• 제목/요약/키워드: proliferation, migration

검색결과 587건 처리시간 0.028초

Dronedarone hydrochloride enhances the bioactivity of endothelial progenitor cells via regulation of the AKT signaling pathway

  • Zhang, Jian;Le, Thi Hong Van;Rethineswaran, Vinoth Kumar;Kim, Yeon-Ju;Jang, Woong Bi;Ji, Seung Taek;Ly, Thanh Truong Giang;Ha, Jong Seong;Yun, Jisoo;Cheong, Jae Hun;Jung, Jinsup;Kwon, Sang-Mo
    • The Korean Journal of Physiology and Pharmacology
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    • 제25권5호
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    • pp.459-466
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    • 2021
  • Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.

매실 부탄올 분획물에 의한 혈관 신생 억제 효과 (Angiogenesis-inhibiting Effects of Prunus mume Butanol Fractions on Human Umbilical Vein Endothelial Cells)

  • 민혜지;김정호;허지안;원영선;서권일
    • 생명과학회지
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    • 제31권1호
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    • pp.59-65
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    • 2021
  • Prunus mume Sieb. et Zucc는 아시아 전역에 분포되어 있으며 전통적으로 약과 음식에 사용되어져 왔다. 이러한 매실은 각종 유기산, 무기질 및 페놀성분이 다량으로 함유되어 있는 것으로 알려져 있다. 지금까지의 매실 연구 동향은 항산화, 항암, 항균 등의 연구에만 치중되어 있고 혈관 신생에 대한 연구는 거의 이루어져 있지 않다. 혈관 신생은 전이성 암의 일반적인 특징으로 이를 통하여 부족한 산소와 영양분을 타 조직에서 가지고 온다. 이 연구에서는 매실 부탄올 분획물의 총 폴리페놀 및 플라보노이드 함량과 VEGF로 유도된 인체 혈관 내피 세포의 증식과 이동성, 침윤 및 모세혈관 형성 억제능을 평가함으로서 혈관신생 억제 활성에 대하여 조사하였다. 매실 부탄올 분획물은 높은 항산화능을 가지고 있는 폴리페놀(12.81 mg GAE/g)과 플라보노이드(28.4 mg QE/g)를 함유하고 있다. 매실 부탄올 분획물은 25-200 ㎍/ml의 농도에서 인체 혈관 내피 세포의 증식을 억제하지 않았으며 정상 세포에 독성을 나타내지 않았다. 또한 매실 부탄올 분획물은 인체 혈관 내피 세포에서 VEGF에 의한 이동성, 침윤 및 모세혈관 형성을 억제하였다. 이 결과는 매실 부탄올 분획물이 VEGF에 의해 유도된 인체 혈관 내피 세포의 혈관 신생활성을 억제하는 것을 시사하였다. 따라서 본 연구는 매실 부탄올 분획물이 혈관 신생 억제를 위한 잠재적인 치료제로서의 가능성이 있음을 확인하였다.

혈소판유래성장인자-BB가 골간질세포와 치주인대세포의 성상에 미치는 영향 (A study of the effects of PDGF-BB on the characteristics of bone stromal and periodontal ligament cells)

