• 제목/요약/키워드: micro-migration

검색결과 116건 처리시간 0.044초

Angiogenesis in newly regenerated bone by secretomes of human mesenchymal stem cells

  • Katagiri, Wataru;Kawai, Takamasa;Osugi, Masashi;Sugimura-Wakayama, Yukiko;Sakaguchi, Kohei;Kojima, Taku;Kobayashi, Tadaharu
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제39권
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    • pp.8.1-8.8
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    • 2017
  • Background: For an effective bone graft for reconstruction of the maxillofacial region, an adequate vascular network will be required to supply blood, osteoprogenitor cells, and growth factors. We previously reported that the secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain numerous growth factors such as insulin-like growth factor (IGF)-1, transforming growth factor $(TGF)-{\beta}1$, and vascular endothelial growth factor (VEGF), which can affect the cellular characteristics and behavior of regenerating bone cells. We hypothesized that angiogenesis is an important step for bone regeneration, and VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic potential. In the present study, we focused on VEGF in MSC-CM and evaluated the angiogenic and osteogenic potentials of MSC-CM for bone regeneration. Methods: Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC-CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube formation was evaluated. For the evaluation of bone and blood vessel formation with micro-computed tomography (micro-CT) and for the histological and immunohistochemical analyses, a rat calvarial bone defect model was used. Results: The concentrations of IGF-1, VEGF, and $TGF-{\beta}1$ in MSC-CM were $1515.6{\pm}211.8pg/mL$, $465.8{\pm}108.8pg/mL$, and $339.8{\pm}14.4pg/mL$, respectively. Tube formation of HUVECs, bone formation, and blood vessel formation were increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group. Histological findings suggested that new bone formation in the entire defect was observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF group. Immunohistochemistry indicated that angiogenesis and migration of endogenous stem cells were much more abundant in the MSC-CM group than in the MSC-CM + anti-VEGF group. Conclusions: VEGF is considered a crucial factor in MSC-CM, and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration with angiogenesis.

PBT-6, a Novel PI3KC2γ Inhibitor in Rheumatoid Arthritis

  • Kim, Juyoung;Jung, Kyung Hee;Yoo, Jaeho;Park, Jung Hee;Yan, Hong Hua;Fang, Zhenghuan;Lim, Joo Han;Kwon, Seong-Ryul;Kim, Myung Ku;Park, Hyun-Ju;Hong, Soon-Sun
    • Biomolecules & Therapeutics
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    • 제28권2호
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    • pp.172-183
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    • 2020
  • Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.

Alteration of the Metabolome Profile in Endothelial Cells by Overexpression of miR-143/145

  • Wang, Wenshuo;Yang, Ye;Wang, Yiqing;Pang, Liewen;Huang, Jiechun;Tao, Hongyue;Sun, Xiaotian;Liu, Chen
    • Journal of Microbiology and Biotechnology
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    • 제26권3호
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    • pp.572-578
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    • 2016
  • Communication between endothelial cells (ECs) and smooth muscle cells (SMCs) via miR-143/145 clusters is vital to vascular stability. Previous research demonstrates that miR-143/145 released from ECs can regulate SMC proliferation and migration. In addition, a recent study has found that SMCs also have the capability of manipulating EC function via miR-143/145. In the present study, we artificially increased the expression of miR-143/145 in ECs, to mimic a similar change caused by miR-143/145 released by SMCs, and applied untargeted metabolomics analysis, aimed at investigating the consequential effect of miR-143/145 overexpression. Our results showed that miR-143/145 overexpression alters the levels of metabolites involved in energy production, DNA methylation, and oxidative stress. These changed metabolites indicate that metabolic pathways, such as the SAM cycle and TCA cycle, exhibit significant differences from the norm with miR-143/145 overexpression.

