• The Korean Journal of Physiology and Pharmacology
• /
• 제24권6호
• /
• pp.441-452
• /
• 2020

In vivo animal models are limited in their ability to mimic the extremely complex systems of the human body, and there is increasing disquiet about the ethics of animal research. Many authorities in different geographical areas are considering implementing a ban on animal testing, including testing for cosmetics and pharmaceuticals. Therefore, there is a need for research into systems that can replicate the responses of laboratory animals and simulate environments similar to the human body in a laboratory. An in vitro two-dimensional cell culture model is widely used, because such a system is relatively inexpensive, easy to implement, and can gather considerable amounts of reference data. However, these models lack a real physiological extracellular environment. Recent advances in stem cell biology, tissue engineering, and microfabrication techniques have facilitated the development of various 3D cell culture models. These include multicellular spheroids, organoids, and organs-on-chips, each of which has its own advantages and limitations. Organoids are organ-specific cell clusters created by aggregating cells derived from pluripotent, adult, and cancer stem cells. Patient-derived organoids can be used as models of human disease in a culture dish. Biomimetic organ chips are models that replicate the physiological and mechanical functions of human organs. Many organoids and organ-on-a-chips have been developed for drug screening and testing, so competition for patents between countries is also intensifying. We analyzed the scientific and technological trends underlying these cutting-edge models, which are developed for use as non-animal models for testing safety and efficacy at the nonclinical stages of drug development.

• Journal of Veterinary Science
• /
• 제22권3호
• /
• pp.25.1-25.16
• /
• 2021

Background: Malignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor. Objectives: In this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs). Methods: A hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system. Results: TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells. Conclusions: SCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.

• Journal of Microbiology and Biotechnology
• /
• 제32권5호
• /
• pp.645-656
• /
• 2022

Gossypol, a natural phenolic aldehyde present in cotton plants, was originally used as a means of contraception, but is currently being studied for its anti-proliferative and anti-metastatic effects on various cancers. However, the intracellular mechanism of action regarding the effects of gossypol on pancreatic cancer cells remains unclear. Here, we investigated the anti-cancer effects of gossypol on human pancreatic cancer cells (BxPC-3 and MIA PaCa-2). Cell counting kit-8 assays, annexin V/propidium iodide staining assays, and transmission electron microscopy showed that gossypol induced apoptotic cell death and apoptotic body formation in both cell lines. RNA sequencing analysis also showed that gossypol increased the mRNA levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and activating transcription factor 3 (ATF3) in pancreatic cancer cell lines. In addition, gossypol facilitated the cleavage of caspase-3 via protein kinase RNA-like ER kinase (PERK), CHOP, and Bax/Bcl-2 upregulation in both cells, whereas the upregulation of ATF was limited to BxPC-3 cells. Finally, a three-dimensional culture experiment confirmed the successful suppression of cancer cell spheroids via gossypol treatment. Taken together, our data suggest that gossypol may trigger apoptosis in pancreatic cancer cells via the PERK-CHOP signaling pathway. These findings propose a promising therapeutic approach to pancreatic cancer treatment using gossypol.

• Journal of Microbiology and Biotechnology
• /
• 제33권4호
• /
• pp.449-462
• /
• 2023

Previously, we confirmed that Mychonastes sp. 246 methanolic extract (ME) markedly reduced the viability of BxPC-3 human pancreatic cancer cells. However, the underlying mechanism ME remained unclear. Hence, we attempted to elucidate the anticancer effect of ME on BxPC-3 human pancreatic cancer cells. First, we investigated the components of ME and their cytotoxicity in normal cells. Then, we confirmed the G1 phase arrest mediated growth inhibitory effect of ME using a cell counting assay and cell cycle analysis. Moreover, we found that the migration-inhibitory effect of ME using a Transwell migration assay. Through RNA sequencing, Gene Ontology-based network analysis, and western blotting, we explored the intracellular mechanisms of ME in BxPC-3 cells. ME modulated the intracellular energy metabolism-related pathway by altering the mRNA levels of IGFBP3 and PPARGC1A in BxPC-3 cells and reduced PI3K and mTOR phosphorylation by upregulating IGFBP3 and 4E-BP1 expression. Finally, we verified that ME reduced the growth of three-dimensional (3D) pancreatic cancer spheroids. Our study demonstrates that ME suppresses pancreatic cancer proliferation through the IGFBP3-PI3K-mTOR signaling pathway. This is the first study on the anticancer effect of the ME against pancreatic cancer, suggesting therapeutic possibilities and the underlying mechanism of ME action.

• Biomolecules & Therapeutics
• /
• 제32권1호
• /
• pp.94-103
• /
• 2024

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 ㎍/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells. Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.

