnant sows, when compared to controls. The ROC analysis revealed that miR-192 provided excellent diagnostic accuracy for pregnancy (area under the ROC curve [AUC]=0.843; p>0.001). The dual-luciferase reporter assay indicated that miR-192 directly targeted ITGA4. The protein expression of ITGA4 was reduced in cells that overexpressed miR-192. Overexpression of miR-192 resulted in the decreased proliferation of BeWo cells and regulated the expression of cell cycle-related genes. Conclusion: Serum exosomal miR-192 could serve as a potential biomarker for early pregnancy in pigs. miR-192 targeted ITGA4 gene directly, and miR-192 can regulate cellular proliferation.

• Korean Journal of Radiology
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• v.23 no.4
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• pp.446-454
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• 2022

Objective: To evaluate whether hyperoxia-induced ΔR₁ (hyperO₂ΔR₁) can accurately identify histological infarction in an acute cerebral stroke model. Materials and Methods: In 18 rats, MRI parameters, including hyperO₂ΔR₁, apparent diffusion coefficient (ADC), cerebral blood flow and volume, and ¹⁸F-fluorodeoxyglucose uptake on PET were measured 2.5, 4.5, and 6.5 hours after a 60-minutes occlusion of the right middle cerebral artery. Histological examination of the brain was performed immediately following the imaging studies. MRI and PET images were co-registered with digitized histological images. The ipsilateral hemisphere was divided into histological infarct (histological cell death), non-infarct ischemic (no cell death but ADC decrease), and nonischemic (no cell death or ADC decrease) areas for comparisons of imaging parameters. The levels of hyperO₂ΔR₁ and ADC were measured voxel-wise from the infarct core to the non-ischemic region. The correlation between areas of hyperO₂ΔR₁-derived infarction and histological cell death was evaluated. Results: HyperO₂ΔR₁ increased only in the infarct area (p ≤ 0.046) compared to the other areas. ADC decreased stepwise from non-ischemic to infarct areas (p = 0.002 at all time points). The other parameters did not show consistent differences among the three areas across the three time points. HyperO₂ΔR₁ sharply declined from the core to the border of the infarct areas, whereas there was no change within the non-infarct areas. A hyperO₂ΔR₁ value of 0.04 s^-1 was considered the criterion to identify histological infarction. ADC increased gradually from the infarct core to the periphery, without a pronounced difference at the border between the infarct and non-infarct areas. Areas of hyperO₂ΔR₁ higher than 0.04 s^-1 on MRI were strongly positively correlated with histological cell death (r = 0.862; p < 0.001). Conclusion: HyperO₂ΔR₁ may be used as an accurate and early (2.5 hours after onset) indicator of histological infarction in acute stroke.

• Journal of Trauma and Injury
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• v.37 no.1
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• pp.13-19
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• 2024

Purpose: Trauma is an important public health concern, and it is important to increase the survival rate of patients with trauma and enable them to return to society in a better condition. Initial treatment in the emergency department (ED) is closely associated with the prognosis of patients with trauma. However, studies regarding laboratory biomarker tests that can help predict the prognosis of trauma patients are limited. Presepsin is a novel biomarker of inflammation that can predict a poor prognosis in patients with sepsis. This study aimed to determine whether presepsin could be used as a prognostic indicator in patients with polytrauma. Methods: The study included patients with trauma who had visited a single regional ED from November 2021 to January 2023. Patients who had laboratory tests in the ED were included and analyzed retrospectively through chart review. Age, sex, injury mechanism, vital signs, surgery, the outcome of ED treatment (admission, discharge, transfer, or death), and trauma scores were analyzed. Results: Overall, 550 trauma patients were enrolled; 59.1% were men, and the median age was 64 years (interquartile range, 48.8-79.0 years). Patients in a hypotensive state (systolic blood pressure, <90 mmHg; n=39) had higher presepsin levels (1,061.5±2,522.7 pg/mL) than those in a nonhypotensive state (n=511, 545.7±688.4 pg/mL, P<0.001). Patients hospitalized after ED treatment had the highest presepsin levels (660.9 pg/mL), followed by those who died (652.0 pg/ mL), were transferred to other hospitals (514.9 pg/mL), and returned home (448.0 pg/mL, P=0.041). Conclusions: Serum presepsin levels were significantly higher in trauma patients in a hypotensive state than in those in a nonhypotensive state. Additionally, serum presepsin levels were the highest in hospitalized patients with trauma, followed by those who died, were transferred to other hospitals, and returned home.