결혼이민자 가족을 위한 임파워먼트 기반의 사회복지실천 연구 (Social Work with Marriage Based Immigrant Families: an Application of Empowerment Approach)

  • 윤혜미
    • 한국사회복지학
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    • 제61권4호
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    • pp.85-108
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    • 2009
  • 본 연구는 결혼이민자 가족이 직면하고 있는 다양한 도전에 대해 사회복지실천현장의 효과적인 접근방법으로 임파워먼트 접근의 틀을 제시하고자 하였다. 구체적으로 첫째, 결혼이민여성의 프로필과 지원서비스현황을 파악하고, 둘째, 적응관련 쟁점을 정리하였다. 셋째, 적응쟁점을 개인과 가족 관계, 지역사회 관련 및 사회문화 관련으로 구분하고, 임파워먼트 기반 사회복지실천 접근의 내용을 각각의 쟁점별로 거시 중도 미시적 수준에서 논의하였다. 결혼이민자 가족을 위한 차별화된 접근은 다문화역량과 밀접한 관계에 있다고 보고, 사회복지사 자신과 사회복지기관, 지역사회의 문화적 편견에 대한인식과 다문화 지식 및 기술의 개발 필요성을 지적하였다. 끝으로 다문화역량 확보에 대한 사회복지학계와 실천현장의 대응에 대해 논의하였다.

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Fe-Ni-Co 코바 합금의 고온변형거동에 미치는 합금원소(Mn, Mo, B) 첨가의 영향 (Effect of Alloying Elements(Mn, Mo, B) on the High Temperature Deformation Behavior of Low Thermal Expansion Fe-Ni-Co Alloy)

  • 이기안;윤애천;박중철;남궁정;김문철
    • 소성∙가공
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    • 제17권4호
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    • pp.240-248
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    • 2008
  • The effect of alloying elements(Mn, S, Mo, B) on the high temperature deformation behavior of Fe-29%Ni-17%Co (Kovar) alloy were investigated. And the effect of high temperature oxidation on the hot ductility was also studied. The hot ductility of Kovar alloy was drastically increased with the addition of Mn and lowering of S content. It has been found that the brittle intergranular fracture at high temperature cracking is closely associated with the FeS sulfide along the grain boundary. When Mn was added, the type of sulfide was changed to MnS from FeS and ductile intergranular fracture and transgranular fracture were promoted. The formation of oxide layer was found to have minimized the hot ductility of the Kovar alloy significantly. Grain boundary micro-cracks in the internal oxide region were noted following deformation due to high temperature, one of which acting as a notch that caused the poor hot workability of the oxidized specimen. The addition of Mo to the Kovar alloy could also retard the decrease in the hot ductility of the oxidized specimen through the prevention of notching due to internal oxidation. Hot ductility was remarkably improved by the addition of Boron. The improvement of hot ductility results from the grain boundary migration mainly due to the dynamic recrystallization at lower temperature range ($900{\sim}1000^{\circ}C$).

수중둔덕의 이동율 예측을 위한 해석해 (Analytical Solutions for Predicting Movement Rate of Submerged Mound)

    • 한국해안해양공학회지
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    • 제10권4호
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    • pp.165-173
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    • 1998
  • 파고와 주기 그리고 수심의 함수로 정의된 이류계수를 파고와 주기에 대한 결합분포함수와 확률적으로 결합하여 수중둔덕의 이동율을 예측할 수 있는 해석해를 유도하였다. 파랑의 비선형성에 의하여 유발되는 하상에서의 흐름이 표사의 이동을 유발한다는 가정하에 개념적 모형의 표사이동량 방정식을 사용하였다. 표사보존식에 표사이동량을 대입하여 시간에 따른 해저면의 변동을 나타내는 비선형 이류-확산 방정식을 얻을 수 있었다. 해석해에 의하면 수심이 증가할 수록 수중둔덕의 이동율은 지수적으로 감소하는 경향을 보였다. 그러나 스펙트럼에서 주파수 영역의 폭을 정의하는 계수, v의 값이 커지면 수중둔덕의 이동율은 증가하였다. 해석해에 의하여 예측된 수중둔덕의 이동율은 관측자료보다 과대평가하는 경향을 나타내나, 해석해를 유도하는 과정에 내포된 이론식의 제약성 및 입력자료의 부정확성 등을 고려할 때 전반적으로 해석해의 결과는 관측자료와 잘\ulcorner 일치한다고 볼 수 있다. 특히, 수심의 변화에 따른 해석해의 거동은 대상영역 외해에서 추정된 자료를 이용하여 이산화 기법으로 추정된 결과와 매우 잘 일치하였다.

