• Title/Summary/Keyword: spheroids

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Monoterpenoid Loliolide Regulates Hair Follicle Inductivity of Human Dermal Papilla Cells by Activating the AKT/β-Catenin Signaling Pathway

  • Lee, Yu Rim;Bae, Seunghee;Kim, Ji Yea;Lee, Junwoo;Cho, Dae-Hyun;Kim, Hee-Sik;An, In-Sook;An, Sungkwan
    • Journal of Microbiology and Biotechnology
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    • v.29 no.11
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    • pp.1830-1840
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    • 2019
  • Loliolide is one of the most ubiquitous monoterpenoid compounds found in algae, and its potential therapeutic effect on various dermatological conditions via agent-induced biological functions, including anti-oxidative and anti-apoptotic properties, was demonstrated. Here, we investigated the effects of loliolide on hair growth in dermal papilla (DP) cells, the main components regulating hair growth and loss conditions. For this purpose, we used a three-dimensional (3D) DP spheroid model that mimics the in vivo hair follicle system. Biochemical assays showed that low doses of loliolide increased the viability and size of 3D DP spheroids in a dose-dependent manner. This result correlated with increases in expression levels of hair growth-related autocrine factors including VEGF, IGF-1, and KGF. Immunoblotting and luciferase-reporter assays further revealed that loliolide induced AKT phosphorylation, and this effect led to stabilization of β-catenin, which plays a crucial role in the hair-inductive properties of DP cells. Further experiments showed that loliolide increased the expression levels of the DP signature genes, ALP, BMP2, VCAN, and HEY1. Furthermore, conditioned media from loliolide-treated DP spheroids significantly enhanced proliferation and the expression of hair growth regulatory genes in keratinocytes. These results suggested that loliolide could function in the hair growth inductivity of DP cells via the AKT/β-catenin signaling pathway.

Enhancement of anti-inflammatory and anti-tumorigenic properties of 3D-spheroid formed mesenchymal stem cells derived from rheumatoid arthritis joints

  • Seung-Chan Lee;Chae-Yeon Hong;Yong-Ho Choe;Tae-Seok Kim;Won-Jae Lee;Gyu-Jin Rho;Sung-Lim Lee
    • Journal of Animal Reproduction and Biotechnology
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    • v.37 no.4
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    • pp.246-254
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    • 2022
  • Current studies have revealed the capacity of mesenchymal stem cells (MSCs) in term of immunomodulatory properties, and this distinct potential is downgraded according to the disease duration of patients-derived MSCs. In order to enhance the immunomodulatory and anti-tumorigenic properties of the rheumatoid arthritis (RA) joints-derived MSCs, we aggregate synovial fluid-derived MSCs from RA joints (RA-hMSCs) into 3D-spheroids by the use of hanging drop culture method. Cells were isolated from synovial fluids of RA joints with longstanding active status over 13 years. For aggregation of RA-hMSCs into 3D-spheroids, cells were plated in hanging drops in 30 μL of advanced DMEM (ADMEM) containing 25,000-30,000 cells/drop and cultured for 48 h. To analyze the comparative immunomodulatory effects of 3D-spheroid and 2D monolayer cultured RA-hMSCs and then cells were cultured in ADMEM supplemented with 20% of synovial fluids of RA patients for 48 h and were evaluated by qRT-PCR for their expression of mRNA levels of inflammatory and anti-inflammatory markers. Cellular aggregation of RA-hMSCs was observed and cells were aggregate into a single sphere. Following treatment of RA patient's synovial fluids into the RA-hMSCs, spheroids formed RA-hMSCs showed significantly (p < 0.05) higher expression of TNFα stimulated gene/protein 6 (TSG-6) than the monolayer cultured RA-hMSCs. Therefore, the 3D-spheroid culture methods of RA-hMSCs were more effective than 2D monolayer cultures in suppressing inflammatory response treated with 20% of RA-synovial fluids by expression of TNFα (TSG-6) according to the immune response and enhanced secretion of inflammatory factors.

Morphologic Changes in Microcystin-LR Treated Hepatocytes In vitro

  • Rhee, Seong-Hee;Kim, Bum-Seok;Lim, Chae-Woong
    • Toxicological Research
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    • v.22 no.3
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    • pp.301-306
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    • 2006
  • Microcystin-LR(MC-LR), a cyanobacterial toxin produced by Microcystis aeruginosa, causes severe hepatotoxicity. Here we investigated the morphologic changes of rat hepatocyte spheroid induced by exposure of MC-LR($10^{-6}M$) in vitro. In addition, to determine the effects of such toxin in the process of hepatocyte spheroid formation, primarily isolated hepatocytes were incubated with MC-LR and the process of spheroid formation was observed. In both hepatocyte spheroid and suspension culture systems, the morphologic changes caused by MC-LR were noticible at 5 min post exposure and were characterized by the loss of microvilli, cytoplasmic vacuolation, the accumulation of lipid droplets, and blob formation. Especially, the size and numbers of blob on the cell surface were increased as the incubation time prolonged and the appearance of electron dense bodies were observed in the cytoplasm of hepatocyte at 20 min post exposure. Furthermore, bile canaliculi-like structures in the hepatocyte spheroids were slightly widened and the process of spheroids formation was inhibited in the isolated hepatocytes incubated with MC-LR. These results indicate that morphologic changes in. the hepatocyte membrane and organelles seem to be typical events in showing the MC-LR induced hepatotoxic effects and the spheroid culture method might be a useful experimental tool to evaluate hepatoxicity since it reflects the in vivo status of hepatocytes.

