• Korean Chemical Engineering Research
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• 제57권3호
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• pp.305-312
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• 2019

산화질소(NO)가 혈관 확장, 혈소판 응집 억제, 면역 반응 조절, 상처 치료, 항암 등의 주요 병리 생리학적 프로세스에 관여한다는 사실이 밝혀지면서 최근 산화질소 전달에 대한 국내외 연구진들의 관심이 높아지고 있다. 그러나 인체에 이상적으로 적용될 수 있는 산화질소 전달체의 개발은 산화질소의 높은 반응성과 짧은 반감기로 인하여 여전히 난제로 남아 있다. 본 논문에서는 다양한 산화질소 전달체 중에서도 최근 바이오메디컬 분야에서 연구가 활발히 이루어지고 있는 나노 구조체를 이용한 전달체의 연구 결과 및 응용 방향에 대해서 소개하고자 한다. 나노 크기의 구조체가 다른 전달체와 비교하여 가지는 장점은 표면 대 부피 비율이 높아 산화질소를 효율적으로 탑재할 수 있고, 표면 개조능력이 뛰어나 산화질소의 방출 양상을 효과적으로 제어할 수 있다는 것이다. 특히 이 글에서는 다양한 나노 구조체 중에서도 나노입자 형태, 마이크로에멀젼 형태, 그리고 다층필름 형태의 나노 구조체에 대해서 다룸으로써 각 구조체의 산화질소 방출 양상을 비교하고 그 특징에 대해서 자세히 알아보고자 한다. 이와 같은 나노 구조체의 개발은 산화질소의 급격한 방출을 방지하고 지효성을 띠게 함으로써 타겟 부위에서의 효과를 높일 수 있을 것으로 기대되며, 더 나아가 차후 다양한 바이오메디컬 분야에서 유망한 치료 기제로서 적용될 수 있을 것으로 보인다.

• Design & Manufacturing
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• 제15권2호
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• pp.11-16
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• 2021

Recently, three-dimensional (3D) cell culture systems, which are superior to conventional two-dimensional (2D) vascular systems that mimic the in vivo environment, are being actively studied to reproduce drug responses and cell differentiation in organisms. Conventional two-dimensional cell culture methods (scaffold-based and non-scaffold-based) have a limited cell growth rate because the culture cannot supply the culture medium as consistently as microvessels. To solve this problem, we would like to propose a 3D culture system with an environment similar to living cells by continuously supplying the culture medium to the bottom of the 3D cell support. The 3D culture system is a structure in which microvascular structures are combined under a scaffold (agar, collagen, etc.) where cells can settle and grow. First, we have manufactured molds for the formation of four types of microvessel-mimicking chips: width / height ①100 ㎛ / 100 ㎛, ②100 ㎛ / 50 ㎛, ③ 150 ㎛ / 100 ㎛, and ④ 200 ㎛ / 100 ㎛. By injection molding, four types of microfluidic chips were made with GPPS (general purpose polystyrene), and a 100㎛-thick PDMS (polydimethylsiloxane) film was attached to the top of each microfluidic chip. As a result of observing the flow of the culture medium in the microchannel, it was confirmed that when the aspect ratio (height/width) of the microchannel is 1.5 or more, the fluid flows from the inlet to the outlet without a backflow phenomenon. In addition, the culture efficiency experiments of colorectal cancer cells (SW490) were performed in a 3D culture system in which PDMS films with different pore diameters (1/25/45 ㎛) were combined on a microfluidic chip. As a result, it was found that the cell growth rate increased up to 1.3 times and the cell death rate decreased by 71% as a result of the 3D culture system having a hole membrane with a diameter of 10 ㎛ or more compared to the conventional commercial. Based on the results of this study, it is possible to expand and build various 3D cell culture systems that can maximize cell culture efficiency by cell type by adjusting the shape of the microchannel, the size of the film hole, and the flow rate of the inlet.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.166-174
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• 2021

Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

• 생명과학회지
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• 제31권12호
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• pp.1120-1127
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• 2021

