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포랄루맙 항체와 자성나노입자 접합 구조체의 유체 내 이동속도 특성
최상헌,최종구,하지원,전다인,최유경,이보람,이현숙,이상석,강미경,김은재,강하성,Hasan Mahbub 한국물리학회 2021 새물리 Vol.71 No.11
This study is based on the development of a therapeutic agent using anti-CD3 foralumab monoclonal antibodies which inhibit the overactivation of the T-cells that cause a cytokine storm in the human body. A 7-step process and SiteClick antibody labeling kit was used to bind foralumab antibodies to magnetic nanoparticles through Fc-directed conjugation. The resulting magnetic nanoparticle and antibody composite was compared and analyzed using scanning microscopy, tunneling microscopy, and energy-dispersive spectroscopy. The root-mean-square value of the drift velocity due to Brownian motion of the magnetic nanoparticles (with antibodies attached) in physiological saline, as measured with a nanoparticle tracking analyzer, was 6.98 pix/frame; double that of magnetic nanoparticles without antibodies attached. This was again observed in an animal study when magnetic nanoparticles conjugated to antibodies were injected into the blood vessels of rabbit ears. The antibodies, having a biocompatible functional group attached to their surfaces, showed improved fluidity in bodily fluids. 본 연구는 코로나 바이러스 가 우리 몸에 사이토카인 폭풍을 일으키는 T 세포의 사이토카인 분비증후군을항-CD3 포랄루맙 단클론항체를 사용해서 억제하는 치료제 개발에 기반을 두고 수행하였다. 포랄루맙항체와 자성나노입자들 간의 결합은 7단계 과정들을 포함시킨 SiteClick 항체 라벨링 키트를 사용하여Fc-지향적 접합체를 제작하였다. 접합체는 전자현미경 혹은 투과전자현미경 이미지와 에너지분산스펙트럼으로 비교 분석하였다. 나노입자 추적분석기로 측정한 생리식염수 안에 담긴 항체가 붙은자성나노입자들의 브라운 운동으로 인한 이동속도의 실효값은 항체가 없는 자성나노입자들보다 2배로증가한 6.98 pix/frame 이었다. 이것은 입자의 표면에 부착된 생체적합성 작용기를 갖는 항체가 유체 내에서 더 향상된 유동성을 갖는다는 것을 동물실험으로 토끼 귀의 혈관에 주입시 혈관 순환에서도 확인하였다.
유방암세포에서 세포외 소포체 분비 감소를 통한 glabridin의 항암효과
최상헌,황진헌,백문창,조영은 한국영양학회 2022 Journal of Nutrition and Health Vol.55 No.2
Purpose: Glabridin (GD) is a bio-available isoflavane isolated from the root extract of licorice (Glycyrrhiza glabra L.). It exhibits a variety of pharmacological activities such as antiinflammatory and anti-oxidant activities. However, extracellular vesicles (EVs) secretion and the anti-cancer mechanism of action remains largely unknown. The present study investigates the anticancer effects of GD by determining the inhibition of EVs secretion in the human breast cancer cell line, MDA-MB-231. Methods: Cell viability, reactive oxygen species (ROS) production, migration, invasion rate, and vascular endothelial growth factor (VEGF) concentration were assessed in MDA-MB-231 cells treated with increasing concentrations of GD (0.1, 1, 5, 10, 20 μM). Subsequently, EV secretion and exosomal DEL-1 protein expression were evaluated to determine the anticancer effects of GD. Results: The results showed that GD significantly inhibited the cell proliferation of MDAMB-231 cells in a dose- or time-dependent manner. Also, ROS production and apoptosis marker protein cleaved caspase-3 were significantly increased in GD-treated MDA-MB-231, compared to control. Furthermore, GD exposure resulted in significantly decreased not only migration and invasion rates but also the VEGF concentration, thereby contributing to a reduction in angiogenesis. Interestingly, the concentration and number of EVs as well as EV marker proteins, such as CD63 and TSG101, were decreased in GD-treated MDA-MB-231 cells. Markedly, extracellular matrix protein DEL-1 as angiogenesis factor was decreased in EVs from GD-treated MDA-MB-231 cells. Conclusion: This study identifies that the anti-cancer molecular mechanism of GD is exerted via inhibition of angiogenesis and EVs secretion, indicating the potential of GD as a chemotherapeutic agent for breast cancer.
최상헌,최종구,이상석 사단법인약침학회 2022 Journal of Acupuncture & Meridian Studies Vol.15 No.1
Background: The primo vascular system can be viewed as a circulatory system that plays a therapeutic function in regenerating the body tissue. The anti-CD3 monoclonal antibody was used as an immunotherapeutic agent to treat the novel coronavirus infection (COVID-19). Objectives: In this study, we observed the effect of injecting lymph nodes with Foralumab, an anti- human CD3 epsilon therapeutic monoclonal antibody, on primo vessels. Methods: The structure and atomic stoichiometry of the antibody were determined by transmission electron microscopy and energy dispersive spectroscopy. Alcian blue dying solution was injected into the lymph nodes of the abdominal vena cava of rabbits, and the solution further flowed into the lymph vessels. Results: A primo vessel with primo nodes stained with Alcian blue was clearly visible in the lymph vessel. By injecting Foralumab into lymph nodes of rabbits with lipopolysaccharide-induced inflammation, the floating primo vessel in the lymph vessel appeared thicker and was distinctly visible. Conclusion: The observation of the primo vessel post-treated with Foralumab in the inflamed lymphatic system suggests the possibility of a functional role of the primo vascular circulatory system in pathophysiological conditions.