  • 권영혁;박준봉
    • Journal of Periodontal and Implant Science
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    • 제26권4호
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    • pp.949-965
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    • 1996
  • The main goal of periodontal therapy is to restore the lost periodontal tissue and establish the attachment appratus. Current acceptable therapeutic techniques are included : removal of diseased soft tissue, demineralization of exposed root surface, using the barrier membrane for preventing the downgrowth of gingival epithelial cell, insertion of graft materials as a scaffolding action, and biological mediators for promoting the cell activity. The latest concept one among them has been studied which based on the knowledge of cellular biology of destructed tissue. Platelet-derived growth factor(PDGF) is one of the polypeptide growth factor which have been reported as a biological mediator to regulate activities of wound healing progress including cell proliferation, migration, and metabolism. The purposes of this study is to evaluate the influences of the PDGF as biological mediator to periodontal ligament and bone marrow cell. Both right and left maxillary first molar were extracted from rat which had treated with 0.4% ${\beta}-Aminopropionitril$ for 5 days, and feeded until designed date to sacrifice under anesthesisa. Periodontal ligament were removed from the extracted socket of the rat, and cultured with Dulbecco's Modified Essential Medium(DMEM) contained with 10% Fetal Bovine Serum, 100U/ml penicillin, $100{\mu}g/ml$ streptomycin, $0.5{\mu}g/ml$ amphotericin-B. Bone marrow cell were culture from bone marrow suspension with which washed out from femur with same medium. The study was performed to evaluate the effect of PDGF to periodontal ligament and bone cell, cell proliferation rate, total protein synthesis, and alkaline phosphatase activity of rat periodontal ligament(PDL) cell and bone stromal(RBS) cell in vitro. The effects of growth factors on both cells were measured at 3, 5th day after cell culture with (control group) or without growth factors(experimental group). The results were as follows: 1. The tendency of cell proliferation under the influence of PDGF showed more rapid proliferation pattern than control at 3 and 5 days after inoculation. 2. The activity of Alkaline phosphatase revealed 14, 80% increased respectively at 3, 5 days culture than control group. Measurements of ALPase levels indicated that PDL cells had significantly higher activity when compared with that of co-culture groups and GF only(P<0.05). And, ALPase activity in 10 days was higher than that of 7 days(P<0.05). 3. The tendency of formation of the mineralized nodule were observed dose-depend pattern of PDL cells. There was statistically significant difference among group l(PDL 100%), 2(PDL 70%:GF 30%), and 3(PDL 50%:GF 50%)(P<0.01). But, there was no difference among group 3, 4(PDL 30%:GF 70%), and 5(GF 100%). 4. Also, the number of nodule was greater in co-culture of PDL 70% and GF 30% than in culture of PDL 70%(P<0.05). From the above results, it is assumed that the PDGF on PDL cells and RMB cell culture. GF stimulates the cell growth, which is not that of PDL cells but GF. And, the activity of ALPase depends on the ratio of PDL cells, and ALPase may relate to the initial phase of nodule formation. Also, it is thought that the calcified nodule formation principally depends on PDL cells, is inhibited by GF, and affected by cell density. In conclusion, platelet-derived growth factor can promote rapid osteogenesis during early stage of periodontal tissue regeneration.

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Calcium sulfate와 혈소판 유래성장인자의 혼합사용이 치주인대세포에 미치는 영향 (The effects of a combination of calcium sulfate and platelet-derived growth factor on periodontal ligament cells in vitro)

  • 김준성;최성호;유윤정;채중규;김종관;조규성
    • Journal of Periodontal and Implant Science
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    • 제27권4호
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    • pp.785-804
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    • 1997
  • It was well known that calcium sulfate was biocompatible, resorbed rapidly in the body, had potential as a good barrier membrane. Platelet-derived growth factor(PDGF) was one of polypeptide growth factor that had been reported as a biological mediator which regulates activities of wound healing process including the cell proliferation, migration and metabolism. The purpose of this study was to evaluate the effects of a combination of calcium sulfate and PDGF on periodontal ligament cells in vitro to use as a regeneration promoting agent of periodontal tissue. Human periodontal ligament cells were prepared from the premolar tooth extracted for the orthodontic treatment. Cells were cultured in ${\alpha}-MEM$ contained with 20% FBS, at the $37^{\circ}C$, 100% of humidity, 5% $Co_2$ incubator. Cells were inoculated and cultured into 96 well culture plate with $1{\times}10^4cells/well$ of ${\alpha}-MEM$ for 1 day. After discarding the medium, those cells were cultured in ${\alpha}-MEM$ contained with 10% FBS alone(control group), in calcium sulfate(calcium sulfate group), in calcium sulfate treated with 15ng/ml of PDGF-BB(calcium sulfate+PDGF group), in ${\alpha}-MEM$ contained with 10% FBS treated with 15ng/ml of PDGF-BB(PDGF group) for 1, 2, 3 day respectively. And then each group was characterized by examining of the cell counting, MTT assay, collagen synthesis. The results were as follows. 1. In the analysis of cell proliferation by cell counting, both calcium sulfate group and calcium sulfate plus PDGF group showed no stastically significant difference compared to control group, but there was stastically significant difference between PDGF group and calcium sulfate group at 1, 2 day(P<0.05). 2. In the analysis of cell proliferation by MTT assay in calcium sulfate extracts, both calcium sulfate group and calcium sulfate plus PDGF group showed no stastically significant difference compared to control group, but there was stastically significant difference between PDGF group and calcium sulfate group at 2, 3 day, and between calcium sulfate plus PDGF group and calcium sulfate group at 2 day(P