우울증은 높은 유병률과 자살률 증가로 인해 사회적 기능에 부정적인 영향을 미치며, 경제적 부담 또한 높은 질환이다. 우울증은 신경염증, 시냅스 기능장애, 인지 결손과 같은 뇌에서 다양한 현상과 관련이 있다. 임상에서 사용되는 항우울제들은 치료효과가 낮아 빠른 효능을 보이는 항우울제 개발이 시급하다. 현재까지 우울증과 관련된 다양한 유전자, 단백질, 그리고 신호전달계에 대한 많은 연구가 수행되었지만, 우울증의 발생기전은 명확하게 밝혀지지 않았다. Sirtuin 1은 nicotinamide-adenine dinucleotid- (NAD⁺-) dependent histone deacetylases로써 세포 분화, 세포 사멸, 발생, 자가소화작용, 암 대사에 관여하는 것으로 알려져 있다. 최근의 유전연구들은 Sirtuin 1이 우울증의 잠재적 타겟 유전자라고 제안하고 있다. 또한 전임상 연구에서는 Sirtuin 1의 신호전달기전이 우울행동에 영향을 미친다고 보고 하였다. 본 종설에서는 우울증과 Sirtuin 1에 대한 최신 지식을 제시하였다. 소교세포의 활성, 일주기 생체 리듬, 신경세포 생성, 및 인지기능의 조절에 관여하는 Sirtuin 1이 우울증에 미치는 다양한 영향을 설명하였다. 아울러 Sirtuin 1이 우울증 핵심 기전중의 하나인 신경가소성의 손상에 미치는 영향과 그 기전에 대해서 논의하였다.

• 대한본초학회지
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• 제33권1호
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• pp.37-46
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• 2018

Objectives : Liver disease is an inflammatory reaction caused by oxidative stress, viral, alcohol, and drug properties. Inflammatory reaction causes hepatitis and chronic hepatitis is persistent, it progresses to liver fibrogenesis and liver cancer. The aim of this study was to confirm the hepatoprotective effect of Tongyuhwalhyeol-tang(Tongqiaohuoxue Decoction) (TH) and Gamtongyuhawlhyeol-tang(GTH) in TAA-induced liver injury animal model. Methods : The antioxidant activities were evaluated through in vitro experiments, such as 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, total polyphenol and total flavonoid content measurement. To confirm the liver protective effect, induced by Thioacetamide (TAA) for 3 days injection at 200 mg/kg rats. TH and GTH were treated 3 days at 200 mg/kg/day. The changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$), alanine aminotransferanse (ALT) and aspartate aminotransferase (AST) in serum were analyzed after experiment. Also, expression of anti-inflammation, anti-oxidant related proteins were investigated by western blot analysis. Results : TH was inhibited the antioxidant activities. In the TAA-induced rat, TH decreased ROS, $ONOO^-$, ALT, AST level in serum. Inflammation related protein expressions increased in TAA-induced rat compared to normal rat. However, TH group inhibited the down expression of these proteins. Also, anti-oxidant related protein expressions increased in TH group compared TAA-induced rat. Conclusion : Therefor, these results suggested that TH provided hepatoprotective effects on the hepatic injury leading to the reduction of inflammatory response. In addition, the effect of TH was superior to that of GTH.

• Parasites, Hosts and Diseases
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• 제60권1호
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• pp.39-43
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• 2022

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

• Journal of Nutrition and Health
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• 제55권4호
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• pp.430-440
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• 2022

셀레늄은 산화스트레스 방어 기능으로 인체의 면역기능 유지에 필수적 역할을 하고, 세포의 항산화기능, 면역기능, 갑상선호르몬 조절, 약물이나 중금속 위해에 대한 방어, 만성질환의 위험 감소에 필수 역할을 하는 미량무기질이다. 셀레늄 섭취의 부족은 암, 심혈관질환, 당뇨병, 신경질환, 골관절 및 근육괴사와 약화, 갑상선질환, 염증성 질환 등 다양한 만성적 질환의 위험을 높인다. 본 논문은 2020 한국인 영양소 섭취기준에서 셀레늄의 제정과 개정 근거 기준에 대해 설명하고, 셀레늄 데이터베이스의 현황과 향후 2025 한국인 영양소 섭취기준 설정을 위한 필요 연구에 대해 논의하였다. 셀레늄의 2020 한국인 영양소 섭취기준은 2015년에 이어 혈장 셀레노프로테인 P 수준이 최대가 되는 셀레늄의 평균필요량을 지표로 사용하였고, 중국인 대상의 보고치에 한국인의 기준체중과 변이계수를 적용하는 방법이 적용되었으며, 2015년에 비해 참고체중치의 변경에 따라 성별, 연령별 셀레늄 섭취기준에서 약간의 개정이 있었다. 향후 셀레늄 섭취기준 설정의 발전을 위해서는 1) 한국인 대상의 혈장 셀레노프로테인 P의 최대수준을 나타내는 셀레늄 섭취량을 파악하기 위한 셀레늄 중재연구가 필요하고, 2) 셀레늄 섭취량 판정의 정확성을 높이기 위한 영양평가 프로그램내 식품 셀레늄 데이터베이스의 검토와 식품의 셀레늄 함량 분석을 확대해야 하며, 3) 국민의 셀레늄 섭취와 체내 생물학적 지표와의 관계를 건강한 일반인뿐만 아니라 질환자 및 운동선수와 같은 특수 환경의 대상자들로 확대하는 연구가 요구된다.

