• Korean Journal of Environmental Biology
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• v.42 no.1
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• pp.1-14
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• 2024

This study evaluated the risk of single and combined exposure to microplastics in zebrafish (Danio rerio) through biomarkers, such as survival rate, excretion rate, and histological alterations of organ systems. The experimental groups were the control(Cont.), single microplastics exposure group(MPs, 1.83%/fish total weight(g)), the copper group(Cu, 21.6 ㎍ L^-1), and a group with combined exposure to MPs and copper (MPs^*Cu). The experiment was conducted with individual exposure (7 days) for MP excretion rate analysis and group exposure (14 days) for biomarker analysis. The daily excretion rate of MPs tended to decrease in a time-dependent manner. The copper concentration in the body was not significantly different between single and combined copper exposure. The degeneration of mucous cells in the skin, capillary dilation of the gill lamella, increased intestinal mucous, hepatocyte hypertrophy, and the degeneration of glomeruli and renal tubules were observed in all exposure groups. These histological alterations showed the highest tendency in the MPs^*Cu group. In this study, the changes in biomarkers were attributed to the single effect of copper or the combined effect of copper and MPs rather than being solely influenced by MPs.

• 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.

• Molecules and Cells
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• v.45 no.5
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• pp.343-352
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• 2022

The advent of the assay for transposase-accessible chromatin using sequencing (ATAC-seq) has shown great potential as a leading method for analyzing the genome-wide profiling of chromatin accessibility. A comprehensive reference to the ATAC-seq dataset for disease progression is important for understanding the regulatory specificity caused by genetic or epigenetic changes. In this study, we present a genome-wide chromatin accessibility profile of 44 liver samples spanning the full histological spectrum of nonalcoholic fatty liver disease (NAFLD). We analyzed the ATAC-seq signal enrichment, fragment size distribution, and correlation coefficients according to the histological severity of NAFLD (healthy control vs steatosis vs fibrotic nonalcoholic steatohepatitis), demonstrating the high quality of the dataset. Consequently, 112,303 merged regions (genomic regions containing one or multiple overlapping peak regions) were identified. Additionally, we found differentially accessible regions (DARs) and performed transcription factor binding motif enrichment analysis and de novo motif analysis to determine new biomarker candidates. These data revealed the gene-regulatory interactions and noncoding factors that can affect NAFLD progression. In summary, our study provides a valuable resource for the human epigenome by applying an advanced approach to facilitate diagnosis and treatment by understanding the non-coding genome of NAFLD.

• The Korean Journal of Malacology
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• v.29 no.1
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• pp.33-41
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• 2013

This study investigated concentration of metal ions, intersexuality and histological alterations of digestive gland in Mytilus galloprovincialis. Samples were collected from two areas of Gamak Bay in May, 2010. The concentration of metal ions showed that Al ($366.5{\pm}249.7$ mg/kg) was highest and Zn ($179.5{\pm}67.8$ mg/kg) was second high concentration. Co ($1.0{\pm}0.2$ mg/kg) was lowest. The intersexuality was 26.4% and males (38.8%) was higher than the females (12.9%). Intersex type was observed four types. Destruction of digestive tubule epithelium was highest among other biomarker in digestive gland. Distribution of basophilic cell and lipofuscin was 6.1% and 1.5%, respectively.

• Ocean and Polar Research
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• v.25 no.2
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• pp.147-154
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• 2003

To develop fast and sensitive biomarkers for metal exposures in Antarctic marine organisms we examined histological alterations of an Antarctic sentinel bivalve species Laternula elliptica following a short-term exposure to a sublethal-level of Cd. Distinct histological alterations of tissues and cells of the gills, kidneys, and digestive glands were observed after 8-to 16-hours of exposure to Cd while an increase of Cd concentrations in tissues was not detectable. Most alterations were highly localized in the epithelium of the three tissues; epithelia were found to be detached from the remaining tissue parts. In addition ultra-structural changes such as cytosolic vacuolization, dilation of nucleus and rER membranes were detected in all three tissues, which suggested that the clams are subject to sublethal stresses. Thus, histological and ultrastructural changes on localized tissue parts were rapid and sensitive, suggesting that they may serve biomarkers for Cd exposures. Linkages between the shown ulrastructural changes and higher biological organization level responses are to be established by longer-term exposure experiments.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2133-2137
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• 2012