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인간 폐섬유아세포에서 TGF-β 자극에 의한 VEGF 분비 (Transforming growth factor-β promoted vascular endothelial growth factor release by human lung fibroblasts)

  • 박상욱;신주화;심재원;김덕수;정혜림;박문수;심정연
    • Clinical and Experimental Pediatrics
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    • 제51권8호
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    • pp.879-885
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    • 2008
  • 목 적 : 폐섬유아세포는 예전에는 기도의 구조적 세포로만 알려져 왔으나, 최근에는 천식에서 기관지 운동의 톤을 조절할 뿐만 아니라 기도의 면역조절과 기도 개형에서 중요한 역할을 하는 것으로 밝혀지고 있다. VEGF는 혈관 내피세포에서 강력한 작용을 하는 다기능적 사이토카인으로서, 상피내 세포의 세포분열을 유도하고, 상피세포의 투과도를 증가시키며, 상피세포의 이동을 향상시키는 역할을 하는 것으로 알려져 있다. TARC는 Th2 세포의 선택적 이동을 유도하는 케모카인으로 알려져 있다. 본 연구에서는 PDGF와 TGF-${\beta}$로 자극시킨 인간 폐섬유아세포에서 VEGF와 TARC가 생성되는지와 dexamethasone이 폐섬유아세포에서 VEGF의 분비를 억제하는지를 알아보고자 하였다. 또한 폐섬유아세포와 기관지 평활근 세포와 함께 배양했을 때 VEGF 생성에 미치는 효과를 단독배양 시와 비교하였다. 방 법 : 폐섬유아세포와 인간 기관지 평활근세포를 각각 혹은 함께 배양한 뒤 48시간동안 무혈청 배지에서 성장을 정지시킨 후 TGF-${\beta}$ (10 ng/mL)와 PDGF (20 ng/mL)로 자극하였다. 자극 후의 세포 증식 반응과 배양액 상층액의 VEGF, TARC 농도를 측정하여 dexamethasone ($10^{-6}M$)으로 전처치 후 자극한 것과 비교하였다. 결 과 : PDGF와 TGF-${\beta}$로 자극하였을 경우 폐섬유아세포에서 VEGF 분비가 의미있게 증가하였고, 특히 PDGF와 TGF-${\beta}$로 함께 자극하였을 경우 더욱 의미있는 상승을 보였다. Dexamethasone은 폐섬유아세포의 VEGF 분비를 PDGF로 자극한 경우와 PDGF, TGF-${\beta}$ 같이 자극한 경우 모두에서 억제하였다. 인간 기관지 평활근 세포와 폐섬유아세포를 혼합 배양했을 때 VEGF 분비에는 상승적인 효과가 없었다. Dexamethasone은 폐섬유아세포 증식을 억제시키지 않았다. 폐섬유아세포를 PDGF와 TGF-${\beta}$로 자극했을 때 TARC는 분비되지 않았다. 결 론 : 폐섬유아세포는 VEGF 분비를 통해 기도 개형에 관여하며, 기관지 평활근 세포와 함께 배양해도 VEGF 분비에 상승 효과는 없다. Dexamethasone은 VEGF 분비를 억제하였으나 폐섬유아세포의 증식을 억제하지는 못하였다.