• Pediatric Infection and Vaccine
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• 제30권1호
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• pp.47-54
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• 2023

최근 광범위 항생제 사용의 증가로 인한 다제내성 그람 음성균의 출현이 전 세계적으로 문제가 되고 있다. 특히 다제내성 녹농균(multidrug-resistant Pseudomonas aeruginosa) 감염의 치료는 어려우며 중환자의 사망률을 증가시키는 원인이 된다. 세프톨로잔-타조박탐(ceftolozane-tazobactam, Zerbaxa^TM)은 5세대 세팔로스포린과 베타락탐 분해효소저해제로 다제내성 녹농균에 의한 복잡성 요로감염과 복잡성 복강내 감염의 치료에 효과가 있는 것으로 입증되었다. 본지에서 저자들은 소아청소년 혈액암 환자에서 발생한 다제내성 녹농균에 의한 균혈증을 세프톨로잔-타조박탐을 사용하여 성공적으로 치료한 국내 첫 번째 사례를 보고하고자 한다.

• Korean Journal of Acupuncture
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• 제40권4호
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• pp.156-168
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• 2023

Objectives : This study aimed to determine the status of thermal stimulation devices approved in Korea for medical applications over the past 10 years, and based on this, to obtain insight for future thermal treatment in Korean medical institutions. Methods : We searched the item classification list entitled "Regulations on Medical Device Items and Rating by Item" from the Ministry of Food and Drug Safety Notice No. 2021-24, 2021 (Enforced March 19, 2021; www.mfds.go.kr) for individually licensed heaters using the terms "heat" and "heating". Results : We identified 17 items of thermal stimulation product group, of which 1,308 devices were licensed by February 4, 2022, and 53.2% of them (n=696) were devices with valid permits for distribution in Korea. Among the licensed devices, heating pad systems under/overlay (electric, home use) were approved the most, but combinational stimulator (for medical use, home use; Grade 2) accounted for the highest percentage among the current valid permission. Moxibustion apparatuses were licensed separately for electrical use and non-electrical use, and occupied a low percentage of the total devices. We analyzed 307 devices that were accompanied by technical documents and found that the heat sources were wires in 145 (47.2%), infrared rays in 44 (14.3%) and ultrasonic waves in 42 (13.7%) devices. Most (83.1%) devices were used for pain relief, while other applications included beauty, cancer treatment, maintenance of infant body temperature, and healing fractures. Conclusions : Thermal stimulation devices accounted for about 0.9% of all medical devices, and among them, combinational stimulators and heating pad systems under/overlay had the most valid permits. Thermal stimulation devices using heating wires and infrared rays were the most prevalent, and most were used to relieve pain. In order to develop a range of thermal stimulation devices that can be utilized in Korean medical institutions, it is imperative that they have potential applications beyond pain management, addressing various medical purposes. To achieve this, foundational research is necessary to effectively apply diverse heat sources based on medical objectives.

• 한국환경보건학회지
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• 제49권6호
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• pp.289-294
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• 2023

Background: Artificial sweeteners are chemically synthesized substances used to add sweetness to foods. Representative substances include aspartame and acesulfame-K, which are 200 times sweeter than sugar. Recently, the IARC classified aspartame as class 2B, but Ministry of Food and Drug Safety of South Korea announced that it would maintain the current usage standards. Acesulfame-K, which has the potential to cause cancer, was excluded from the list of possible carcinogens, raising questions about its safety. According to a survey by the Consumers Union of Korea, 85% of makgeolli includes artificial sweeteners, but the content labelling is not indicated. It is necessary to accurately determine the intake of artificial sweeteners through makgeolli. Objectives: This study aims to evaluate the safety of makgeolli consumption by identifying the content of artificial sweeteners (aspartame, acesulfam-K) and preservatives (sorbic acid). Methods: Twenty makgeolli samples were purchased from large supermarkets and convenience stores by referring to the sales ranking of makgeolli products distributed in South Korea and the purchase ranking from online sites. The sample was sonicated to remove alcohol and carbon dioxide. Nine mL of acetonitrile was mixed with 1 mL of the prepared sample, centrifuged, and the supernatant was filtered and analyzed using HPLC. Results: As a result of the analysis, aspartame was detected in 17 products and acesulfame-K was detected in ten. The ADI of aspartame (40 mg/kg·bw/day) is higher than the EDI based on the maximum concentration 126.5 ㎍/mL. The ADI of acesulfame-K (15 mg/kg·bw/day) is higher than the EDI based on the highest concentration of 82.96 ㎍/mL. Although the health risk is low, IARC has raised the possibility of aspartame causing carcinogenesis, so there is a need to reevaluate the standards and regulations for artificial sweeteners. Conclusions: Through this study, we aimed to determine the content of aspartame and acesulfame-K contained in makgeolli currently distributed in South Korea and the safety of exposure to the human body when consumed.