• Journal of Korean Neurosurgical Society
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• v.67 no.3
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• pp.333-344
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• 2024

Objective : Markers of neuroinflammation during ischemic stroke are well characterized, but additional markers of neural damage are lacking. The study identified associations of behavioral disorders after stroke with histologic neural damage and molecular biological change. Methods : Eight-week-old, 25 g male mice of the C57BL/6J strain were subjected to middle cerebral artery occlusion (MCAO) to induce ischemic stroke. The control group was a healthy wild type (WT), and the experimental group were designed as a low severity MCAO1 and a high severity MCAO2 based on post-stroke neurological scoring. All groups underwent behavioral tests, realtime polymerase chain reaction, triphenyltetrazolium chloride (TTC) staining and Hematoxylin and Eosin staining. One-way analysis of variance was used to analyze statistical significance between groups. Results : In TTC staining, MCAO1 showed 29.02% and MCAO2 showed 38.94% infarct volume (p<0.0001). The pro-inflammatory cytokine interleukin (IL)-1β was most highly expressed in MCAO2 (WT 0.44 vs. MCAO1 2.69 vs. MCAO2 5.02, p<0.0001). From the distance to target in the Barnes maze test, WT had a distance of 178 cm, MCAO1 had a distance of 276 cm, and MCAO2 had a distance of 1051 (p=0.0015). The latency to target was 13.3 seconds for WT, 27.9 seconds for MCAO1, and 87.9 seconds for MCAO2 (p=0.0007). Prospero homeobox 1 (Prox1) was most highly expressed in MCAO2 (p=0.0004). Doublecortin (Dcx) was most highly expressed in MCAO2 (p<0.0001). Conclusion : The study demonstrated that histological damage to neural cells and changes in brain mRNA expression were associated with behavioral impairment after ischemic stroke. Prox1 and Dcx may be biomarkers of neural damage associated with long-term cognitive decline, and increased expression at the mRNA level was consistent with neural damage and long-term cognitive dysfunction.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.467-476
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• 2023

Schisandra chinensis (S. chinensis) is a deciduous broad-leaved cave plant belonging to the Schisandraceae family and is widely distributed in East Asia including Korea, Japan, China, and Taiwan. It has been reported that the main components contained in S. chinensis include lignan compounds and triterpenoid compounds. To distinguish the characteristics of S. chinensis by production region of Korea, a discriminant was established by performing metabolite profiling and principal component analysis, a multivariate statistical analysis technique. As a result, 16 types of triterpenoids, 9 types of lignan, and 1 type each of flavonoid, phenylpropanoid, and fatty acid were identified. In addition, through multivariate statistical analysis, it was confirmed that the four groups in Danyang, Moongyeong, Geochang, and Pyeongchang were divided, by applying the s-plot model of orthogonal partial least squares discriminant analysis. Biomarkers were identified: lanostane, cycloartane, schiartane triterpenoid, and dibenzocyclo-octadiene lignan were identified as chemical markers, respectively.

• Journal of Microbiology and Biotechnology
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• v.34 no.3
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• pp.606-621
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• 2024

This study evaluated the hepatoprotective effect of fermented Protaetia brevitarsis larvae (FPB) in ethanol-induced liver injury mice. As a result of amino acids in FPB, 18 types of amino acids including essential amino acids were identified. In the results of in vitro tests, FPB increased alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. In addition, FPB treatment increased cell viability on ethanol- and H₂O₂-induced HepG2 cells. FPB ameliorated serum biomarkers related to hepatoxicity including glutamic oxaloacetic transaminase, glutamine pyruvic transaminase, total bilirubin, and lactate dehydrogenase and lipid metabolism including triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Also, FPB controlled ethanol metabolism enzymes by regulating the protein expression levels of ADH, ALDH, and cytochrome P450 2E1 in liver tissue. FPB protected hepatic oxidative stress by improving malondialdehyde content, reduced glutathione, and superoxide dismutase levels. In addition, FPB reversed mitochondrial dysfunction by regulating reactive oxygen species production, mitochondrial membrane potential, and ATP levels. FPB protected ethanol-induced apoptosis, fatty liver, and hepatic inflammation through p-AMP-activated protein kinase and TLR-4/NF-κB signaling pathways. Furthermore, FPB prevented hepatic fibrosis by decreasing TGF-β1/Smad pathway. In summary, these results suggest that FPB might be a potential prophylactic agent for the treatment of alcoholic liver disease via preventing liver injury such as fatty liver, hepatic inflammation due to chronic ethanol-induced oxidative stress.