고혈압-연관 단백질 부활효소 C의 활성과 물리치료의 상관성 (The Activity of Hypertension-related Protein Kinase C and the Relationship of Physical Therapy)

  • 김중환
    • The Journal of Korean Physical Therapy
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    • 제20권3호
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    • pp.61-68
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    • 2008
  • Purpose: Protein kinase C (PKC) is a member of a family of serine/threonine kinases that are activated by diacylglycerol (DG) and PKC stimulants. PKC play a key role in signal transduction, including muscle contraction, cell migration, apoptosis, cell proliferation and differentiation. However, the mechanism relating mitogen-activated protein kinases (MAPKs) and PKC, especially in the volume-dependent hypertensive state, remains unclear. Methods: In the present study, I investigated the relationship between PKC and MAPKs for isometric contraction, PKC translocation, and enzymatic activity from normotensive sham-operated rats (NSR) and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive rats (ADHR). Results: Systolic blood pressure was significantly increased in ADHR than in NSR. Physiological salt solution (PSS)-induced resting tension and the intracellular $Ca^{2+}$ concentration ([$Ca^{2+}{_i}$]) were different in the ADHR and NSR. The expression of PKC$\alpha$, PKC$\beta$II, PKC$\delta$, PKC$\varepsilon$ and PKC$\xi$ were different between the cytoplasmic and membranous fractions. However, expression of the PKC isoforms did not differ for the ADHR and NSR. The use of 12-deoxyphorbol 13-isobutyrate (DPB, a PKC stimulant) induced isometric contraction in $Ca^{2+}$-free medium, which was diminished in muscle strips from ADHR as compared to NSR. Increased vasoconstriction and phosphorylation induced by the use of 1 ${\mu}$M DPB were inhibited by treatment with 10 ${\mu}$M PD098059 and 10 ${\mu}$M SB203580, inhibitors of extracellular-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK from ADHR, respectively. Conclusion: These results suggest that the development of aldosterone analogue-induced hypertension is associated with an altered blood pressure, resting tension, [$Ca^{2+}{_i}$], and that the $Ca^{2+}$-independent contraction evoked by PKC stimulants is due to the activation of ERK1/2 and p38 MAPK in volume-dependent hypertension. Therefore, it is suggested that PKC activity affects volume-dependent hypertension and the need to develop cardiovascular disease-specialized physical therapy.

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Geft is dispensable for the development of the second heart field

  • Fan, Xiongwei;Hou, Ning;Fan, Kaiji;Yuan, Jiajia;Mo, Xiaoyang;Deng, Yun;Wan, Yongqi;Teng, Yan;Yang, Xiao;Wu, Xiushan
    • BMB Reports
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    • 제45권3호
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    • pp.153-158
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    • 2012
  • Geft is a guanine nucleotide exchange factor, which can specifically activate Rho family of small GTPase by catalyzing the exchange of bound GDP for GTP. Geft is highly expressed in the excitable tissue as heart and skeletal muscle and plays important roles in many cellular processes, such as cell proliferation, migration, and cell fate decision. However, the in vivo role of Geft remains unknown. Here, we generated a Geft conditional knockout mouse by flanking exons 5-17 of Geft with loxP sites. Cre-mediated deletion of the Geft gene in heart using Mef2c-Cre transgenic mice resulted in a dramatic decrease of Geft expression. Geft knockout mice develop normally and exhibit no discernable phenotype, suggesting Geft is dispensable for the development of the second heart field in mouse. The Geft conditional knockout mouse will be a valuable genetic tool for uncovering the in vivo roles of Geft during development and in adult homeostasis.

HQSAR Study on Substituted 1H-Pyrazolo[3,4-b]pyridines Derivatives as FGFR Kinase Antagonists

