• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.284-290
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• 2023

Adefovir dipivoxil (ADV) is used for the treatment of hepatitis and acquired immunodeficiency syndrome, but long-term use can cause osteoporosis. In this study, the effect of ADV on the osteocyte maturation process was evaluated at the level of undifferentiated cells using mesenchymal stem cells (MSCs) and osteoblasts (MG63). First, MSCs and MG63 cells were treated with ADV at different concentrations, and then a Cell Counting Kit-8 analysis was performed to determine the effect on the proliferation of each cell. Additionally, crystal violet and Hoechst staining were performed for the morphological analysis of each cell and nucleus. To determine the cause of cell hypertrophy, the transforming growth factor-beta (TGF-β) expression was investigated, and alkaline phosphatase (ALP) staining and activity were measured to determine the degree of differentiation of the MSCs and MG63 cells into mature osteocytes. The results confirmed that the ADV increases the expression of TGF-β in MSCs and MG63 cells, causing cellular and nuclear hypertrophy, and can cause osteoporosis by inhibiting cell proliferation and affecting the differentiation of mature osteocytes. Therefore, it is believed that these results can be used as a basis for understanding the adverse effects of ADV at a cytological level in basic medicine and clinical research.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.306-313
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• 2023

Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β. Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.

• Korean Journal of Radiology
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• v.25 no.2
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• pp.166-178
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• 2024

Objective: This study aimed to determine the predictive performance of non-contrast CT (NCCT) signs for hemorrhagic growth after intracerebral hemorrhage (ICH) when stratified by onset-to-imaging time (OIT). Materials and Methods: 1488 supratentorial ICH within 6 h of onset were consecutively recruited from six centers between January 2018 and August 2022. NCCT signs were classified according to density (hypodensities, swirl sign, black hole sign, blend sign, fluid level, and heterogeneous density) and shape (island sign, satellite sign, and irregular shape) features. Multivariable logistic regression was used to evaluate the association between NCCT signs and three types of hemorrhagic growth: hematoma expansion (HE), intraventricular hemorrhage growth (IVHG), and revised HE (RHE). The performance of the NCCT signs was evaluated using the positive predictive value (PPV) stratified by OIT. Results: Multivariable analysis showed that hypodensities were an independent predictor of HE (adjusted odds ratio [95% confidence interval] of 7.99 [4.87-13.40]), IVHG (3.64 [2.15-6.24]), and RHE (7.90 [4.93-12.90]). Similarly, OIT (for a 1-h increase) was an independent inverse predictor of HE (0.59 [0.52-0.66]), IVHG (0.72 [0.64-0.81]), and RHE (0.61 [0.54-0.67]). Blend and island signs were independently associated with HE and RHE (10.60 [7.36-15.30] and 10.10 [7.10-14.60], respectively, for the blend sign and 2.75 [1.64-4.67] and 2.62 [1.60-4.30], respectively, for the island sign). Hypodensities demonstrated low PPVs of 0.41 (110/269) or lower for IVHG when stratified by OIT. When OIT was ≤ 2 h, the PPVs of hypodensities, blend sign, and island sign for RHE were 0.80 (215/269), 0.90 (142/157), and 0.83 (103/124), respectively. Conclusion: Hypodensities, blend sign, and island sign were the best NCCT predictors of RHE when OIT was ≤ 2 h. NCCT signs may assist in earlier recognition of the risk of hemorrhagic growth and guide early intervention to prevent neurological deterioration resulting from hemorrhagic growth.

• Korean Journal of Radiology
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• v.24 no.4
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• pp.349-361
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• 2023

Objective: To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. Materials and Methods: A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both non-contrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm² (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). Results: The number, area, and density of the subpleural small vessels increased after treatment by 35.7% (P < 0.001), 13.3% (P = 0.028), and 39.3% (P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio (P = 0.042). The BV5/TBV ratio was negatively correlated with PVR (r = -0.26; P = 0.035) and positively correlated with CI (r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP (r = -0.56; P = 0.001), PVR (r = -0.64; P < 0.001), and CI (r = 0.28; P = 0.049). Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I-IV (P = 0.004) and positively associated with 6MWD (P = 0.013). Conclusion: Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.

• Korean Journal of Radiology
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• v.24 no.11
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• pp.1102-1113
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• 2023

