• Title/Summary/Keyword: Bioactivity

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Modulation of Human Cardiac Progenitors via Hypoxia-ERK Circuit Improves their Functional Bioactivities

  • Jung, Seok Yun;Choi, Sung Hyun;Yoo, So Young;Baek, Sang Hong;Kwon, Sang Mo
    • Biomolecules & Therapeutics
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    • v.21 no.3
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    • pp.196-203
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    • 2013
  • Recent accumulating studies have reported that hypoxic preconditioning during ex vivo expansion enhanced the self-renewal or differentiation of various stem cells and provide an important strategy for the adequate modulation of oxygen in culture conditions, which might increase the functional bioactivity of these cells for cardiac regeneration. In this study, we proposed a novel priming protocol to increase the functional bioactivity of cardiac progenitor cells (CPCs) for the treatment of cardiac regeneration. Firstly, patient-derived c-$kit^+$ CPCs isolated from the atrium of human hearts by enzymatic digestion and secondly, pivotal target molecules identified their differentiation into specific cell lineages. We observed that hCPCs, in response to hypoxia, strongly activated ERK phosphorylation in ex vivo culture conditioning. Interestingly, pre-treatment with an ERK inhibitor, U0126, significantly enhanced cellular proliferation and tubular formation capacities of CPCs. Furthermore, we observed that hCPCs efficiently maintained the expression of the c-kit, a typical stem cell marker of CPCs, under both hypoxic conditioning and ERK inhibition. We also show that hCPCs, after preconditioning of both hypoxic and ERK inhibition, are capable of differentiating into smooth muscle cells (SMCs) and cardiomyocytes (CMs), but not endothelial cells (ECs), as demonstrated by the strong expression of ${\alpha}$-SMA, Nkx2.5, and cTnT, respectively. From our results, we conclude that the functional bioactivity of patient-derived hCPCs and their ability to differentiate into SMCs and CMs can be efficiently increased under specifically defined culture conditions such as short-term hypoxic preconditioning and ERK inhibition.

Fabrication of Porous 3-Dimensional Ti Scaffold and Its Bioactivity by Alkali Treatment (다공성 3차원 Ti 지지체의 제조 및 알카리처리에 따른 생체활성 평가)

  • An, Sang-Hyun;Kim, Seung-Eon;Kim, Kyo-Han;Yun, Hui-Suk;Hyun, Yong-Taek
    • Korean Journal of Materials Research
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    • v.19 no.7
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    • pp.362-368
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    • 2009
  • Ti scaffolds with a three-dimensional porous structure were successfully fabricated using powder metallurgy and modified rapid prototyping (RP) process. The fabricated Ti scaffolds showed a highly porous structure with interconnected pores. The porosity and pore size of the scaffolds were in the range of 66$\sim$72% and $300\sim400\;\mu$m, respectively. The sintering of the fabricated scaffolds under the vacuum caused the Ti particles to bond to each other. The strength of the scaffolds depended on the layering patterns. The compressive strength of the scaffolds ranged from 15 MPa to 52 MPa according to the scaffolds' architecture. The alkali treatment of the fabricated scaffolds in an aqueous NaOH solution was shown to be effective in improving the bioactivity. The surface of the alkali-treated Ti scaffolds had a nano-sized fibre-like structure. The modified surface showed a good apatite forming ability. The apatite was formed on the surface of the alkali treated Ti scaffolds within 1 day. The thickness of the apatite increased when the soaking time in a simulated body fluid (SBF) solution increased. It is expected that the surface modification of Ti scaffolds by alkali treatment could be effective in forming apatites in vivo and can subsequently enhance bone formation.

Bioactivity-guided isolation of ginsenosides from Korean Red Ginseng with cytotoxic activity against human lung adenocarcinoma cells

  • Yu, Jae Sik;Roh, Hyun-Soo;Baek, Kwan-Hyuck;Lee, Seul;Kim, Sil;So, Hae Min;Moon, Eunjung;Pang, Changhyun;Jang, Tae Su;Kim, Ki Hyun
    • Journal of Ginseng Research
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    • v.42 no.4
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    • pp.562-570
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    • 2018
  • Background: Lung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells. Methods: Bioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively. Results and conclusion: Bioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate-soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with $IC_{50}$ values ranging from $161.1{\mu}M$ to $264.6{\mu}M$. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

In vitro biocompatibility of a cement compositecontaining poly ($\varepsilon$-caprolactonemicrosphere) (PCL)

  • Jyoti, Md. Anirban;Min, Young-Ki;Lee, Byong-Taek;Song, Ho-Yeon
    • Proceedings of the Materials Research Society of Korea Conference
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    • 2009.11a
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    • pp.42.1-42.1
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    • 2009
  • In recent years, it has been tried to develop the efficacy and bioactivity of Calcium Phosphate cements(CPC) as injectable bone substitute (IBS) by reinforcing them through varying the amount in its compositions and relative concentrations or adding other additives. In this study, the biocompatibility of are inforced Calcium Phosphate-Calcium Sulfate injectable bone substitute (IBS)containing poly ($\varepsilon$-caprolactone)PCL microspheres was evaluated which consisted of solution chitosan and Na-citrate as liquid phase and tetra calcium phosphate (TTCP), dicalciumphosphate anhydrous (DCPA) powder as the solid phase. The in vitrobiocompatibility of the IBS was done using MTT assay and Cellular adhesion and spreading studies. The in vitro experiments with simulated body fluid (SBF) confirmed the formation of apatite on sample surface after 7 and 14 days of incubation in SBF. SEM images for one cell morphologies showed that the cellular attachment was good. MG-63 cells were found to maintain their phenotype on samples and SEM micrograph confirmed that cellular attachment was well. In vitro cytotoxicity tests by an extract dilution method showed that the IBS was cytocompatible for fibroblast L-929.

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Synthesis and characterization of silk fibroin-bioactive glass hybrid xerogels

  • Wu, Xiaohong;Yan, Fuhua;Liu, Wei;Zhan, Hongbing;Yang, Wenrong
    • Biomaterials and Biomechanics in Bioengineering
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    • v.1 no.2
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    • pp.63-71
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    • 2014
  • This study aimed to develop a novel bioactive hybrid xerogel consisting of silk fibroin /$SiO_2-CaO-P_2O_5$ by sol-gel process at room temperature. Scanning electron microscopy (SEM), FT-IR Spectroscopy, pore measurement, mechanical property testing, in vitro bioactivity test and cytotoxicity assay were performed to characterize the xerogel for bone tissue engineering application. We have found that the xerogel possessed excellent pore structures and mechanical property. Once immersed in a simulated fluid (SBF), the xerogel exhibited profound bioactivity by inducing hydroxyapatite layers on its surfaces. The cell toxicity study also demonstrated that there was little toxic to MC3T3-E1 cells. These results indicate that silk fibroin /$SiO_2-CaO-P_2O_5$ hybrid xerogel potentially could be used as a bone tissue engineering material.