Combined Treatment of Sodium Salicylate and Genistein Induces Incomplete Apoptosis and Necrosis in MCF-7 Multicellular Tumor Spheroids (MCF-7 MTS에서 sodium salicylate과 genistein 복합처리는 불완전한 세포사멸과 세포괴사를 유도한다)

  • Lee, Su-Yeon;Kim, Cho-Hee;Jeon, Hyun-Min;Ju, Min-Kyung;Kim, Min-Young;Jeong, Eui-Kyong;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
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    • v.22 no.9
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    • pp.1145-1151
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    • 2012
  • Aspirin and its deacetylated form, sodium salicylate (NaSal), have been shown to exert chemopreventive activities against many human cancers including those of the colon, lung, and breast. Previously, we showed that combined treatment of NaSal and genistein synergistically induced apoptosis in A549 lung cancer cells, indicating that these two natural chemicals could be used in combination for cancer therapy. In this study, we examined effects of NaSal/genistein combined treatment on other cancer cells and in three-dimensional multicellular tumor spheroid (MTS) and in an in vitro solid tumor model. We found that the combined treatment induces apoptosis in the HCT116 cells and the A549 cells, but not in the MCF-7 cells. Interestingly, the MCF-7 cells responded to the NaSal/genistein combined treatment by undergoing cell death when they were cultivated as MTS. The combined treatment induced apoptosis at an earlier stage in the MCF-7 MTS culture. However, when the MCF-7 MTS was cultivated for a longer period, it induced necrosis rather than apoptosis. We further found that the apoptotic pattern observed in MCF-7 MTS was incomplete: the chromatins were condensed and fragmented, but the nuclear membrane was still intact. Taken together, these results demonstrate that the NaSal/genistein combined treatment induces incomplete apoptosis and necrosis in the MCF-7 MTS culture system.

STATIONARY, AXISYMMETRIC BLACK HOLE MAGNETO SPHERES IN OBLATE SPHEROIDAL COORDINATES (축대칭을 만족하고 시간에 따라 변하지 않는 블랙홀 자기권의 편원 좌표계적 기술)

  • PARK SEOK JAE;FLETCHER ANDRE B.
    • Publications of The Korean Astronomical Society
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    • v.16 no.1
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    • pp.11-14
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    • 2001
  • In this paper, we simplify the equations of the Macdonald-Thome black hole magnetosphere. Our major assumption is that the 3-D electric and magnetic flux isosurfaces respectively form families of confocal oblate spheroids and hyperboloids. As a result, the magnetospheric equations are greatly simplified, and may provide a useful framework for instances when rigorous, theoretical approaches are not necessary.

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Analysis on Induced Current Density inside Human Body by 60 Hz ELF Magnetic Fields (60Hz ELF자계에 의한 인체내부 유도 전류밀도 해석)

  • Min Suk Won;Song Ki Hyun
    • Proceedings of the KIEE Conference
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    • summer
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    • pp.581-583
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    • 2004
  • This paper analysed the induced current density characteristics inside human body by extremely low frequency magnetic fields according to varying conductivities of human model. Human model was composed of several organs and other parts of 곳 human body, whose shapes were spheroids or cylinders. Organs taken into account were the brain, heart, lungs, liver and intestines. Applying the boundary element method to the human model, effects of the organ conductivity difference to the induced current distribution were estimated.

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Theory of Capillarity of Laplace and birth of Mathematical physics (라플라스 모세관이론과 수학물리학의 태동)

  • Lee, Ho-Joong
    • Journal for History of Mathematics
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    • v.21 no.3
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    • pp.1-30
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    • 2008
  • The success of Newton's Gravitational Theory has influenced the theory of capillarity, beginning in the early nineteenth century, by providing a major model of molecular attraction. He used the equation of the attraction of spheroids, which is expressed by second order partial differential equations, to utilize this analogy as the same kind of a particle's force, between gravitational, refractive force of light, and capillarity. The solution of the differential equation corresponds to the geometrical figure of the vessel and the contact angle which is made by the fluid. Unknown abstract functions $\varphi(f)$ represent interaction forces between molecules, giving their potential functions. By conducting several kinds of experimental conditions, it was found that the height of the ascending fluid in the tube is inversely proportional to the rayon of the tube or the distance of the plate. This model is an essential element in the theory of capillarity. Laplace has brought Newtonian mechanics to completion, which relates to the standard model of gravitational theory. Laplace-Young's equation of capillarity is applicable to minimal surfaces in mathematics, to surface tensional phenomena in physics, and to soap bubble experiments.

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