• Journal of Nutrition and Health
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• v.52 no.2
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• pp.206-216
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• 2019

Purpose: Management of the metabolic risk factors in diabetes patients is essential for preventing or delaying diabetic complications. This study compared the levels of the metabolic risk factors in diabetes patients according to the income levels, and examined the secular trends in recent decades. Methods: The data from the Korea National Health and Nutrition Examination Survey 1998 ~ 2014 were used. The diabetes patients were divided into three groups based on their household income levels. General information was obtained through self-administered questionnaires, and the blood biomarkers and blood pressure data were obtained from a health examination. Multivariable linear regression models were used to compare the metabolic biomarker levels according to the household income levels, adjusting for potential confounding factors. Results: The fasting blood glucose, hemoglobin A1c, and blood lipid (total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride) levels were similar in the three groups. During the survey period of 16 years, the blood pressure showed a significant decreasing trend with time in all groups (p < 0.001). In contrast, the fasting blood glucose (p = 0.004), total cholesterol (p < 0.001), and LDL-cholesterol levels (p = 0.007) decreased significantly, and the HDL-cholesterol level (p < 0.001) increased significantly in the highest-income groups. In the lowest-income group, the fasting blood glucose (p = 0.02), total cholesterol (p < 0.001), and triglyceride (p = 0.003) levels showed a significant decreasing trend over time. On the other hand, the middle-income group showed no significant change in any of the metabolic risk factors except for blood pressure. Conclusion: The level of management of metabolic risk factors according to the income level of Korean diabetes patients was similar. On the other hand, the highest- and lowest-income groups showed positive trends of management of these factors during 16 years of observation, whereas the middle-income group did not show any improvement.

• The Korean Journal of Food And Nutrition
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• v.29 no.4
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• pp.547-556
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• 2016

The purpose of this study was to investigate the relationship between frequency of coffee consumption, metabolic biomarkers, and nutrition intake in adult participants in the combined 2007~2009 Korean National Health and Nutrition Examination Survey (KNHANES). Subjects (2,095 males and 3,297 females) were classified according to sex and frequency of coffee consumption (${\leq}1$ time/month, ${\geq}2$ times/month and ${\leq}6$ times/week, 1 time/day, 2 times/day, 3 times/day) using food frequency questionnaires. Nutrition intake was analyzed using 24 h recall data. The 3 times/day coffee consumption group had a significantly higher age, and frequency of smokers and drinkers compared to the ${\leq}1$ time/month coffee consumption group in both male and female participants. Males in the 3 times/day coffee consumption group had a significantly lower HDL-cholesterol level, but females had a higher waist circumference compared with the ${\leq}1$ time/month coffee consumption group. Males in the 3 times/day coffee consumption group had a significantly lower nutrient density of fiber, vitamin B2, vitamin C, calcium and phosphorus compared with the ${\leq}1$ time/month coffee intake group. Females in the 3 times/day coffee consumption group had a significantly higher nutrient density of fat and niacin, but lower nutrient density of carbohydrate, calcium, phosphorus, and iron compared with the ${\leq}1$ time/month coffee intake group. In males, the frequency of coffee consumption was not associated with the levels of metabolic biomarkers. In females, the frequency of coffee consumption was positively associated with diastolic blood pressure after adjustments for multiple confounding factors, including age, BMI, smoking status, alcohol consumption, physical activity and energy intake. Coffee consumption was associated with decreased diastolic blood pressure in females. These findings suggest the importance of an awareness of the association between coffee consumption and metabolic risk.