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DNA Comet Assay를 이용한 방사선 조사 쇠고기와 돼지고기의 검지 기술 (Detection of Irradiated Beef and Pork by DNA Comet Assay)

  • 박준영;오경남;김경은;양재승
    • 한국식품영양과학회지
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    • 제29권6호
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    • pp.1025-1029
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    • 2000
  • 방사선 조사된 쇠고기와 돼지고기의 방사선 조사 여부를 판별하는데 DNA comet assay의 활용 가능성을 검토하였다. 쇠고기와 돼지고기는 Co-60 동위 원소를 조사원으로 하여 0.1, 0.3, 0.5, 0.7, 1.0 kGy의 총흡수선량( $\pm$ 5.0%)이 되도록 조사하여, 냉동상태로 보관하였다. 시료로부터 분리 된 세포는 agarose gel과 혼합하여 슬라이드에 깔아주고, lysis 및 전기영동을 하였다. 방사선 조사된 시료의 경우 세포로부터 끌려나오는 DNA절편들은 양극을 방향으로 tail이 형성되었고, 비조사 시료의 경우 tail이 없거나, 일부에서만 작은 tail이 관찰되었다. 방사선 조사유무는 0.1 kGy부터 현미경상으로 검지가 가능하였고, 선량간 차이의 유의성 여부는 통계분석을 통하여 검지가 가능하여, 쇠고기와 돼지고기의 신속한 검지 방법으로 DNA comet assay를 활용할 수 있을 것이다.

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Endothelial miR-26a regulates VEGF-Nogo-B receptor-mediated angiogenesis

  • Jo, Ha-neul;Kang, Hyesoo;Lee, Aram;Choi, Jihea;Chang, Woochul;Lee, Myeong-Sok;Kim, Jongmin
    • BMB Reports
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    • 제50권7호
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    • pp.384-389
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    • 2017
  • The Nogo-B receptor (NgBR) is necessary for not only Nogo-B-mediated angiogenesis but also vascular endothelial growth factor (VEGF) -induced angiogenesis. However, the molecular mechanisms underlying the regulatory role of the VEGF-NgBR axis in angiogenesis are not fully understood. Here, we report that miR-26a serves as a critical regulator of VEGF-mediated angiogenesis through directly targeting NgBR in endothelial cells (ECs). Stimulation of ECs by VEGF increased the expression of NgBR and decreased the expression of miR-26a. In addition, miR-26a decreased the VEGF-induced migration and proliferation of ECs. Moreover, miR-26a overexpression in ECs decreased the VEGF-induced phosphorylation of the endothelial nitric oxide synthase (eNOS) and the production of nitric oxide, which is important for angiogenesis. Overall, these data suggest that miR-26a plays a key role in VEGF-mediated angiogenesis through the modulation of eNOS activity, which is mediated by its ability to regulate NgBR expression by directly targeting the NgBR 3'-UTR.

MiR-374b Promotes Proliferation and Inhibits Apoptosis of Human GIST Cells by Inhibiting PTEN through Activation of the PI3K/Akt Pathway

  • Long, Zi-Wen;Wu, Jiang-Hong;Hong, Cai;Wang, Ya-Nong;Zhou, Ye
    • Molecules and Cells
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    • 제41권6호
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    • pp.532-544
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    • 2018
  • Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

Backbone NMR assignments of the FAS1-3/FAS1-4 domains of transforming growth factor-beta-induced protein

  • Kang, Dong-Hoon;Yi, Jong-Jae;Sim, Dae-Won;Park, Jung-Wook;Lee, Sung-Hee;Kim, Eun-Hee;Jeon, Young-Ho;Son, Woo Sung;Won, Hyung-Sik;Kim, Ji-Hun
    • 한국자기공명학회논문지
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    • 제24권1호
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    • pp.1-8
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    • 2020
  • An extracellular matrix protein, transforming growth factor-beta-induced protein (TGFBIp/βig-h3), which is induced by transforming growth factor-β in the human cornea, skin, and matrix of many connective tissues, is associated with the adhesion, migration, proliferation, and differentiation of various cells. TGFBIp contains four homologous repeat domains, known as FAS1 domains, where certain mutations have been considered to cause corneal dystrophies. In this study, backbone NMR assignments of FAS1-3/FAS1-4 tandem domain were obtained and compared with those previously known for the isolated FAS1-4 domain. The results corroborate in solution the inter-domain interaction between FAS1-3 and FAS1-4 in TGFBIp.