• 한국진공학회:학술대회논문집
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• 한국진공학회 2016년도 제50회 동계 정기학술대회 초록집
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• pp.372.1-372.1
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• 2016

Recently, there are a lot of diseases all around the world. Out of them, Atherosclerosis (AS) is the most common cause of stroke, cardiovascular mortality, and myocardial infarction. The macrophage-derived foam cell, which is formed by oxidized low-density lipoprotein (oxLDL), is the crucial marker for AS. In this study, we report a label-free capacitance imaging technique with multi-electrode array (MEA). The lipid-rich aorta arch lesions, which are derived from an apolipoprotein-E receptor-deficient (apoE-/-) mouse, exhibit higher capacitance than the lipid-free aorta arch, allowing the capacitance imaging of lipid region in atherosclerosis. To improve the contacts between MEA and tissue, polypyrrole(PPy)-coated multi walled carbon nanotubes (MWNTs) multi electrode array (PPy-MWNTs-MEA) was fabricated. Compared to TiN-MEA, PPy-MWNTs-MEA yielded lower contact impedance and better capacitance images. In addition, we have also developed a flexible MEA using single walled carbon nanotubes on a PET substrate. The lipid region could be discriminated in the capacitance images of the lipid-rich aorta arch lesions measured using flexible MEA, demonstrating a feasibility of in vivo applications.

• Journal of Pharmaceutical Investigation
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• 제40권6호
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• pp.321-332
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• 2010

Growing interest in the nasal route as a drug delivery system calls for a reliable in vitro model which is crucial for efficiently evaluating drug transport through the nasal cells. Various in vitro cell culture systems has thus been developed to displace the ex vivo excised nasal tissue and in vivo animal models. Due to species difference, results from animal studies are not sufficient for estimating the drug absorption kinetics in humans. However, the difficulty in obtaining reliable human tissue source limits the use of primary culture of human nasal epithelial cells. This shortage of human nasal tissue has therefore prompted studies on the "passage" culture of nasal epithelial cells. A serially passaged primary human nasal epithelial cell monolayer system developed by the air-liquid interface (ALI) culture is known to promote the differentiation of cilia and mucin gene and maintain high TEER values. Recent studies on the in vitro nasal cell culture systems for drug transport studies are reviewed in this article.

• The Korean Journal of Physiology and Pharmacology
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• 제19권4호
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• pp.327-334
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• 2015

The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin- A-induced angiogenesis in vivo and ex vivo. Orexin-A-stimulated endothelial tube formation and chemotactic activity were also blocked in SnPP-treated vascular endothelial cells. Orexin-A treatment increased the expression of nuclear factor erythroid-derived 2 related factor 2 (Nrf2), and antioxidant response element (ARE) luciferase activity, leading to induction of HO-1. Collectively, these findings indicate that HO-1 plays a role as an important mediator of orexin-A-induced angiogenesis, and provide new possibilities for therapeutic approaches in pathophysiological conditions associated with angiogenesis.

• 한국식품과학회지
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• 제51권4호
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• pp.398-403
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• 2019

Dioscorea japonica Thunberg (DJ) has been widely used as a healthy food in Korea for the enhancement of physical stamina. Hence, the present study evaluated the immune-enhancing effect of DJ in forced swim test of mouse model. The immobility time of the group treated with DJ for 7 days was significantly reduced in comparison with that of the control group. After a forced swimming test, the changes in blood biochemical parameters and splenic T lymphocyte populations induced by the administration of DJ were assessed. Serum levels of lactic dehydrogenase, creatine phosphokinase, and aspartate aminotransferase were significantly decreased in DJ-administered group compared to the control group. However, administration of DJ did not affect the splenic T lymphocyte populations. Moreover, DJ significantly increased the production of interferon-g and interleukin-2 compared to the media control in splenocytes. Collectively, it may be concluded that DJ is useful for enhancement of physical and immune function.

