• IMMUNE NETWORK
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• v.6 no.3
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• pp.154-162
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• 2006

Background: Dendritic cell (DC)-based cancer immunotherapy is studied for several years. However, it is mainly derived from autologous PBMC or leukapheresis from patient, which has limitations about yield and ability of DC production according to individual status. In order to solve these problems, inquiries about allogeneic DCs are performed but there are no preclinical trial answers for effect or toxicity of allogeneic DC to use for clinical trial. In this study, we compared the anti-tumor effect of allogeneic and autologous DCs from mouse bone marrow stem cells in mouse metastatic melanoma model. Methods: B16F10 melanoma cells ($5{\times}10^4$/mouse) were injected intravenously into the C57BL/6 mouse. Therapeutic DCs were differentiated from autologous (C57BL/6: CDC) or allogeneic (B6C3F1: BDC) bone marrow stem cells with GM-CSF, SCF and IL-4 for 13days and pulsed with B16F10 tumor cell lysate (Blys) for 18hrs. DC intra-peritoneal injections began on the 8th day after the tumor cell injection by twice with one week interval. Results: Anti-tumor response was observed by DC treatment without any toxicity especially in allogeneic DC treated mice (tumor burden score: $2.667{\pm}0.184,\;2.500{\pm}0.463,\;2.000{\pm}0.286,\;1.500{\pm}0.286,\;1.667 {\pm}0.297$ for saline, CDC/unpulsed-DC: U-DC, CDC/Blys-DC, BDC/U-DC and BDC/Blys-DC, respectively). IFN-${\gamma}$ secretion was significantly increased in allogeneic DC group stimulated with B16F10 cell lysate ($2,643.3{\pm}5,89.7,\;8,561.5{\pm}2,204.9.\;6,901.2{\pm}141.1pg/1{\times}10^6$ cells for saline, BDC/U-DC and BDC/Blys-DC, respectively) with increased NK cell activity. Conclusion: Conclusively, promising data was obtained that allogeneic DC can be used for DC-based cancer immunotherapy.

• Korean Journal of Food Science and Technology
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• v.45 no.3
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• pp.356-363
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• 2013

Clinical and preclinical trials of involving drugs with anti-obesity effects have focused on screening for herbal medicines suspected to have anti-obesity activities. In this study, an extract of Aster scaver Thunb., which was prepared in 80% methanol (ASE), was assessed for its total phenol content, total flavonoid content, antioxidant activity ability to scavenge the ${\alpha}-{\alpha}$-diphenyl-${\beta}$-picrylhydrazyl, 2,2'-azino-bis-[3-ethylbenzthiazoline]-6-sulfonic acid radical, and anti-adipogenic effects. The anti-adipogenic effect of ASE on the differentiation of 3T3-L1 pre-adipocytes to adipocytes was investigated by assaying the suppression of adipocyte differentiation and lipid accumulation by using western blot analysis and the Oil Red-O assay, respectively. The staining results showed that ASE significantly inhibited 3T3-L1. Western blot analysis results showed that ASE decreased the levels of peroxisome proliferator-activated receptor-${\gamma}$, CCAAT/enhancer-binding protein ${\alpha}$, and sterol regulatory element-binding protein 1c. These results demonstrate that ASE directly inhibits the differentiation of preadipocytes, and might be an important adjunct in the therapeutic efforts to reduce adipogenesis.

• Journal of Animal Science and Technology
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• v.58 no.2
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• pp.6.1-6.11
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• 2016

Background: Dietary supplementation of unsaturated fats in ruminants, if not stabilized, can instigate oxidative stress which can have negative impact on production performance and enhance the susceptibility to various diseases. The current study examined the effect of dietary 80 % canola oil and 20 % palm oil blend (CPOB) on serum fatty acids, antioxidant profile and biochemical indices in goats. Thirty Boer bucks (4-5 months old; initial BW, $20.34{\pm}0.77kg$) were randomly assigned to diets containing 0, 4 or 8 % CPOB and fed daily for a period of 90 days. Blood was sampled from the goats on 0, 30, 60 and 90 days of the trial and the serum was analyzed for fatty acids, cholesterol, glucose, total protein, antioxidants and lipid oxidation. Results: Neither diet nor sampling time influenced serum TBARS value, catalase, glutathione peroxidase and superoxide dismutase activities, LDL cholesterol, VLDL cholesterol, triglycerides, glucose and total protein. Goats fed 4 and 8 % CPOB had higher (P < 0.05) total cholesterol and HDL cholesterol than the control goats on day 30, 60 and 90. The proportion of C15:0 decreased with increasing level of CPOB on day 30 and 60. Serum C18:1n-9 increased with increasing level of CPOB in diet on day 60. The proportion of C18:3n-3 and C22:5n-3 increased (P < 0.05), while the proportion of C18:2n-6 decreased (P < 0.05) with increase in the level of CPOB on day 60 and 90. Dietary CPOB did not affect serum total carotenoid and ${\delta}$-tocopherol but did increase (P < 0.05) ${\alpha}$ and ${\gamma}$-tocopherol. Conclusion: Dietary canola oil and palm oil blend could be supplemented in diets without instigating oxidative stress in goats.

