• 대한의용생체공학회:의공학회지
• /
• 제41권6호
• /
• pp.228-234
• /
• 2020

Superparamagnetic iron oxide nanoparticles (SPIONs) are approved by the Food and Drug Administration (FDA) in the United States. SPIONs are used in magnetic resonance imaging (MRI) as contrast agents and targeted delivery in nanomedicine using external magnet sources. SPIONs act as an artificial peroxidase (i.e., nanozyme), and these reactions were highly stable in various pH conditions and temperatures. In this study, we report a nanozyme ability of the clustered SPIONs (CSPIONs) synthesized by the oil-in-water (O/W) method and coated with biocompatible poly(lactic-co-glycolic acid) (PLGA). We hypothesize that the CSPIONs can have high sensitivity toward H2O2 derived from the reaction between a fixed amount of glucose and glucose oxidase (GOX). As a result, CSPIONs oxidized a 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) commonly used as a substrate for hydrogen peroxidase in the presence of H2O2, leading to a change in the color of the substrate. We also utilized a colorimetric assay at 417 nm using various glucose concentrations from 5 mM to 1.25 μM to validate β-D-glucose detection. This study demonstrated that the absorbance value increases along with increasing the glucose level. The results were highly repeated at concentrations below 5 mM (all standard deviations < 0.03). Moreover, the sensitivity and limit of detection were 1.50 and 5.44 μM, respectively, in which CSPIONs are more responsive to glucose than SPIONs. In conclusion, this study suggests that CSPIONs have the potential to be used for glucose detection in diabetic patients using a physiological fluid such as ocular, saliva, and urine.

• Biomolecules & Therapeutics
• /
• 제30권5호
• /
• pp.427-434
• /
• 2022

The drug repurposing strategy has been applied to the development of emergency COVID-19 therapeutic medicines. Current drug repurposing approaches have been directed against RNA polymerases and viral proteases. Recently, we found that the inhibition of the interaction between the SARS-CoV-2 structural nucleocapsid (N) and spike (S) proteins decreased viral replication. In this study, drug repurposing candidates were screened by in silico molecular docking simulation with the SARS-CoV-2 structural N protein. In the ChEMBL database, 1994 FDA-approved drugs were selected for the in silico virtual screening against the N terminal domain (NTD) of the SARS-CoV-2 N protein. The tyrosine 109 residue in the NTD of the N protein was used as the center of the ligand binding grid for the docking simulation. In plaque forming assays performed with SARS-CoV-2 infected Vero E6 cells, atovaquone, abiraterone acetate, and digoxin exhibited a tendency to reduce the size of the viral plagues without affecting the plaque numbers. Abiraterone acetate significantly decreased the accumulation of viral particles in the cell culture supernatants in a concentration-dependent manner. In addition, abiraterone acetate significantly decreased the production of N protein and S protein in the SARS-CoV-2-infected Vero E6 cells. In conclusion, abiraterone acetate has therapeutic potential to inhibit the viral replication of SARS-CoV-2.

• 대한방사성의약품학회지
• /
• 제6권2호
• /
• pp.61-68
• /
• 2020

Aggregated neurofibrillary tangles (NFTs) are a pathological hallmark in Alzheimer's disease (AD) and many radiopharmaceuticals targeting NFTs have been developed so far. Among these, [¹⁸F]flortaucipir (TAUVID^TM) is the first approved radiopharmaceutical in the Food and Drug Administration (FDA) to image tau pathology. In the present study, we describe the optimized radiosynthetic method for the routine production of [¹⁸F] flortaucipir using a commercialized automation module (i.e. GE TRACERlab^TM FX_FN pro). [¹⁸F]Flortaucipir was prepared by nucleophilic substitution from its N-tert-butoxycarbonyl protected nitro precursor, tertbutyl 7-(6-nitropyridin-3-yl)-5H-pyrido[4,3-b]indole-5-carboxylate, at 130℃ for 10 min in dimethyl sulfoxide. The mean radiochemical yield was 20 ± 4.3% (decay-corrected, n = 47) with the molar activity of 218 ± 32 GBq/µmol at the end of synthesis. The radiochemical purity was determined to be above 95%. The overall production time including quality control is approximately 100min. The final produced [¹⁸F]flortaucipir injection meets the USP criteria for quality control. Thus, this fully automated system is validated for clinical use.

