• Title/Summary/Keyword: Tissue factor

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Zebrafish Klf11b is Required to Maintain Cell Viability by Inhibiting p53-Mediated Apoptosis

  • Kong, Hee Jeong;Lee, Jung Jin;Kim, Ju-Won;Kim, Julan;Kim, Young-Ok;Yeo, Sang-Yeob
    • Development and Reproduction
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    • v.26 no.2
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    • pp.79-90
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    • 2022
  • Krüppel-like factor 10 (KLF10) regulates various cellular functions, such as proliferation, differentiation and apoptosis, as well as the homeostasis of several types of tissue. In the present study, we attempted a loss-of-function analysis of zebrafish Klf11a and Klf11b, which constitute human KLF10 homologs. Embryos injected with klf11b-morpholino (MO) showed developmental retardation and cell death, whereas klf11a-MO-injected embryos showed normal development. In klf11b-MO-injected embryos, a dramatic increase in the amount of zebrafish p53 mRNA might be the cause of the increase in that of bax. The degree of apoptosis decreased in the klf11b-MO and p53-MO co-injected embryos. These findings imply that KLF10 is a negative regulator of p53-dependent transcription, suggesting that the KLF10/p53 complex may play an important role in apoptosis for maintenance of tissue homeostasis during embryonic development.

Protective Effects of BCC Against Oxidative Stress in Cardiomyocyte Cells

  • Bong-Geun Shin;Dae-Kwan Kim
    • Biomedical Science Letters
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    • v.30 no.1
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    • pp.10-16
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    • 2024
  • Oxidative stress caused by elevated reactive oxygen species (ROS) in the heart causes various heart diseases. Oxidative stress is known as a factor that causes diseases in various organs as well as the heart. Diseases such as heart failure, myocardial infarction, and cardiomyopathy caused by oxidative stress in the heart can be treated with medication or surgery. Recently, blood cells concentrate (BCC) is used in various treatment areas such as orthopedics, gynecology, and urology. BCC therapy is applied to treatment by concentrating platelets and white blood cells necessary for regeneration through simple centrifugation using autologous blood. As the platelets are activated, many growth factors are released from alpha granules of the platelets. Growth factors such as TGF-β1, PDGF, VEGF, and EGF derived from platelets are involved in various cell signaling pathway. Due to these growth factors, BCC can contribute to tissue regeneration and can treat various diseases. CD34+ cells contained in BCC may also play an important role in tissue regeneration. In this study, we investigated whether BCC has a regenerative effect on heart disease, and if so, what mechanism causes the effect. To observe this, cardiomyocyte cells were treated with H2O2 to induce oxidative stress. And the effect was confirmed in the presence or absence of BCC. As a result, in the presence of BCC, the oxidative stress of cardiomyocyte cells was reduced and cell damage was also reduced. These results suggest that BCC therapy can be a new treatment alternative for heart disease.

Effect of seeding using an avidin-biotin binding system on the attachment of periodontal ligament fibroblasts to nanohydroxyapatite scaffolds: three-dimensional culture

  • Jang, Yong-Ju;Jung, Im-Hee;Park, Jung-Chul;Jung, Ui-Won;Kim, Chang-Sung;Lee, Yong-Keun;Kim, Chong-Kwan;Choi, Seong-Ho
    • Journal of Periodontal and Implant Science
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    • v.41 no.2
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    • pp.73-78
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    • 2011
  • Purpose: For periodontal tissue engineering, it is a primary requisite and a challenge to select the optimum types of cells, properties of scaffold, and growth factor combination to reconstruct a specific tissue in its natural form and with the appropriate function. Owing to fundamental disadvantages associated with using a two-dimensional substrate, several methods of seeding cells into three-dimensional scaffolds have been reported and the authors have asserted its usefulness and effectiveness. In this study, we explore the cell attachment of periodontal ligament fibroblasts on nanohydroxyapatite (n-HA) scaffold using avidin biotin binding system (ABBS). Methods: Human periodontal ligament fibroblasts were isolated from the health tooth extracted for the purpose of orthodontic procedure. HA nanoparticles were prepared and $Ca(NO_3)_2-_4H_2O$ and $(OC_2H_5)_3P$ were selected as precursors of HA sol. The final scaffold was 8 mm in diameter and 3 mm in height disk with porosity value of 81.55%. $1{\times}10^5$ periodontal ligament fibroblasts were applied to each scaffold. The cells were seeded into scaffolds by static, agitating and ABBS seeding method. Results: The number of periodontal ligament fibroblasts attached was greater for ABBS seeding method than for static or agitating method (P<0.05). No meaningful difference has been observed among seeding methods with scanning electron microscopy images. However, increased strength of cell attachment of ABBS could be deduced from the high affinity between avidin and biotin ($Kd=10^{-15}\;M$). Conclusions: The high-affinity ABBS enhances the ability of periodontal ligament fibroblasts to attach to three-dimensionally constructed n-HA scaffold.

