• Journal of Animal Science and Technology
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• 제58권2호
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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.

• 대한두경부종양학회지
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• 제35권2호
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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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• 제30권4호
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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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• 제45권2호
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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.

• 생명과학회지
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• 제32권10호
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• pp.812-820
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• 2022

우울증은 우울한 기분, 무쾌감증, 피로 및 인지 기능 변화를 특징으로 하는 정신질환으로 일상 기능의 저하를 초래한다. 또한, 우울증은 개인의 삶뿐만 아니라 사회적으로도 심각하고 흔한 정신질환이므로 적극적인 치료가 필요하다. 자가소화작용은 정신질환의 병태생리학적 기전에 관여한다. 최근 연구에 따르면, 자가소화작용에 의한 세포사멸이 신경가소성에 영향을 주어 우울증을 유발하고, 항우울제가 자가소화작용을 조절한다고 알려져 있다. 자가소화작용은 용해소체를 통해 불필요한 세포소기관이나 단백질을 분해하고 제거하는 이화과정이다. 그리고, 세포의 항상성을 유지하는데 필수적이다. 자가소화작용은 스트레스 상황에서 활성화되며 우울증은 스트레스 관련 질병이다. 최근, 신경세포에서 자가소화작용 기전의 역할이 조사되고 있지만, 우울증의 자가소화작용은 완전히 연구되지 않았다. 이 리뷰에서 우울증의 병태생리학적 기전과 치료에 자가소화작용이 관여한다는 새로운 증거를 강조하고자 한다. 증거를 강조하기 위해 자가소화작용이 우울증과 관련되어 있음을 보여주는 임상 및 전임상 연구결과들을 소개한다. 우울증에 대한 자가소화작용의 관련성과 연구의 한계를 이해하는 것은 자가소화작용 조절이 항우울제 개발의 새로운 방향을 제공할 것으로 사료된다.

• Journal of Korean Neurosurgical Society
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• 제65권5호
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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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• 제53권2호
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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 Korean Neurosurgical Society
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• 제67권5호
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• pp.510-520
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• 2024

Objective : Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The treatment of PD aims to alleviate motor symptoms by replacing the reduced endogenous dopamine. Currently, there are no disease-modifying agents for the treatment of PD. Zebrafish (Danio rerio) have emerged as an effective tool for new drug discovery and screening in the age of translational research. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain, with corresponding Parkinsonian symptoms. L-type calcium channels (LTCCs) have been implicated in the generation of mitochondrial oxidative stress, which underlies the pathogenesis of PD. Therefore, we investigated the neuro-restorative effect of LTCC inhibition in an MPTP-induced zebrafish PD model and suggested a possible drug candidate that might modify the progression of PD. Methods : All experiments were conducted using a line of transgenic zebrafish, Tg(dat:EGFP), in which green fluorescent protein (GFP) is expressed in dopaminergic neurons. The experimental groups were exposed to 500 μmol MPTP from 1 to 3 days post fertilization (dpf). The drug candidates : levodopa 1 mmol, nifedipine 10 μmol, nimodipine 3.5 μmol, diethylstilbestrol 0.3 μmol, luteolin 100 μmol, and calcitriol 0.25 μmol were exposed from 3 to 5 dpf. Locomotor activity was assessed by automated tracking and dopaminergic neurons were visualized in vivo by confocal microscopy. Results : Levodopa, nimodipine, diethylstilbestrol, and calcitriol had significant positive effects on the restoration of motor behavior, which was damaged by MPTP. Nimodipine and calcitriol have significant positive effects on the restoration of dopaminergic neurons, which were reduced by MPTP. Through locomotor analysis and dopaminergic neuron quantification, we identified the neuro-restorative effects of nimodipine and calcitriol in zebrafish MPTP-induced PD model. Conclusion : The present study identified the neuro-restorative effects of nimodipine and calcitriol in an MPTP-induced zebrafish model of PD. They restored dopaminergic neurons which were damaged due to the effects of MPTP and normalized the locomotor activity. LTCCs have potential pathological roles in neurodevelopmental and neurodegenerative disorders. Zebrafish are highly amenable to high-throughput drug screening and might, therefore, be a useful tool to work towards the identification of disease-modifying treatment for PD. Further studies including zebrafish genetic models to elucidate the mechanism of action of the disease-modifying candidate by investigating Ca2+ influx and mitochondrial function in dopaminergic neurons, are needed to reveal the pathogenesis of PD and develop disease-modifying treatments for PD.