• 천문학회보
• /
• 제42권1호
• /
• pp.30.2-31
• /
• 2017

Compact elliptical (cE) galaxies are in a rare class of stellar systems characterized by high stellar densities, small sizes, high velocity dispersion, and high metallicity corresponding to elliptical galaxies. cE galaxies have been observed around massive galaxies, so they could be formed under strong influences of tidal stripping and truncation. However, the recent discovery of isolated cE galaxies requires the need of new formation scenarios. We aim at finding cE galaxies in various environments using SDSS DR12, and studying stellar population of cEs as function of environments. Based on the typical properties of cE galaxies, we selected cE candidates by restricting that low-luminosity Mg > 19.5 mag, small sizes Re < 700 pc, and high velocity dispersions ${\sigma}$ > $60kms^{-1}$. Since effect radii of cE candidates are mostly smaller than the seeing size of SDSS photometry, we calculated the effective radius by fitting a Sersic profile. In addition, we assumed that host galaxies have brightness with Mr < -21 mag, and an environmental parameter is computed as distances between cE galaxies and host-galaxies. We found 112 cE galaxies at z < 0.05, which have high sersic indices (mean value is 5.2) similar to the typical massive elliptical galaxies. Mgb values of cE galaxies increase as the distances from the host galaxies decrease. Especially, for cEs close to the host galaxies (NcE; $D_{host}$ < 300 pc), the Mgb values are similar to those of massive elliptical galaxies, which is consistent with the previous studies. On the other hand, cE galaxies distant from the host galaxies (DcE; Dhost >300 pc) have lower Mgb values than the conventional cE. The Mgb values follow the ${\sigma}$-Mgb relation of elliptical galaxies, and are connected to its faint end. This can be explained as a result of different merger histories for differing environments. For example, NcE galaxies are formed by tidal stripping by massive galaxies as suggested by previous studies, but DcE galaxies could be linked with high-redshift spheroids (e.g. red nuggets) which have not evolved into present-day elliptical galaxies because of the environmental influences.

• 한국광물학회지
• /
• 제21권1호
• /
• pp.27-35
• /
• 2008

천연 광물소재를 양이온 치환하여 환경개선재로 응용되고 있는 $Lumilite^{(R)}$의 원료 중 원광의 광물학적 특징을 분석하고 구성광물의 나노결정의 발달특징을 관찰하였다. 이를 위하여 편광현미경에 의한 조직관찰, XRD, SEM, FTIR, XRF 분석을 실시하였다. 구성 광물상은 클리높틸로라이트, 일라이트, 석영, 알바이트 사장석이며, 본 시료는 미립질의 치밀한 조직을 가지는 것이 특징이다. 나노결정의 크기는 $70{\sim}100\;nm$ 범위가 흔하면, 비교적 등립질 내지 반등립질로 구성된다. 나노결정들의 단면은 아원형 내지 완만한 각형이며, 나노결정의 표면에는 수 nm 크기의 원형돌기가 거의 균질하게 분포한다. 전시료의 화학조성은 $SiO_2$ $74.22{\sim}75.65\;wt.%$, $Al_2O_3$ $13.25{\sim}13.72\;wt.$, CaO $4.23{\sim}5.15\;wt.%$이며, 그 외 주성분과 수분은 미량으로 함유된다. 원료물질은 결정학적으로 $500^{\circ}C$까지는 안정한 상을 유지하나, $700^{\circ}C$에서는 구조가 거의 파괴된다. $Lumilite^{(R)}$가 흡착능력이 뛰어나고 높은 양이온치환능력을 가지는 것은 나노결정들이 잘 발달하고, 이들 사이에는 다양한 미세공극이 잘 발달하기 때문인 것으로 보인다.

• 대한조선학회논문집
• /
• 제33권3호
• /
• pp.35-47
• /
• 1996

포텐셜을 기저로 하는 판요소법을 사용하여 자유 표면이 존재하는 유동장에서 일정 속도로 전진하는 3차원 물체의 형상을 설계하였다. 설계 방법으로는 원하는 압력 분포를 경계 조건으로 부여하고 이를 만족하는 물체 형상을 찾아내는 역해석법(inverse method)을 사용하였다. 즉, 주어진 압력으로부터 물체 표면에 분포된 법선 다이폴의 세기인 포텐셜 값을 결정하게 되며, 이는 물체 표면에 대한 Dirichlet형태의 경계 조건으로서 Green의 정리로부터 유도된 적분 방정식을 해석하게 된다. 전체 속도 포텐셜은 기본 유동인 선속에 대한 성분과 선제에 의하여 교란되는 성분으로 구성되어진다고 가정하였으며, 교란 포텐셜을 사용하여 선형화된 자유 표면 경계 조건을 적용하였다. 적분 방정식에 대한 수치 해석을 위해 물체 표면에 법선 다이폴과 Rankine 쏘오스를 분포하였으며, 자유 표면에는 Rankine 쏘오스를 분포하고 4점 유한 차분법을 사용하여 자유 표면 경계 조건이 만족되도록 하였다. 해로서 얻어지는 각 판요소에서의 Rankine 쏘오스의 세기는 가상의 유동 출입량으로서 형상 수정항으로 사용되었다. 몰수 회전 타원체의 형상 설계에 대하여 본 설계법을 적용한 결과 무한 수심에서나 조파 상태에서 $4{\sim}6$회의 반복 계산으로 충분히 수렴된 해를 얻을 수 있었다. 또한 자유 표면을 가르고 전진하는 Wigley 수학적 선형에 대한 형상 설계를 수행하여 만족스러운 결과를 얻어내었으며, 얻어진 수치해는 매우 안정적이고 빠른 수렴성을 보였다. 선형의 우열 비교를 통해 조파 저항을 감소시킬 수 있는 압력 분포의 형태를 파악하였으며, 이를 바탕으로 조파 저항의 관점에서의 5500TEU급 콘테이너 운반선의 설계를 수행하였다. 설계되어진 새로운 선형은 조파 저항의 관점에서 기존의 선형보다 계산과 실험에서 모두 우수하게 개량된 것으로 나타났다.