• Korean Journal of Head & Neck Oncology
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• v.35 no.2
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• pp.19-25
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• 2019

Background/Objectives: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the deadliest forms of thyroid cancer. The fatality rate for ATC is high, and the survival rate at one year after diagnosis is <20%. The present study aimed to investigate the anti-tumor activities of paclitaxel, radiation, and tyrosine kinase inhibitor (TKI) combined therapy in anaplastic thyroid cancer cells both in vitro and in vivo and explore its effects on apoptotic cell death pathways. Materials & Methods: ATC cell line was exposed to TKI, lenvatinib in the presence or absence of paclitaxel with radiation, and cell viability was determined by MTT assay. Effects of the combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell line xenograft model was used to examine the anti-tumor activity in vivo. Results: Our data revealed that the combined administration of paclitaxel, TKI, and radiation decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as demonstrated by the cleavage of caspase-3 and DNA fragmentation. This combination therapy reduced anti-apoptotic factor levels in ATC cells, while significantly decreasing tumor volume and increasing survival in ATC xenografts. Conclusion: These results indicate that administering the combination of paclitaxel, TKI, and radiation therapy may exert significant anticancer effects in preclinical models, potentially suggesting a new clinical approach for treating patients with ATC.

• Toxicological Research
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• v.30 no.4
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• pp.305-309
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• 2014

Recently, there has been an increase in the use of several nephrotoxicity biomarkers in preclinical experiments. In addition, it has been indicated that the result may have been influenced by secondary factors, such as sample storage condition or storage period. In this study, we have assessed the variation in urinary nephrotoxicity biomarkers as a result of urine storage conditions and storage period of the urine. Urine was sampled from specific pathogen-free Sprague-Dawley rats (19 weeks old), which were housed individually in hanged stainless steel wire mesh cages. Urine was stored at $20^{\circ}C$, at $4^{\circ}C$, or at $-70^{\circ}C$ after sampling. The levels of the biomarkers such as beta-2 microglobulin (B2M), cystatin-C (Cys-C), N-acetyl-${\beta}$-D-glucosaminidase (NAG), micro albumin (MA), micro protein (MP) were measured at 6, 24, 48 and 144 hr after sampling. The B2M level was significantly decreased at 6, 24, 48, and 144 hr compared to 0 hr at $-70^{\circ}C$ (p < 0.05, p < 0.01, p < 0.05, and p < 0.05, respectively) and 24 and 144 hr at $20^{\circ}C$ (p < 0.01, p < 0.01, respectively). The Cys-C level was significantly decreased at 144 hr compared to 0 hr at $4^{\circ}C$ (p < 0.01), at $20^{\circ}C$ (p < 0.05) and at $70^{\circ}C$ (p < 0.01). MP and MA levels were not different for 144 hr in all storage conditions. Taken together, B2M and Cys-C levels were modulated by storage temperature and period. For the enhancement of test accuracy, it is suggested that strict protocols be established for samples to minimize the effects of the storage conditions on the detected levels of biomarkers.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.45 no.2
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• pp.97-107
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• 2019

Objectives: Small animal maxillofacial models, such as non-segmental critical size defects (CSDs) in the rabbit mandible, need to be standardized for use as preclinical models of bone regeneration to mimic clinical conditions such as maxillofacial trauma. The objective of this study is the establishment of a mechanically competent CSD model in the rabbit mandible to allow standardized evaluation of bone regeneration therapies. Materials and Methods: Three sizes of bony defect were generated in the mandibular body of rabbit hemi-mandibles: $12mm{\times}5mm$, $12mm{\times}8mm$, and $15mm{\times}10mm$. The hemi-mandibles were tested to failure in 3-point flexure. The $12mm{\times}5mm$ defect was then chosen for the defect size created in the mandibles of 26 rabbits with or without cautery of the defect margins and bone regeneration was assessed after 6 and 12 weeks. Regenerated bone density and volume were evaluated using radiography, micro-computed tomography, and histology. Results: Flexural strength of the $12mm{\times}5mm$ defect was similar to its contralateral; whereas the $12mm{\times}8mm$ and $15mm{\times}10mm$ groups carried significantly less load than their respective contralaterals (P<0.05). This demonstrated that the $12mm{\times}5mm$ defect did not significantly compromise mandibular mechanical integrity. Significantly less (P<0.05) bone was regenerated at 6 weeks in cauterized defect margins compared to controls without cautery. After 12 weeks, the bone volume of the group with cautery increased to that of the control without cautery after 6 weeks. Conclusion: An empty defect size of $12mm{\times}5mm$ in the rabbit mandibular model maintains sufficient mechanical stability to not require additional stabilization. However, this defect size allows for bone regeneration across the defect. Cautery of the defect only delays regeneration by 6 weeks suggesting that the performance of bone graft materials in mandibular defects of this size should be considered with caution.