Objective: To investigate the prognostic role of antigen KI-67 (Ki-67) and G1/S-specific cyclin-D1 (cyclin-D1) in patients with laryngeal squamous cell carcinoma (LSCC). Methods: Immunohistochemical staining (IHS) was used to determine the protein expression of Ki-67 and cyclin-D1 in LSCC tissues. Kaplan-Meier survival curves was calculated with reference to Ki-67 and cyclin-D1 levels. Results: Cyclin-D1 and Ki67 were expressed in the nuclei of cancer cells. Among the total of 92 cancer tissues examined by immunohistochemistry, 60 (65.22%) had cyclin-D1 overexpression and 56 (60.87%) had Ki67 overexpression. Cyclin-D1 overexpression is associated with the advanced stage of the cancer (P=0.029), but not with gender, age, stage of cancer, histological differentiation, anatomical site, smoking history and alcohol consumption history. Ki67 overexpression is not associated with the advanced stage, gender, age, histological differentiation, anatomical site, smoking history and alcohol consumption history. A statistically significant correlation was found between lymph node status and the expression of Ki67 (p = 0.025). Overexpression of cyclin-D1 was correlated to shorter relapse-free survival period (P<0.001). Conclusions: Overexpression of cyclin-D1 can be used as a marker to predict relapse in patients with LSCC after primary curative resection.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.747-751
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• 2015

Background: Stage III colon cancer patients demonstrate diverse clinical outcomes. The aim of this study was to develop a prognostic model in order to better predict their survival. Materials and Methods: From 2004 to 2010, 548 patients were retrospectively analyzed, among whom 328 were defined as the study group and the remaining 220 served as a validation group. Clinico-pathologic features, including age, gender, histological grade, T stage, number of positive lymph nodes, number of harvest lymph nodes, pretreatment carcinoembryonic antigen (CEA) levels and pretreatment neutrophil lymphocyte ratio (NLR), were collected. Kaplan-Meier survival curves were used to detect prognostic factors and multivariate analysis was applied to identify independent examples on which to develop a prognostic model. Finally, the model was further validated with the validation group. Results: Histological grade (p=0.002), T stage (p=0.011), number of positive lymph nodes (p=0.003), number of harvested lymph nodes (p=0.020), CEA (p=0.005), and NLR (p<0.001) were found as prognostic factors while histological grade [RR(relative risk):0.632, 95%CI (Confidence interval) 0.405~0.985, p=0.043], CEA (RR:0.644, 95%CI:0.431~0.964, p=0.033) and NLR (RR:0.384, 95%CI:0.255~0.580, p<0.001) levels were independent. The prognostic model based on these three factors was able to classify patients into high risk, intermediate and low risk groups (p<0.001), both in study and validation groups. Conclusions: Histological grade, pretreatment CEA and NLR levels are independent prognostic factors in stage III colon cancer patients. A prognostic model based on these factors merits attention in future clinical practice.

• Journal of Korean Medicine Rehabilitation
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• v.29 no.2
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• pp.115-133
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• 2019