• Journal of Microbiology and Biotechnology
• /
• 제31권7호
• /
• pp.933-941
• /
• 2021

Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 ㎍/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway including WNT5A, β-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.

• Journal of Radiation Protection and Research
• /
• 제39권1호
• /
• pp.7-13
• /
• 2014

인광석 취급 산업체에서는 천연방사성물질(NORM)을 함유한 물질을 다량으로 취급하고 있어, 종사자들은 각 공정에서 발생하는 공기 중 입자의 흡입에 의해 내부피폭을 받을 수 있다. 흡입에 의한 내부피폭 방사선량은 입자의 특성에 의해 크게 좌우된다. 따라서 본 연구에서는 국내 최대 인광석 취급 산업체에서 공기 중 부유 입자의 크기 분포 및 농도, 입자의 모양 및 밀도, 그리고 방사능 농도를 평가 하였다. 다단계입자채집기를 이용하여 공기 중 입자를 채집하고 입자의 크기분포, 농도, 그리고 모양을 분석하였다. 입자의 공기역학적 직경은 0.03-100 ${\mu}m$까지 광범위하게 분포하였으며, 입자크기가 4.7-5.8 ${\mu}m$(기하학적 평균직경 = 5.22 ${\mu}m$) 혹은 5.8-9.0 ${\mu}m$(기하학적 평균직경 = 7.22 ${\mu}m$)인 범위에서 공기 중 입자의 농도가 최댓값을 나타냈다. 공기 중 부유입자의 농도는 공정에 따라 최대 수백 배 이상 차이를 보였으며, 중장비 작업이 이루어지는 창고에서 높은 농도를 보였다. 반면에 인산석고 적치장에서는 입자의 부유방지를 위한 덮개 및 살수 그리고 비료공장 제어실에서는 환기시설을 갖추고 있어 상대적으로 입자의 공기 중 농도가 낮게 나타났다. 입자의 모양은 모든 측정 장소에서 구형에 가깝게 나타났으므로, 인광석 취급 시설에서 발생하는 입자의 모양인자 값을 1로 정하였다. 각 공정에서 시료를 채집하여 입자의 밀도를 분석하였다. 인광석의 밀도는 약 3.1-3.4 $gcm^{-3}$, 염화칼륨의 밀도는 약 2.7 $gcm^{-3}$, 공정 부산물인 인산석고의 밀도는 약 2.1-2.6 $gcm^{-3}$, 최종제품인 복합비료의 밀도는 약 1.7 $gcm^{-3}$으로 나타났다. 감마분석기를 이용하여 원료물질, 공정부산물, 생산제품 내 $^{226}Ra$, $^{228}Ra$, $^{40}K$ 핵종의 방사능 농도를 측정하였다. 인광석에는 주로 우라늄계열 핵종을 많이 함유하고 있었으며, 그 농도는 원료 산지에 따라 94-866 $Bqkg^{-1}$ 정도였다. 인광석 내에 존재하는 우라늄계열 핵종 중 우라늄은 생산품인 인산 혹은 비료에 농축되었으며, 라듐은 부산물인 인산석고에 농축되었다. 최종제품인 비료의 경우에는 $^{226}Ra$과 $^{228}Ra$이 거의 존재하지 않았으나, 제품생산을 위해 첨가한 염화칼륨에 의해 $^{40}K$의 방사능 농도가 5,000 $Bqkg^{-1}$로 높게 나타났다. 본 연구에서 생산한 인광석 취급 산업체의 입자의 특성 평가 자료는 인산염 취급 산업체 종사자에 대한 방사선학적 안전성 평가에 이용될 수 있을 것이며, 최근 시행된 생활주변방사선 안전관리법에 따른 생활주변방사선 안전관리의 체계를 수립하기 위한 자료로 활용될 수 있을 것이다.