• Journal of health informatics and statistics
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• 제41권1호
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• pp.49-56
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• 2016

목적: 경동맥 내막-중막 두께와 경동맥 경화반의 존재유무는 죽상동맥경화증의 임상 전단계를 나타내는 지표로 널리 사용되고 있다. 경동맥 내막-중막 두께를 측정할 때의 측정자 의존성 때문에, 다기관 연구에서는 경동맥 내막-중막 두께와 경화반 측정의 기관간 신뢰도를 확인하는 것이 중요하다. 이 연구의 목적은 심뇌혈관 및 대사질환원인 연구센터에 속해 있는 세 임상기관 사이의 경동맥 내막-중막 두께와 경화반 측정의 측정자간 신뢰도를 평가하는 것이다. 방법: 심뇌혈관 질환 과거력이 없는 사람 20명이 2014-2015년 사이에 이 연구에 참여하였고(연령 37-64세), 미리 정해진 프로토콜에 따라 연구참여자의 좌, 우 경동맥을 세 임상기관에서 반복적으로 측정하였다. 총 경동맥의 원위부에서 측정한 경동맥 내막-중막 두께의 최대값과 평균값을 기록하였다. 경동맥에서의 경화반 존재유무는 측정자에 의해 확인되었다. 경동맥 내막-중막 두께와 경화반 존재유무의 신뢰도를 급내상관계수와 카파 통계량을 통해 각각 평가하였다. 결과: 계산된 급내상관계수는 최대 경동맥 내막-중막 두께를 평가하였을 때 0.647이었고 (95% CI: 0.487-0.779), 평균 경동맥 내막-중막 두께를 평가하였을 때 0.758 (95% CI: 0.632-0.854) 이었다. Bland Altman plot에서, 관측치의 대부분은 평균의 차이에서 ${\pm}1.96$ 표준편차 사이에 분포하였다. 각 기관 사이의 경화반 존재유무에 대한 카파 통계량은 0.304 (기관 1과 2), 0.507 (기관 1과 3), 0.606 (기관 2와 3)이었다. 전반적인 일치를 평가하는 Fleiss카파값은 0.445였다. 결론: 세 임상기관 사이의 경동맥 내막-중막 두께의 측정자간 신뢰도는 훌륭하였으며, 경화반 존재유무에 대한 신뢰도는 적정하였다.

• 생명과학회지
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• 제31권11호
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• pp.1028-1036
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• 2021

반딧불이 루시퍼레이즈(FLuc)는 유전자나 바이러스 치료제에 있어서 효과적인 표적으로 이용될 수 있다. 하지만, 외래 물질이라는 것과 acyl-CoA와의 유사성으로 인하여 FLuc의 임상적 적용은 아직까지 이뤄지지 않았다. 본 연구에서, 우리는 FLuc의 안전성을 보여주기 위한 목적으로 일련의 전임상 실험과 인체실험을 수행했다. 우선, FLuc의 세포막 투과성을 점검하기 위해 FLuc 유전자를 담지한 OTS-412와 FLuc 재조합 단백질을 이용했다. OTS-412를 다양한 세포에 감염시켰을 때, FLuc의 활성은 세포 용해물에서만 관찰됐고, 세포를 배양한 배지에서는 관찰되지 않았다. 재조합 단백질 역시 세포막을 투과하지 못했다. 동물실험에서도 이와 유사한 결과가 관찰됐다. VX-2 종양세포에 처리된 토끼에 OTS-412를 처리했을 때, FLuc의 활성은 오직 종양조직에서만 발견됐고, 다른 장기나 혈액에서는 관찰되지 않았다. FLuc의 인체 반응성을 조사하기 위해 각기 다른 장기에서 유래된 세포 용해물을 FLuc에 반응시켰으나 아무런 활성이 관찰되지 않았다. 마지막으로, FLuc 재조합 단백질을 인체에 정맥주사 방식으로 투여했다. FLuc는 혈액에서 20에서 30분의 반감기를 가지고 분해됐으며, 주사한지 1시간 30분 후에는 검출되지 않았다. 또한, 혈장 샘플이 지방산과 반응을 보이지 않았다. FLuc의 접종 전과 후의 결과를 비교했을 때에도 임상적으로 유의미한 변화가 없었다. 따라서, 본 연구는 FLuc의 안전성에 대한 우려를 종합적으로 불식시킨다.