Objective: To elucidate the use of radiological studies, including nuclear medicine, and biopsy for the diagnosis and staging of prostate cancer (PCA) in clinical practice and understand the current status of PCA in Asian countries via an international survey. Materials and Methods: The Asian Prostate Imaging Working Group designed a survey questionnaire with four domains focused on prostate magnetic resonance imaging (MRI), other prostate imaging, prostate biopsy, and PCA backgrounds. The questionnaire was sent to 111 members of professional affiliations in Korea, Japan, Singapore, and Taiwan who were representatives of their working hospitals, and their responses were analyzed. Results: This survey had a response rate of 97.3% (108/111). The rates of using 3T scanners, antispasmodic agents, laxative drugs, and prostate imaging-reporting and data system reporting for prostate MRI were 21.6%-78.9%, 22.2%-84.2%, 2.3%-26.3%, and 59.5%-100%, respectively. Respondents reported using the highest b-values of 800-2000 sec/mm² and fields of view of 9-30 cm. The prostate MRI examinations per month ranged from 1 to 600, and they were most commonly indicated for biopsy-naïve patients suspected of PCA in Japan and Singapore and staging of proven PCA in Korea and Taiwan. The most commonly used radiotracers for prostate positron emission tomography are prostate-specific membrane antigen in Singapore and fluorodeoxyglucose in three other countries. The most common timing for prostate MRI was before biopsy (29.9%). Prostate-targeted biopsies were performed in 63.8% of hospitals, usually by MRI-ultrasound fusion approach. The most common presentation was localized PCA in all four countries, and it was usually treated with radical prostatectomy. Conclusion: This survey showed the diverse technical details and the availability of imaging and biopsy in the evaluation of PCA. This suggests the need for an educational program for Asian radiologists to promote standardized evidence-based imaging approaches for the diagnosis and staging of PCA.

• Korean Journal of Radiology
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• v.20 no.1
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• pp.83-93
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• 2019

Objective: The purpose of this study was to prospectively investigate the value of the myocardial extracellular volume fraction (ECV) in predicting myocardial functional outcome after revascularization of coronary chronic total occlusion (CTO). Materials and Methods: Thirty patients with CTO underwent cardiovascular magnetic resonance (CMR) before and 6 months after revascularization. Three baseline markers of functional outcome were evaluated in the dysfunctional segments assigned to the CTO vessels: ECV, transmural extent of infarction (TEI), and unenhanced rim thickness (RIM). At the global level, the ECV values of the whole myocardium with and without a hyperenhanced region (global and remote ECV) were respectively measured. Results: In per-segment analysis, ECV was superior to TEI and RIM in predicting functional recovery (area under receiver operating characteristic curve [AUC]: 0.86 vs. 0.75 and 0.73, all p values < 0.010), and it emerged as the only independent predictor of regional functional outcome (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.77-0.89; p < 0.001) independent of collateral circulation. In per-patient analysis, global baseline ECV was indicative of ejection fraction (EF) at the follow-up examination (β = -0.61, p < 0.001) and changes in EF (β = -0.57, p = 0.001) in multivariate regression analysis. A patient with global baseline ECV less than 30.0% (AUC, 0.93; sensitivity 94%, specificity 80%) was more likely to demonstrate significant EF improvement (OR: 0.38; 95% CI: 0.17-0.85; p = 0.019). Conclusion: Extracellular volume fraction obtained by CMR may provide incremental value for the prediction of functional recovery both at the segmental and global levels in CTO patients, and may facilitate the identification of patients who can benefit from revascularization.

• Animal Bioscience
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• v.37 no.1
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• pp.131-141
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• 2024

Objective: This experiment aimed to explore the protective action of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata on lipopolysaccharide (LPS)-induced liver injury in broilers. Methods: Total 216 healthy broilers were selected in a 21-d trial and assigned randomly to the following 3 treatments: control (CON) group, LPS group, and LPS+IA group. The CON and LPS groups were provided with a basal diet, whereas the LPS+IA group received the basal diet supplemented with 0.6 mg/kg Macleaya cordata IA. Broilers in LPS and LPS+IA groups were intraperitoneally injected with LPS (1 mg/kg body weight) at 17, 19, and 21 days of age, while those in CON group were injected with equivalent amount of saline solution. Results: Results showed LPS injection caused systemic and liver inflammation in broilers, inhibited immune function, and ultimately lead to liver injury. By contrast, supplementation of IA ameliorated LPS-induced adverse change in serum parameters, boosted immunity in LPS+IA group. Furthermore, IA suppressed the elevation of hepatic inflammatory cytokines and caspases levels induced by LPS, as well as the expressions of genes related to the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway. Conclusion: Dietary inclusion of 0.6 mg/kg Macleaya cordata IA could enhance immune function of body and inhibit liver damage via inactivating TLR4/MyD88/NF-κB signaling pathway in broilers.

• Journal of Korean Medicine for Obesity Research
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• v.23 no.2
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• pp.60-68
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• 2023