• Biomolecules & Therapeutics
• /
• 제31권5호
• /
• pp.484-495
• /
• 2023

Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)- β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

• Fisheries and Aquatic Sciences
• /
• 제26권2호
• /
• pp.133-144
• /
• 2023

Auranofin is a US Food and Drug Administration (FDA)-approved anti-arthritis medication that functions as a thioredoxin reductase inhibitor. Spermidine, a polyamine present in marine algae, can exert various physiological functions. Herein, we examined the synergistic anticancer activity of auranofin and spermidine in hepatocellular carcinoma (HCC). Combined treatment with auranofin and spermidine suppressed cell viability more efficiently than either treatment alone in HCC Hep3B cells. The isobologram plotted by calculating the half maximal inhibitory concentration (IC₅₀) values of each drug indicated that the two drugs exhibited a synergistic effect. Based on the analysis of annexin V and cell cycle distribution, auranofin and spermidine markedly induced apoptosis in Hep3B cells. Moreover, auranofin and spermidine increased mitochondria-mediated apoptosis by promoting mitochondrial membrane potential (Δψm) loss. Auranofin and spermidine significantly increased reactive oxygen species (ROS) production in Hep3B cells, and the blocking ROS suppressed apoptosis induced by spermidine and auranofin. In addition, auranofin and spermidine reduced the expression of phosphorylated phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt), and PI3K inhibitor accelerated auranofin- and spermidine-induced apoptosis. Using ROS scavenger and PI3K inhibitor, we revealed that ROS acts upstream of auranofin- and spermidine-induced apoptosis. Collectively, our study suggests that combination treatment with auranofin and spermidine could afford synergistic anticancer activity via ROS overproduction and reduced PI3K/Akt signaling pathway.

• Medical Lasers
• /
• 제8권1호
• /
• pp.19-23
• /
• 2019

Background and Objectives The picosecond 755 nm alexandrite laser was first approved by the US FDA in 2012. A previous study described the use of a 1,064 nm picosecond laser with a micro-lens array (MLA) in peri-areolar scarring from breast reconstruction surgery and reported significant improvement in the texture and aesthetic appearance of the scar without other wound complications. The purpose of this study was to evaluate the improvement of overall scarring, not just pigmentation, in the picosecond laser treatment of patients with pigmentations. Materials and Methods Sixteen patients who underwent 1,064 nm picosecond laser treatment from June 2016 to December 2018 were enrolled in this study. Patients received two to six sessions of picosecond laser treatment at intervals of 4 weeks. Before and after the laser treatment, the patients evaluated their own satisfaction score and a physician evaluated the Vancouver Scar Scale. To evaluate the satisfaction score and complication rate, a retrospective chart review was done. Results Seven were female and nine were male. The mean of the patients' satisfaction score before the treatment was 1.44 (interquartile range [IQR], 1-2) and 3.00 (IQR 2.25-3.75) six months after treatment. The mean of the Vancouver Scar Scale before the treatment was 9.69 (IQR 8-11), and 6.25 (IQR 5-7.75) six months after treatment. All the results were statistically significant (p<0.01). Conclusion This study provides evidence that the use of a 1,064 nm picosecond laser treatment for pigmented scars can be effective in improving the pigmentation and overall scar status, including vascularity, height, and pliability, with the results of a decrease in the VSS scores between treatments.

• Journal of Digestive Cancer Research
• /
• 제5권1호
• /
• pp.66-69
• /
• 2017

대장암의 치료에 여러 약물이 사용되지만, 5-FU는 오랫동안 대장암의 항암치료의 근간이 되고 있다. Capecitabine은 경구 복용하는 5-FU의 전구체로서, 최근 전이성 대장암의 치료에 사용이 증가되고 있는 약물이다. 저자들은 전이성 대장암 환자에서 고식적인 항암화학요법으로 1차 치료로서 FOLFOX에 좋은 반응을 보였으나, 부작용으로 중단 후 2차 치료로서 Capecitabine 단독요법만을 시행하였음에도 지속적으로 좋은 반응을 보이며 추적관찰하고 있는 사례를 문헌고찰과 함께 보고하는 바이다.