• Journal of Animal Science and Technology
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• v.66 no.5
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• pp.1021-1033
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• 2024

Exosomes have been extensively studied as disease biomarker in humans, given their role in transporting bioactive molecules. However, despite the great potential of exosomes as noninvasive diagnostic markers and therapeutic nanocarriers for bovine diseases, few studies have been conducted on bovine exosome. Thus, this study aimed to quantitatively and qualitatively compare three isolation methods to identify a suitable method for bovine serum. Exosomes were isolated using ultracentrifugation alone (UC), a combination of ultracentrifugation and size exclusion chromatography (US), or membrane affinity-based exoEasy kit (EE). Isolated particles were evaluated using a range of complementary techniques. Transmission electron microscopy showed that all three isolation methods resulted in particles with a cup-shaped morphology. The particle concentration measured by nanoparticle trafficking analyzer of US was lower compared to those of UC and EE method. As a result of immunoblotting, exosome markers including TSG101, CD81, and HSP70 were detected in US particles, while in UC and EE, only TSG101 expression was confirmed. Particles isolated from UC and EE showed a contamination with the blood protein albumin, whereas particles from US did not show albumin contamination. In addition, to evaluate the possibility of using exosomes as biomarkers, the profiles of the small RNA in the exosomes were compared using the bioanalyzer 2100. As a result, in the EE method, the band of small RNA (25-200 nt) was most prominent, and in the US methods, a distinct band was observed in the small RNA range. Collectively, the purity of exosomes without non-exosomal contamination was highest in the US method. However, for the detection of small RNA, the EE method was found to be the most suitable. Therefore, the results suggest that the optimal isolation method varies depending on the specific purpose of exosome isolation.

• Annals of Occupational and Environmental Medicine
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• v.34
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• pp.28.1-28.12
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• 2022

Background: Haenyeo is a woman who has the job of collecting seafood in the Jeju Sea at an average temperature of 13℃-14℃. The purpose of this study was to examine the cold acclimatization and occupational characteristics of Haenyeo through biomarkers such as orexin and irisin related to heat generation in the body. Methods: Twenty-one Haenyeo and 25 people with similar age, body type, and body mass index were selected as the control group (Control G). In the cold exposure experiment, a climate chamber was set to 5℃ and both feet were immersed in a 15℃ water tank for 30 minutes. Tympanic temperature (T_ty) and skin temperature (T_sk) were measured, and the mean body temperature (mT_b) was calculated. Blood samples were collected before and immediately after the examination. Orexin and irisin levels were analyzed. Results: Orexin levels were elevated after cold stimulation from 12.17 ± 4.44 to 12.95 ± 4.53 ng/mL (Haenyeo group [Haenyeo G], p < 0.01) and 10.37 ± 3.84 to 11.25 ± 4.02 ng/mL (Control G, p < 0.001). Irisin levels were elevated after cold stimulation from 4.83 ± 2.28 to 5.36 ± 2.23 ng/mL (Haenyeo G, p < 0.001) and 3.73 ± 1.59 to 4.18 ± 2.04 ng/mL (Control G, p < 0.001). The difference between Haenyeo G and Control G values in orexin and irisin appears not only in pre-exposure but also in post-exposure (p < 0.05). Conclusions: Our experimental results suggest that Haenyeo G were relatively superior in cold tolerance to Control G under cold exposure conditions. Haenyeo's cold acclimatization is due to the basic differences in pyrogens regarding body temperature control such as orexin and irisin. This means that Haenyeo are advantageous for cold survival.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.4
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• pp.363-374
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• 2022

Backgrounds/Aims: To analyze the results of the neoadjuvant treatment of patients in our center with early pancreatic cancer. Methods: Eighty-four patients with early pancreatic cancer (I-II) were included, of which 59 were considered "bioborderline" (carbohydrate antigen [CA] 19-9 > 37 U/L), and 25 were considered "non-bioborderline" (CA19-9 < 37 U/L). The R0 resection rate, presence of negative nodes, survival, and recurrence rates were analyzed in two groups, the NEO group (neoadjuvant + surgery) and the nonNEO group (upfront surgery). Results: A 28.6% pathologic complete response was observed in the NEO group of the whole sample. The residual R0 was 85.7%, and nodes were negative in 78.6% of the patients in the NEO group of bioborderline patients. All non-bioborderline patients treated with neoadjuvant were R0, and no affected nodes were observed in any of them. The median overall survival (OS) in patients with elevated CA19-9 levels in the NEO group was 31.4 months vs. 13.1 months in the non-NEO (log-rank test p = 0.006), with a 62% relative reduction in the mortality rate (hazard ratio = 0.38, 95% confidence interval: 0.20-0.79; p= 0.008). The median OS in patients with normal CA19-9 levels in the NEO group was 65.9 months vs. 16.2 months in the non-NEO group, without statistically significant differences between the two but with a trend toward significance (log-rank test p = 0.08). Conclusions: A neoadjuvant strategy seemed to improve local control and the survival of patients with early pancreatic cancer, both those with elevated CA19-9 and normal marker levels.