Objectives The purpose of this study was to evaluate the effects of Curcumae Longae Rhizoma pharmacopuncture on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods Osteoarthritis was induced by injection of MIA ($50{\mu}L$ with 80 mg/mL) into knee joint cavity of rats. Rats were divided into 6 groups. Normal group was injected by normal saline into knee joint cavity only. Control group was induced for osteoarthritis by MIA and orally administered with distilled water. Normal Saline group was induced for osteoarthritis by MIA and injected with normal saline $100{\mu}L$. Positive comparison group was injected with MIA and orally administered with indomethacin 5 mg/kg. Curcumae Longae Rhizoma pharmacopuncture low concentration (CL) group was induced for osteoarthritis by MIA and injected with Curcumae Longae Rhizoma pharmacopuncture low concentration $100{\mu}L$. Curcumae Longae Rhizoma pharmacopuncture high concentration (CH) group was induced for osteoarthritis by MIA and injected with Curcumae Longae Rhizoma pharmacopuncture high concentration $100{\mu}L$. Curcumae Longae Rhizoma pharmacopuncture was injected at ST35 and EX-LE4 each group (CL, CH). After that, hind paw weight distribution was measured and oxidative stress biomarker in serum, liver function biomarker in serum, western blot analysis were measured. Histological analysis of knee joint tissue was performed by hematoxylin and eosin staining, Safranin-O staining and Masson's trichrome staining. Results Hind paw weight distribution was significantly improved in both group. alanine aminotransferanse and aspartate aminotransferase were decreased significantly in CH group compare with Indomethacin threated group. Antioxidant enzyme glutathione peroxidase, Catalase and heme oxygenase-1 were increased in CH group compare with control group. Inflammatory cytokine cyclooxygenase-2, inducible nitric oxide synthase and interleukin-1 beta were decreased significantly in CH group. Histological analysis result shows that protective effects of joint and cartilage were observed in both CH and CL groups in a concentration-dependent. Conclusions The result suggest that Curcumae Longae Rhizoma pharmacopuncture has anti-oxidation effect, anti-inflammatory effect and also can prevent progression of osteoarthritis and protect joint cartilage.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.513-517
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• 2015

Background: Growing evidence suggests that the members of the ubiquitin-proteasome system (UPS) are important for tumorigenesis. HERC4, one component, is a recently identified ubiqutin ligase. However, the expression level and function role of HERC4 in lung cancer remain unknown. Our objective was to investigate any correlation between HERC4 and development of lung cancer and its clinical significance. Materials and Methods: To determine HERC4 expression in lung cancer, an immunohistochemistry analysis of a tissue microarray containing samples of 10 lung normal tissues, 15 pulmonary neuroendocrine carcinomas, 45 squamous epithelial cancers and 50 adenocarcinomas was conducted. Receiver operating characteristic (ROC) curve analysis was applied to obtain a cut-off point of 52.5%, above which the expression of HERC4 was regarded as "positive". Results: On the basis of ROC curve analysis, positive expression of HERC4 was detected in 0/10 (0.0%) of lung normal tissues, in 4/15 (26.7%) of pulmonary neuroendocrine carcinomas, in 13/45 (28.9%) of squamous epithelial cancers and in 19/50 (38.0%) of adenocarcinomas. It showed that lung tumors expressed more HERC4 protein than adjacent normal tissues (${\chi}^2$=4.675, p=0.031). Furthermore, HERC4 positive expression had positive correlation with pT status (${\chi}^2$=44.894, p=0.000), pN status (${\chi}^2$=43.628, p=0.000), histological grade (${\chi}^2$=7.083, p=0.029) and clinical stage (${\chi}^2$=72.484, p=0.000), but not age (${\chi}^2$=0.910, p=0.340). Conclusions: Our analysis suggested that HERC4 is likely to be a diagnostic biomarker for lung cancer.

• Korean Journal of Environmental Biology
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• v.38 no.4
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• pp.678-690
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• 2020

In this study, the histological changes of Zacco platypus exposed to discharge from a Wastewater Treatment Plant (WTP), which is a point source, for a long time (2 to 3 years) were compared to the same species at a reference site (Ref.). Overall, tissues displayed various lesions in samples obtained at the point where discharge water from the point source was mixed. In the skin tissue, mucus cells from the epithelial layer expanded to the multilayered epithelium, indicating the immune system was activated. Epithelial cell detachment and proliferation were most prominent in the gills, which may have adversely affected circulation and respiration. Our data suggest immune system collapse was due to stimulation by aquatic substances. Both the fish phase analysis and the water quality analysis demonstrated depreciated conditions at the point source as compared to the reference stream, supporting the histological health evaluation results. These data together suggest a histological approach can also be used to assess water quality, and to an even higher degree when combined with other existing methods. Given the presented evaluation, improvement in the water quality of water discharged from WTP's is required.