• Safety and Health at Work
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• v.3 no.1
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• pp.17-21
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• 2012

Objectives: Asbestos-related diseases (ARDs) have increased globally over the decades, causing an economic burden and increased health care costs. It is difficult to predict the risk of development of ARDs and of respiratory disability among workers with a history of asbestos exposure. Blood based biomarkers have been reported as promising tools for the early detection of malignant mesothelioma. This study investigated whether serum soluble mesothelin-related peptide (SMRP) would reflect severity of disablement in compensable ARDs. Methods: SMRP levels were measured in a cohort of 514 asbestos-exposed subjects. Severity of ARDs was assessed by a Medical Authority comprising four specially qualified respiratory physicians. Severity of ARDs and SMRP levels were compared. Results: Mean (standard deviation) serum SMRP level in the population with compensable ARDs (n = 150) was 0.95 (0.65) nmol/L, and was positively associated with disability assessment (p = 0.01). Mean SMRP level in healthy asbestos-exposed subjects was significantly lower than those with pleural plaques (p < 0.0001) and in subjects with ARDs who received compensation (p < 0.01). Conclusion: This study indicates that serum SMRP levels correlate with severity of compensable ARDs. Serum SMRP could potentially be applied to monitor progress of ARDs. Further prospective work is needed to confirm the relationship between SMRP and disability assessment in this population.

• Clinical and Experimental Pediatrics
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• v.59 no.7
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• pp.298-302
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• 2016

Purpose: Recent reports showed that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) could be a useful biomarker of intravenous immunoglobulin (IVIG) unresponsiveness and coronary artery lesion (CAL) development in Kawasaki disease (KD). The levels of these peptides are critically influenced by age; hence, the normal range and upper limits for infants and children are different. We performed an age-adjusted analysis of plasma NT-proBNP level to validate its clinical use in the diagnosis of KD. Methods: The data of 131 patients with KD were retrospectively analyzed. The patients were divided into 2 groups-group I (high NT-proBNP group) and group II (normal NT-proBNP group)-comprising patients with NT-proBNP concentrations higher and lower than the 95th percentile of the reference value, respectively. We compared the laboratory data, responsiveness to IVIG, and the risk of CAL in both groups. Results: Group I showed significantly higher white blood cell count, absolute neutrophil count, C-reactive protein level, aspartate aminotransferase level, and troponin-I level than group II (P<0.05). The risk of CAL was also significantly higher in group I (odds ratio, 5.78; P=0.012). IVIG unresponsiveness in group I was three times that in group II (odds ratio, 3.35; P= 0.005). Conclusion: Age-adjusted analysis of plasma NT-proBNP level could be helpful in predicting IVIG unresponsiveness and risk of CAL development in patients with KD.

• Journal of Nutrition and Health
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• v.35 no.2
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• pp.213-222
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• 2002

The alkaline comet assay has been used with increasing popularity to investigate the level of DNA damage in biomonitoring studies within the last decade in Western countries. The purpose of this study was to evaluate the usefulness of the alkaline comet assay as a biomarker of oxidative DNA damage for monitoring in the Korean population, and also to evaluate the effect of nutritional status and lifestyle factors on H2O2 induced oxidative DNA damage measured by the alkaline comet assay in human lymphocytes. The study population consisted of 61 healthy Korean male volunteers, aged 20-28. Epidemiological background data including dietary habits, smoking habits and anthropometrical measurements were collected through personal interviews. After blood collection, the comet assay in peripheral lymphocytes and plasma lipids analysis was carried out and the results analyzed. Tail moment (TM) and tail length (TL) of the comet assay were use\ulcorner to measure DNA damage in the lymphocytes of the subjects. Statistically significant (p < 0.05) positive correlations were observed between DNA damage (TM or TL) and smoking habits expressed as cigarettes smoked per day and pack years (r = 0.311 and 0.382 for TM, r = 0.294 and 0.350 for TL, respectively). There were also significant positive correlations between DNA damage parameter and waist-hip ratio. Higher plasma triglyceride levels were associated with increased damage to DNA. There were no correlations between the consumption frequencies of vegetables and DNA damage to the subjects. However, consumption frequencies of fruit and fruit juice intake were inversely associated with the TM and TL. The results indicate that die comet assay is a simple, rapid and sensitive method for detecting lymphocyte DNA damage induced by cigarette smoking. Consumption of fruit or fruit juices could potentiall modify the damaged DNA in the human peripheral lymphocytes of young Korean men.

• 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.