Objectives: This study was conducted to compare the effects of Hominis placenta (Jahage, J) and wild ginseng (SanSam, S) pharmacopuncture drugs on muscle differentiation and energy metabolism regulation in C2C12 myotubes. Methods: The C2C12 myoblasts were differentiated into myotubes for 5 days by replacing in medium containing 2% horse serum and then treated with J and S pharmacopuncture extract at different concentrations for 24 hr. The expression of myosin heavy chain and energy metabolism-regulating factors, myosin heavy chain (MHC), nuclear respiratory factor-1 (NRF-1), and proliferator-activated receptor γ coactivator-1 alpha (PGC-1α) were determined in C2C12 myotubes by western blot. Additionally, the phosphorylation of AMPK and the expression of mitochondrial biogenesis, including sirtuin 1 (SIRT1) were determined in the myotubes. Results: As a result, treatment with J and S pharmacopuncture extract at 0.1 and 1 mg/mL increased the MHC expression in C2C12 myotubes compared with non-treated cells, but only S pharmacopuncture was shown a significant and distinct increase in the expression. Expression of TFAM and NRF-1 was also shown significant increases in S and J pharmacopuncture in C2C12 myotubes compared to non-treated cells. The phosphorylation of AMPK and the expression of PGC-1α and SIRT1 showed increased expression in S and J pharmacopuncture compared to non-treated cells. The effect of low-dose of J pharmacopuncture on the phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and PGC-1α expression was greater than that of S pharmacopuncture. Conclusions: In conclusion, both J and S pharmacopuncture promote muscle differentiation in C2C12 myoblasts into myotubes and energy metabolism through the AMPK/SIRT1 signaling pathway. This indicates that the pharmacopuncture with tonic herbal medicines can help to improve skeletal muscle function.

• Korean Journal of Radiology
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• v.21 no.6
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• pp.764-772
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• 2020

Objective: Laser ablation is a therapeutic modality used to reduce the volume of large benign thyroid nodules. Unsatisfactory reduction and regrowth are observed in some treated nodules. The aim of the study was to evaluate the long-term outcomes of laser treatment for solid nodules during a 5-year follow-up period, the regrowth rate, and the predictive risk factors of nodule regrowth. Materials and Methods: We retrospectively evaluated patients with benign, solid, cold thyroid nodules who underwent laser ablation and were followed-up for 5 years. According to the selection criteria, 104 patients were included (median baseline nodule volume, 12.5 mL [25.0-75.0%, 8-18 mL]; median energy delivered, 481.5 J/mL [25.0-75.0%, 370-620 J/mL]). Nodule volume, thyroid function test results, and ultrasound were evaluated at baseline and then annually after the procedure. Results: Of 104 patients, 31 patients (29.8%) had a 12-month volume reduction ratio (VRR) < 50.0% and 39 (37.5%) experienced nodule regrowth. Of these 39 patients, 17 (43.6%) underwent surgery and 14 (35.9%) underwent a second laser treatment. The rate of nodule regrowth was inversely related to the 12-month VRR, i.e., the lower the 12-month VRR, the higher the risk of regrowth (p < 0.001). The mean time for nodule regrowth was 33.5 ± 16.6 months. The 12-month VRR was directly related to time to regrowth, i.e., the lower the 12-month VRR, the shorter the time to regrowth (p < 0.001; R² = 0.3516). Non-spongiform composition increased the risk of regrowth with an odds ratio of 4.3 (95% confidence interval [CI] 1.8-10.2; p < 0.001); 12-month VRR < 50.0% increased the risk of regrowth with an odds ratio of 11.7 (95% CI 4.2-32.2; p < 0.001). Conclusion: The VRR of thyroid nodules subjected to similar amounts of laser energy varies widely and depends on the nodule composition; non-spongiform nodules are reduced to a lesser extent and regrow more frequently than spongiform nodules. A 12-month VRR < 50.0% is a predictive risk factor for regrowth and correlates with the time to regrowth.

• Journal of Cardiovascular Imaging
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• v.31 no.3
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• pp.145-149
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• 2023

BACKGROUND: ¹⁸F-sodium fluoride positron emission tomography/computed tomography (¹⁸F-NaF PET/CT) has been proven to be useful in identification of microcalcifications, which are stimulated by inflammation. Blood speckle imaging (BSI) is a new imaging technology used for tracking the flow of blood cells using transesophageal echocardiography (TEE). We evaluated the relationship between turbulent flow identified by BSI and inflammatory activity of the aortic valve (AV) as indicated by the ¹⁸F-NaF uptake index in moderate aortic stenosis (AS) patients. METHODS: This study enrolled 18 moderate AS patients diagnosed within the past 6 months. BSI within the aortic root was acquired using long-axis view TEE. The duration of laminar flow and the turbulent flow area ratio were calculated by BSI to demonstrate the degree of turbulence. The maximum and mean standardized uptake values (SUVmax, SUVmean) and the total microcalcification burden (TMB) as measured by ¹⁸F-NaF PET/CT were used to demonstrate the degree of inflammatory activity in the AV region. RESULTS: The mean SUVmean, SUVmax, and TMB were 1.90 ± 0.79, 2.60 ± 0.98, and 4.20 ± 2.18 mL, respectively. The mean laminar flow period and the turbulent area ratio were 116.1 ± 61.5 msec and 0.48 ± 0.32. The correlation between SUVmax and turbulent flow area ratio showed the most positive and statistically significant correlation, with a Pearson's correlation coefficient (R²) of 0.658 and a p-value of 0.014. CONCLUSIONS: The high degree of trans-aortic turbulence measured by BSI was correlated with severe AV inflammation.