The Neovascularization Effect of Bone Marrow Stromal Cells in Temporal Muscle after Encephalomyosynangiosis in Chronic Cerebral Ischemic Rats

  • Kim, Hyung-Syup;Lee, Hyung-Jin;Yeu, In-Seung;Yi, Jin-Seok;Yang, Ji-Ho;Lee, Il-Woo
    • Journal of Korean Neurosurgical Society
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    • v.44 no.4
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    • pp.249-255
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    • 2008
  • Objective : In Moyamoya disease, the primary goal of treatment is to improve collateral circulation through angiogenesis. In the present study, we obtained and sub-cultured bone marrow stromal cells (BMSCs) from rats without a cell-mediated immune response. Then, we injected the labeled BMSCs directly into adjacent temporal muscle during encephalomyosynangiosis (EMS). Three weeks after BMSC transplantation, we examined the survival of the cells and the extent of neovascularization. Methods : We divided 20 rats into a BMSC transplantation group (n=12) and a control group (n=8). Seven days after the induction of chronic cerebral ischemia, an EMS operation was performed, and labeled BMSCs ($1{\times}106^6/100\;{\mu}L$) were injected in the temporal muscle for the transplantation group, while an equivalent amount of culture solution was injected for the control group. Three weeks after the transplantation, temporal muscle and brain tissue were collected for histological examination and western blot analysis. Results : The capillary/muscle ratio in the temporal muscle was increased in the BMSC transplantation group compared to the control group, showing a greater increase of angiogenesis (p<0.05). In the brain tissue, angiogenesis was not significantly different between the two groups. The injected BMSCs in the temporal muscle were vascular endothelial growth factor (VEGF)-positive by immunofluorescence staining. In both temporal muscle and brain tissue, the expression of VEGF by western blot analysis was not much different between the two groups. Conclusion : During EMS in a chronic cerebral ischemia rat model, the injection of BMSCs resulted in accelerated angiogenesis in the temporal muscle compared to the control group.

Identification of ANXA1 as a Lymphatic Metastasis and Poor Prognostic Factor in Pancreatic Ductal Adenocarcinoma

  • Liu, Qing-Hua;Shi, Mei-Lin;Bai, Jin;Zheng, Jun-Nian
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2719-2724
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    • 2015
  • Objective: The aim of this study was to investigate the clinical significance of annexin a1 (ANXA1) and provide molecular evidence to support that decreased ANXA1 expression could enhance cancer migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: Immunohistochemistry of a tissue microarray with 162 surgically resected PDAC specimens was performed to examine the expression of ANXA1. We also investigated the relationship between ANXA1 expression and clinicopathological factors and prognosis of PDAC patients. We further studied the role of ANXA1 in PDAC cell proliferation, migration and invasion by cell proliferation assay, migration assay and matrigel invasion assay with reduced ANXA1 expression by RNAi. Western blotting was used to detect matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. We also detected MMP-9 enzyme activity by gelatin zymography. Results: Decreased expression of ANXA1 was significantly associated with poor differentiation, lymph node metastasis and advanced TNM stage of PDAC patients (p<0.05). Moreover, decreased expression of ANXA1 was correlated with poor survival (p<0.05). Furthermore, we found that ANXA1 knockdown inhibited cell proliferation, induced G1 phase cell cycle arrest, increased PDAC cell migration and invasion capacity compared with controls. In addition, Western blotting showed that ANXA1 knockdown increased the MMP-9 protein level and decreased TIMP-1 expression. Gelatin zymography showed that MMP-9 enzyme activity was also elevated. Conclusions: Negative ANXA1 expression is a most unfavorable prognostic factor for PDAC patients. ANXA1 knockdown inhibits cell proliferation by inducing G1 phase cell cycle arrest and increases migration and invasion of PDAC cells through up-regulating MMP-9 expression and activity, implying that ANXA1 may serve as a promising prognostic biomarker and therapeutic target for PDAC.

Transforming Growth Factor-β-Induced RBFOX3 Inhibition Promotes Epithelial-Mesenchymal Transition of Lung Cancer Cells

  • Kim, Yong-Eun;Kim, Jong Ok;Park, Ki-Sun;Won, Minho;Kim, Kyoon Eon;Kim, Kee K.
    • Molecules and Cells
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    • v.39 no.8
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    • pp.625-630
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    • 2016
  • The RNA-binding protein Rbfox3 is a well-known splicing regulator that is used as a marker for post-mitotic neurons in various vertebrate species. Although recent studies indicate a variable expression of Rbfox3 in non-neuronal tissues, including lung tissue, its cellular function in lung cancer remains largely unknown. Here, we report that the number of RBFOX3-positive cells in tumorous lung tissue is lower than that in normal lung tissue. As the transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway is important in cancer progression, we investigated its role in RBFOX3 expression in A549 lung adenocarcinoma cells. TGF-${\beta}1$ treatment inhibited RBFOX3 expression at the transcriptional level. Further, RBFOX3 depletion led to a change in the expression levels of a subset of proteins related to epithelial-mesenchymal transition (EMT), such as E-cadherin and Claudin-1, during TGF-${\beta}1$-induced EMT. In immunofluorescence microscopic analysis, mesenchymal morphology was more prominent in RBFOX3-depleted cells than in control cells. These findings show that TGF-${\beta}$-induced RBFOX3 inhibition plays an important role in EMT and propose a novel role for RBFOX3 in cancer progression.