  • Bhujbal, Swapnil P.;Balasubramanian, Pavithra K.;Keretsu, Seketoulie;Cho, Seung Joo
    • 통합자연과학논문집
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    • 제10권2호
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    • pp.85-94
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    • 2017
  • Fibroblast growth factor receptor (FGFR) belongs to the family of receptor tyrosine kinase. They play important roles in cell proliferation, differentiation, development, migration, survival, wound healing, haematopoiesis and tumorigenesis. FGFRs are reported to cause several types of cancers in humans which make it an important drug target. In the current study, HQSAR analysis was performed on a series of recently reported 1H-Pyrazolo [3,4-b]pyridine derivatives as FGFR antagonists. The model was developed with Atom (A) and bond (B) connection (C), chirality (Ch), hydrogen (H) and donor/acceptor (DA) parameters and with different set of atom counts to improve the model. A reasonable HQSAR model ($q^2=0.701$, SDEP=0.654, NOC=5, $r^2=0.926$, SEE=0.325, BHL=71) was generated which showed good predictive ability. The contribution map depicted the atom contribution in inhibitory effect. A contribution map for the most active compound (compound 24) indicated that hydrogen and nitrogen atoms in the side chains of ring B as well as hydrogen atoms in the side chain of ring C and the nitrogen atom in the ring D contributed positively to the activity in inhibitory effect whereas, the lowest active compound (compound 04) showed negative contribution to inhibitory effect. Thus results of our study can provide insights in the designing potent and selective FGFR kinase inhibitors.

The first review study on association of DNA methylation with gastric cancer in Iranian population

  • Shahbazi, Mahsa;Yari, Kheirollah;Rezania, Niloufar
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권5호
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    • pp.2499-2506
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    • 2016
  • Background: Gastric cancer (GC) is the second leading cause of cancer-related death worldwide. Several environmental, genetic and epigenetic factors have been suggested to have a role in GC development. Epigenetic mechanisms like histone changes and promoter hyper-methylation are now being increasingly studied. Associations between methylation of many gene promoters with the risk of gastric cancer have been investigated worldwide. Such aberrant methylation may result in silencing of specific genes related to cell cycling, cell adhesion, apoptosis and DNA repair. Thus this molecular mechanism might have a key role in proliferation and migration of cancerous cells. Materials and Methods: In this review article we included studies conducted on DNA methylation and gastric cancer in Iranian populations. Using Science direct, Pubmed/PMC, Springer, Wiley online library and SciELO databases, all published data until 31 January 2016 were gathered. We also searched Science direct data base for similar investigations around the world to make a comparison between Iran and other countries. Results: By searching these databases, we found that the association between methylation of seven gene promoters and gastric cancer had been studied in Iran until 31 January 2016. These genes were p16, hLMH1, E-cadherin, CTLA4, $THR{\beta}$, mir9 and APC. Searching in science direct database also showed that 92 articles had been published around the world till January 2016. Our investigation revealed that despite the importance of GC and its high prevalence in Iran, the methylation status of only a few gene promoters has been studied so far. More studies with higher sample numbers are needed to reveal the relation of methylation status of gene promoters to gastric cancer in Iran. Conclusions: Further studies will be helpful in identifying associations of DNA methylation in candidate genes with gastric cancer risk in Iranian populations.

Exosomes derived from microRNA-584 transfected mesenchymal stem cells: novel alternative therapeutic vehicles for cancer therapy

  • Kim, Ran;Lee, Seokyeon;Lee, Jihyun;Kim, Minji;Kim, Won Jung;Lee, Hee Won;Lee, Min Young;Kim, Jongmin;Chang, Woochul
    • BMB Reports
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    • 제51권8호
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    • pp.406-411
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    • 2018
  • Exosomes are small membranous vesicles which contain abundant RNA molecules, and are transferred from releasing cells to uptaking cells. MicroRNA (miRNA) is one of the transferred molecules affecting the adopted cells, including glioma cells. We hypothesized that mesenchymal stem cells (MSCs) can secrete exosomes loading miRNA and have important effects on the progress of gliomas. To determine these effects by treating exosomal miRNA in culture media of miRNA mimic transfected MSCs, we assessed the in vitro cell proliferation and invasion capabilities, and the expression level of relative proteins associated with cell apoptosis, growth and migration. For animal studies, the mice injected with U87 cells were exposed to exosomes derived from miRNA-584-5p transfected MSCs, to confirm the influence of exosomal miRNA on the progress of glioma. Based on our results, we propose a new targeted cancer therapy wherein exosomes derived from miRNA transfected MSCs could be used to modulate tumor progress as the anticancer vehicles.