• Tuberculosis and Respiratory Diseases
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• v.87 no.4
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• pp.494-504
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• 2024

Background: Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer. Methods: Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated. Results: We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC. Conclusion: UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.50 no.3
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• pp.289-299
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• 2024

Chrysanthemum lucidum (C. lucidum), a perennial herb in the Asteraceae family, is an endemic species found only on Ulleung island in Gyeongsangbuk-do, South Korea. Previous studies have reported that the extract of C. lucidum exhibits excellent antioxidant activity due to its high polyphenol and flavonoid content. However, the anti-aging effects of C. lucidum extract, such as wrinkle improvement and cell regeneration, are not well known, and there has been no research on the activity of C. lucidum-derived extracellular vesicles (ClDEVs). Therefore, this study aimed to verify the anti-aging effects of ClDEVs through in vitro and clinical analyses. In cell experiments, ClDEVs promoted cell regeneration, increased the expression of COL1A1, a gene involved in collagen synthesis, and enhanced the expression of FLG and LOR, a biomarker related to skin barrier improvement. Additionally, ClDEVs suppressed the expression of aging-related biomarkers, such as the CDKN2A (encodes p16) and TP53 (encodes p53) genes, in cells induced to age. In a human clinical trial, after using a cosmetic product containing ClDEVs for 4 weeks, significant improvement in wrinkles around the eyes and nasolabial folds was observed. In conclusion, ClDEVs have demonstrated high potential as a bio-cosmetic ingredient for wrinkle improvement and anti-aging.

• Journal of Soil and Groundwater Environment
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• v.29 no.5
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• pp.27-36
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• 2024

This study, estimates the predicted no effect concentration (PNEC) for the protection of organisms in aquatic and soil environments, considering the mode of action of Perfluorooctanesulfonic acid (PFOS). PNECs were derived using the species sensitivity distribution (SSD) approach to estimate the hazardous concentration for 5% of species (HC5), with applying assessment factors. Chronic toxicity data on PFOS were collected through the USEPA's ECOTOX database and literature reviews, and classified by toxicity endpoints. PNECs were then derived for each of seven toxicity endpoints that met the criteria for SSD fitting. For aquatic organisms, the PNEC for PFOS, based on all available chronic toxicity data, was determined to be 0.53 ㎍/L. The PNECs for development, genetics, enzymes, growth, reproduction, population, and biochemical biomarkers were 0.28, 0.43, 0.83, 0.90, 2.17, 111.17, and 3.53 ㎍/L, respectively. The lowest PNEC was observed when the toxic endpoint was set as development, which is considered to be due to the mode of action of PFOS, known to cause developmental toxicity by disrupting the endocrine system of organisms. For soil organisms, toxicity data were insufficient to estimate PNECs for individual endpoints, so all available data were used to estimate a PNEC of 0.75 mg/kg. Estimating PNECs that consider the mode of action of contaminants is expected to reduce the likelihood of underestimating protection levels for environmental contaminants. Additionally, this study highlights the need for ecotoxicological assessments for individual toxicity endpoints of emerging contaminants, including Per- and polyfluoroalkyl substances, in soil environments.

• Journal of Nutrition and Health
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• v.53 no.3
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• pp.231-243
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• 2020

Purpose: To determine the metabolic influence of the traditional Korean diet (K-diet), which has been regarded as a healthy diet, we investigated the profile of urine organic acids that are intermediates of various types of metabolism including energy metabolism. Methods: Ten women aged 50-60 years were recruited and randomly divided into 2 diet groups, K-diet and control diet, the latter of which is a Westernized Korean diet that is commonly consumed by Koreans nowadays. Before and after the 2-week intervention, 46 urine organic acids were determined using LC/MS/MS, along with clinical parameters. Results: The average concentrations of succinate (4.14 ± 0.84 ㎍/mg creatinine vs. 1.49 ± 0.11, p = 0.0346) and hydroxymethylglutarate (3.67 ± 0.36 ㎍/mg creatinine vs. 2.97 ± 0.29, p = 0.0466), both of which are intermediates of energy metabolism, decreased in the K-diet group after the 2-week intervention, but these were not observed in the control diet group. In particular, the average concentration of succinate in the K-diet group was lower than that in the control group (3.33 ± 0.56 ㎍/mg creatinine vs. 1.49 ± 0.11, p = 0.0284) after 2 weeks. The concentrations of two tryptophan metabolites, 5-hydroxyindolacetate (3.72 ± 0.22 ㎍/mg creatinine vs. 3.14 ± 0.21, p = 0.0183) and indican (76.99 ± 8.35 ㎍/mg creatinine vs. 37.89 ± 10.06, p = 0.0205) also decreased only in the K-diet group. After the 2-week intervention, the concentration of kynurenate, another tryptophan metabolite, was lower in the K-diet group than that in the control diet group (3.96 ± 0.51 ㎍/mg creatinine vs. 2.90 ± 0.22, p = 0.0356). Interestingly, the urine level of kynurenate was positively correlated with BMI (r = 0.61424, p = 0.0003) and total cholesterol (r = 0.46979, p = 0.0088), which decreased only in the K-diet group (239.40 ± 15.14 mg/dL vs. 198.20 ± 13.25, p = 0.0163). Conclusion: The K-diet alters the urinary excretion of organic acids involved in energy metabolism and tryptophan metabolism, suggesting the influence of the K-diet on these types of metabolism. Urine organic acids changed by the K-diet may serve as biomarkers in future studies.