• Journal of Audiology & Otology
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• 제25권4호
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• pp.217-223
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• 2021

Background and Objectives: In cochlear implant (CI) surgery, the results and causes of revision and reimplantation may guide surgeons in establishing surgical protocols for revision surgery with safe audiological outcomes. The aim of this study was to review our experience in terms of etiology, surgical strategy, and hearing outcomes in pediatric patients who underwent CI removal and reimplantation. Subjects and Methods: All patients received implants of the same brand. Pre and postoperative Categories of Auditory Performance score and aided free-field pure tone audiometry thresholds were noted. In vivo integrity tests were performed for each patient and the results of ex vivo tests of each implant were obtained from manufacturer. Results: A total of 149 CIs were placed in 121 patients aged <18 years. The revision rate in children was 6.7% (10/121 children). Six patients had a history of head injury leading to a hard failure. The causes of reimplantation in others were soft failure (n=1), electrode migration (n=1), infection (n=1), and other (n=1). All patients showed better or similar postreimplantation audiological performance compared with pre-reimplantation results. Conclusions: It is very important to provide a safe school and home environment and educate the family for reducing reimplantation due to trauma. Especially for active children, psychiatric consultation should be continued postoperatively.

• 대한청각학회지
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• 제25권4호
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• pp.217-223
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• 2021

Background and Objectives: In cochlear implant (CI) surgery, the results and causes of revision and reimplantation may guide surgeons in establishing surgical protocols for revision surgery with safe audiological outcomes. The aim of this study was to review our experience in terms of etiology, surgical strategy, and hearing outcomes in pediatric patients who underwent CI removal and reimplantation. Subjects and Methods: All patients received implants of the same brand. Pre and postoperative Categories of Auditory Performance score and aided free-field pure tone audiometry thresholds were noted. In vivo integrity tests were performed for each patient and the results of ex vivo tests of each implant were obtained from manufacturer. Results: A total of 149 CIs were placed in 121 patients aged <18 years. The revision rate in children was 6.7% (10/121 children). Six patients had a history of head injury leading to a hard failure. The causes of reimplantation in others were soft failure (n=1), electrode migration (n=1), infection (n=1), and other (n=1). All patients showed better or similar postreimplantation audiological performance compared with pre-reimplantation results. Conclusions: It is very important to provide a safe school and home environment and educate the family for reducing reimplantation due to trauma. Especially for active children, psychiatric consultation should be continued postoperatively.

• Journal of Chest Surgery
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• 제35권3호
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• pp.171-176
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• 2002

배경: 혈액이 이물질과 접촉을 하면 체내에서 응고 및 염증기전을 활성화 시키게 되고 임상적으로 폐 및 신장 기능의 저하, 출혈 등을 유발할 수 있고 심한 경우 다발성 장기기능 저하까지 발생할 수 있다. 이 때문에 혈액-이물질 접촉표면을 개선하는 여러 가지 시도들이 이루어지고 있고 혈액접촉표면의 적합성을 평가하는 지표의 선택은 대단히 중요하다. 접촉면의 응고기전에서 혈소판의 침착이 가장 중요한 단계이고 혈소판의 침착을 확인하기 위하여 표면흡착 정도를 비교하는 방법이 흔히 사용되고 있는데, 대부분 in-vitro 혹은ex-vivo조건에서 시행되고 있으므로 생체 내 in-vivo상황을 정확히 대변한다고 보기 힘들다. 따라서 본 연구는 in-vivo 실험조건에서 동위원소(radioisotope)를 이용하여 혈소판의 표면흡착 정도를 정량 분석하는 방법의 유용성을 분석하고자 계획되었다. 대상 및 방법: 돼지(20-25 kg, n=6)를 이용하여 하행대동맥 우회회로를 구성하였다. 우회회로는 헤파린 표면처리가 안된 일반 PVC 도관(대조군; Capiox, Terumo, Japan)과 이온결합 헤파린 표면 처리된 PVC 도관(실험군; Duraflo ll, Baxter, USA)을 Y-connector로 연결하여 2개의 회로를 동시에 구성하였다. 수술 전날 동종의 실험동물로부터 혈액을 채취하여 원심분리를 통해 고농도 혈소판 용액(platelet concentrate)을 추출하였고, 수술 당일 동위원소(Tc-99m-HMPAO, 180 $\mu$Ci)을 섞어 30분간 방치한 다음, 10분간 원심분리하여 침전층의 labeling efficiency를 측정하였다. 분리된 침전층에 혈장을 섞어(5 ml) 실험동물에 정맥주사한 후, 전신 헤파린 처치 상태에서(1 mg/kg) 하행대동맥을 차단하여 우회도관 쪽으로 2시간 동안 혈액을 순환시키고 분리하였다. 각 도관의 내강을 생리식염수 500 ml로 동시에 세척한 다음, 일정 간격으로10$\times$10 mm 크기의 절편을 5개 채취하였다. 절편을 세분하여 측정튜브에 담아 동위원소 측정기(gamma counter, Cobra II , Packard ,USA)를 이용하여 Tc-99m-HMPAO의 분당 count수를 측정함으로써 혈소판의 흡착정도를 정량분석 비교하였다. 결과: 동위원소 측정기를 이용한 평균 count수는 각각의 실험군과 대조군의 비율을 이용하여 비교하였다. 평균 count수는 대조군에서 537.3 Ci/min였고 실험군에서는 311.1Ci/min로 측정되었으며, 두 군 사이의 비율은 대조군에 비하여 실험군이 1: 0.58로 통계적으로 유의하였다.(p=0.004) 결론: 위결과를 통하여 실험군이 대조군에 비하여 혈소판 표면흡착측면에서 우수하다는 것을 정량적으로 증명할 수 있었다. 저자 등이 사용한 in-vivo 동위원소 측정법으로 혈소판 흡착정도의 생체 내 실험으로 유용하며 의료용 고분자 재료의 혈액적합성 판정의 지표로 제시하고자 한다.