• Journal of Life Science
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• v.32 no.10
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• pp.812-820
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• 2022

Depression is a psychiatric disorder characterized by depressed mood, anhedonia, fatigue, and altered cognitive function, leading to a decline in daily functioning. In addition, depression is a serious and common mental illness not only in an individual's life but also in society, so it must be actively treated. Autophagy is involved in the pathophysiological mechanism of mental illness. According to a recent study, it is known that autophagy-induced apoptosis affects neuroplasticity and causes depression and that antidepressants regulate autophagy. Autophagy is a catabolic process that degradation and removes unnecessary organelles or proteins through a lysosome. And, it is essential for maintaining cellular homeostasis. Autophagy is activated in stress conditions, and depression is a stress-related disease. Stress causes damage to cellular homeostasis. Recently, although the role of autophagy mechanisms in neurons has been investigated, the autophagy of depression has not been fully studied. This review highlights the new evidence for the involvement of autophagy in the pathophysiological mechanisms and treatment of depression. To highlight the evidence, we present results from clinical and preclinical studies showing that autophagy is associated with depression. Understanding the relevance of autophagy to depression and the limitations of research suggest that autophagy regulation may provide a new direction for antidepressant development.

• Journal of Korean Neurosurgical Society
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• v.65 no.5
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• pp.665-679
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• 2022

Objective : Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. Methods : We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. Results : Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. Conclusion : PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

• Journal of Periodontal and Implant Science
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• v.53 no.2
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• pp.120-134
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• 2023

Purpose: We investigated whether repeated irradiation with light-emitting diodes (LEDs) at a combination of 470 nm and 525 nm could suppress the progression of experimental periodontitis. Methods: A experimental periodontitis model was established in the second, third, and fourth premolars of the mandible in beagle dogs for 2 months. The spontaneous progression of periodontitis was monitored under the specified treatment regimen for 3 months. During this period, the animals were subjected to treatments of either plaque control only (control) or plaque control with LED application (test) at 2-week intervals. The clinical parameters included the probing pocket depth (PPD), gingival recession (GR), and the clinical attachment level (CAL). Histomorphometric analysis was performed using measurements of the length of the junctional epithelium, connective tissue (CT) zone, and total soft tissue (ST). Results: There were significant differences in PPD between the control and test groups at baseline and 12 weeks. When the change in PPD was stratified based on time intervals, it was shown that greater differences occurred in the test group, with statistical significance for baseline to 12 weeks, 6 to 12 weeks, and baseline to 6 weeks. There was no significant difference in GR between the control and test groups at any time points. Likewise, no statistically significant differences were found in GR at any time intervals. CAL showed a statistically significant difference between the control and test groups at baseline only, although significant differences in CAL were observed between baseline and 12 weeks and between 6 and 12 weeks. The proportion of CT to ST was smaller for both buccal and lingual areas in the control group than in the test group. Conclusions: Repeated LED irradiation with a combination of 470-nm and 525-nm wavelengths may help suppress the progression of periodontal disease.

• Journal of health informatics and statistics
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• v.41 no.1
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• pp.49-56
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• 2016

Objectives: Carotid intima-media thickness (CIMT) and the presence of carotid artery plaque are widely used as preclinical markers of atherosclerosis. Due to operator dependency in measuring CIMT, it is important to evaluate the reliability of measuring CIMT and plaque between centers in a multicenter study. The purpose of this study is to evaluate the inter-rater reliability of CIMT and plaque presence among three clinical centers of the Cardiovascular and Metabolic Disease Etiology Research Center (CMERC). Methods: Twenty people without known cardiovascular disease (age 37-64) were enrolled during 2014-2015, and their left and right carotid arteries were examined repeatedly with ultrasonography for CIMT measurements at three clinical centers according to a predetermined protocol. Maximum and mean values of CIMT at distal common carotid artery were recorded. Plaque presence at a carotid artery was checked by an operator. The reliability of CIMT and carotid plaque presence was assessed using an intraclass correlation coefficient (ICC) and kappa statistics, respectively. Results: Calculated ICC was 0.647 (95% CI: 0.487-0.779) for maximum CIMT, and 0.758 (95% CI: 0.632- 0.854) for mean CIMT. In Bland Altman plot, most observed values were distributed within mean difference ${\pm}1.96$ SD ranges. Kappa statistics of plaque presence between two centers were 0.304 (center 1 and 2), 0.507 (center 1 and 3), and 0.606 (center 2 and 3), respectively, while Fleiss kappa for overall agreement was 0.445. Conclusions: The inter-rater reliability of CIMT measurements among three clinical centers turned out to be high, and the agreement of measuring carotid plaque presence was fair.