• Journal of Digestive Cancer Research
• /
• 제4권2호
• /
• pp.64-76
• /
• 2016

The step-wise process of colorectal carcinogenesis from aberrant crypt foci, adenoma to adenocarcinoma, is relatively suitable for chemopreventive intervention. Accumulated evidences have revealed that maintaining an undifferentiated state (stemness), inflammation, and oxidative stress play important roles in this colon carcinogenesis process. However, appropriate molecular targets that are applicable to chemopreventive intervention regarding those three factors are still unclear. In this review, we summarized appropriate molecular targets by identification and validation of the prospective targets from a comprehensive overview of data that showed colon cancer preventive effects in clinical trials, epidemiological studies and basic research. We first selected a study that used aspirin, statins and metformin from FDA approved drugs, and epigallocatechin-gallate and curcumin from natural compounds as potential chemopreventive agents against colon cancer because these agents are considered to be promising chemopreventive agents. Experimental and observational data revealed that there are common target molecules in these potential chemopreventive agents: T-cell factor/lymphoid enhancer factor (TCF/LEF), nuclear factor-&B (NF-κB) and nuclear factor-erythroid 2-related factor 2(NRF2). Moreover, these targets, TCF/LEF, NF-κB and NRF2, have been also indicated to suppress maintenance of the undifferentiated state, inflammation and oxidative stress, respectively. In the near future, novel promising candidate agents for colon cancer chemoprevention could be identified by integral evaluation of their effects on these three transcriptional activities.

• 접착 및 계면
• /
• 제24권4호
• /
• pp.113-119
• /
• 2023

홍합의 수중 접착능력은 도파(DOPA)와 라이신(Lysine), 히스티딘(Histidine)과 같은 홍합접착단백질의 아미노산 잔기가 중요한 역할을 한다고 보고되었고, 이에 따라, 카테콜과 아민기를 동시에 갖는 접착성 카테콜아민(Catecholamine) 물질을 기반으로 다양한 의공학적 연구가 진행되고 있다. 카테콜기가 도입된 키토산은 아민이 풍부한 키토산에 카테콜기를 도입한 카테콜아민으로, 이를 이용하여 조직접착제나 창상치유제, 지혈제, 약물전달체 및 조직공학용 담체 등 다양한 의공학적 적용이 가능하다. 특히, 키토산-카테콜 물질은 지혈제로 미국 및 한국 식품의약품안전처의 승인을 받아, 연구개발에서부터 제품개발까지 이루어진 홍합 모사 물질이다. 이에 본 총설에서는 지혈제로써의 키토산-카테콜 물질에 대한 연구 동향을 살펴보고자 한다. 이를 위해, 카테콜기가 도입됨에 따라 나타나는 키토산-카테콜의 특성, 지혈 메커니즘, 다양한 제형에 대하여 다루고자 한다.

• Tuberculosis and Respiratory Diseases
• /
• 제57권4호
• /
• pp.358-363
• /
• 2004

연구배경 : 폐암에서 광역동치료는 미세침습성 비소세포폐암 및 기관지폐쇄를 일으키는 악성종양에 대한 기관지내 치료를 미국식품의약국(FDA)에서 승인한 상태이다. 국내에서는 폐암세포주에 대한 보고 외에 폐암에 대한 광역동치료 연구가 많지 않아 임상 성적에 대한 보고가 없어 이에 저자들은 폐암에서 시행된 광역동치료에 대한 결과를 문헌고찰과 함께 보고하고자 한다. 방 법 : 2002년 8월부터 2003년 5월까지 조선대학교 병원에서 기관지 내시경을 통해 조직학적으로 진단된 폐암환자 중 10명을 대상으로 하여 광역동치료 48시간 전에 광과민제(Photogem$^{(R)}$, Lomonosov institute of Fine Chemical, Russia)를 2.0mg/Kg을 정맥 주사한 후 48시간, 72시간에 Diode LASER system(Biolitec Inc., Germany, wavelength; 633nm)을 사용하여 광역 동치료를 시행하였다. 결 과 : 10명 중 9예에서 부분관해와 함께 기관지 개통을 보였으며, 1예에서는 변화를 보이지 않았다. 결 론 : 저자들은 광역동치료를 통해 기관지폐쇄로 인한 호흡곤란 및 기관지 폐쇄와 관련된 폐렴이 개선됨을 확인 하였으며, 합병증이 적어 안전한 기관지내 치료법으로 생각된다. 앞으로 광역동 치료에 대한 장기적인 결과 및 적절한 치료 적응증 및 조기 폐암에서 치료효과 등에 대한 연구가 필요할 것으로 생각된다.