• Journal of Periodontal and Implant Science
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• 제47권5호
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• pp.292-311
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• 2017

Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal $CD4^+CD25^+CD127^{lo-}$ Tregs (127-Tregs) and $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an $NOD/scid/IL-2R{\gamma}^{-/-}$ mouse model of collagen-induced arthritis. Results: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of $CD4^+CD25^+$ Tregs at the articular joints in a mechanistic and orchestrated way. Conclusions: We propose human $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis.

• Journal of Ginseng Research
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• 제31권2호
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• pp.109-116
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• 2007

Korean red ginseng has broad efficacious effects against hypertension, diabetes, nociception, and cancer, and it counteracts weakness. It has been reported that Korean red ginseng is able to normalize blood pressure, improve cholesterol and lower blood glucose levels. We have recently reported that Korean red ginseng extract (KRGE) significantly prevented rat carotid arterial thrombosis in vivo, and inhibited platelet aggregation ex vivo and in vitro in a dose-dependent manner. The purpose of this study was to examine the effects of KRGE on blood circulation in human by measuring ex vivo platelet aggregation, plasma coagulation and serum lipid profiles in healthy volunteers. Subjects were randomly divided into three groups (placebo-group, KRGE-low dose group, KRGE-high dose group). Administration of KRGE to subjects significantly inhibited ADP-induced platelet aggregations both in KRGE-low dose group from $72.79{\pm}20.53$ to $62.00{\pm}23.06%$ (p=0.0009), and in KRGE-high dose group from $75.14{\pm}21.86$ to $64.52{\pm}24.72%$ (p=0.0039), respectively. Administration of KRGE to subjects also significantly inhibited collagen-induced platelet aggregations both in KRGE-low dose group from $85.52{\pm}12.57$ to $79.62{\pm}20.47%$ (p=0.0916), and in KRGE-high dose group from $80.24{\pm}18.11$ to $70.31{\pm}25.93%$ (p=0.0565), respectively. Whereas, KRGE has no significant effects on coagulation system, such as prothrombin time (PT) and activated partial thromboplastin time (APTT), and serum lipid profiles, such as total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride. KRGE also has no significant effects on hematological and serum biochemical profiles. These results suggest that KRGE has a potential to improve blood circulation through antiplatelet activity in human, and KRGE intake may be beneficial for the individuals with high risks of thrombotic and cardiovascular diseases.

• 대한두경부종양학회지
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• 제19권1호
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• pp.25-33
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• 2003

Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per $10^6$ cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.