Development of Transgenic Fish for the Production of Human EGF Protein (내재적 유전자에 의한 어류난자에서의 hEGE 단백질 생산을 위한 기술개발)

  • 황창남;송기철;이재현;윤종만;김기동;이상호;박홍양
    • Korean Journal of Animal Reproduction
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    • v.25 no.3
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    • pp.277-286
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    • 2001
  • Improvement and possible commercialization of a home-made electroporation apparatus(home-made) were further tried to establish a simple and effective introduction of foreign gene into sperm followed by in vitro fertilization. Expressions of introduced pJJ9 and pNT plasmids were shown in all fertilized eggs with electroporated spermatozoa. In particular, with this gene transfer system all the fry showed a consistently transient expression in the syncytium of the yolk sac. This fact is important since some required, minute quantity of human proteins can be produced from the established transient expression on the yolk sac of all fry derived from in vitro fertilization with electroporated spermatozoa. To explore tissue-specific expression in fish, which we will use a similar system later, we targeted the nerve tissue to see whether tissue-specific promoter is working in fish properly. pNT plasmid containing a nerve cell-specific tubulin promoter gene demonstrated consistently exact targeted expressions among the developing nerve cells in later stages of embryos and hatched fry. Finally, liver-specific genes are now being cloned by using already selected primers for useful human protein gene fusion.

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Dose Attenuation in the Mid-Cranial Fossa with 6 MV Photon Beam Irradiations (6 MV X-선 조사시 중두개와에서의 선량감쇠)

  • Park, Jeong-Ho;Choi, Tae-Jin;Kim, Ok-Bae
    • Radiation Oncology Journal
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    • v.8 no.1
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    • pp.125-131
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    • 1990
  • In X-ray irradiation, dose distribution depends on multiple parameters, one of them being tissue inhomogeneity to change the dose significantly. considerable dose attenuation through the mid-cranial fossa is expected because of various bony structures in it. Dose distribution around the mid-cranial fossa, following irradiation with 6 MV photon beam, was measured with LiF TLD micro-rod, and compared with the expected dose inthe same sites. In our calculation with $C_f$(correction factor), the expected dose attenuation revealed about $3.74\%$ per 1 cm thickness of bone tissue. And the differences between the expected dose with correction for bone tissue and the measured dose by TLD was small, agreeing within an average variation of $\pm0.21\%$.

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Prognostic Factors of Soft Tissue Sarcomas - analysis of 205 cases - (연부 육종의 예후 인자 - 205례 분석 -)

  • Lee, Jong-Seok;Jeon, Dae-Geun;Lee, Soo-Yong;Kim, Sug-Jun;Jung, Dong-Whan;Park, Hyun-Soo
    • The Journal of the Korean bone and joint tumor society
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    • v.3 no.2
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    • pp.89-97
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    • 1997
  • Twenty hundred and five out of 266 patients who were registered in Korea Cancer Center Hospital from Mar. 1985 to Jan. 1994, were analyzed in the aspect of survival and local recurrence. Fifty one patients were excluded due to inadequate data and follow up. Prognostic factors for survival were evaluated statistically. One hundred and four cases were male, 101 female. Average age was 39.7(range 1 to 77) year with a peak incidence around 4th decade. The most frequent diagnosis was malignant fibrous histiocytoma(MFH)(24.1%). Liposarcoma, synovial sarcoma, rhabdomyosarcoma, malignant peripheral nerve sheath tumor and fibrosarcoma were relatively common diagnostic entities, in decreasing order. In location, extremity was 179(87.3%) and trunk 26(12.7%). Average follow up period was 7.5 years(6 months to 10 years). Actuarial 5 years and 10 years survival rate were 64.0% and 40.8% respectively. In univariate analysis with log-lank test, significant differences in survival rate were noted in histopathological diagnosis, size(10 cm), stage and metastasis. Age, sex, tumor location, tumor depth and local recurrence didn't affect the survival rate. Adjuvant chemotherapy and/or radiotherapy did not affect overall survival rate, but lowered the local recurrence rate when compared with surgery only. Surgical margin did not affect the survival rate, but local recurrence rate was different according to each margin; 5.7% in more than wide; 39.5% in marginal; and 60.0% in intralesional excision. In multivariate analysis for results of univariate analysis with Cox's propotional model, metastasis was a meaningful factor for survival of soft tissue sarcoma.

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Controlled Release of Nerve Growth Factor from Sandwiched Poly(L-lactide-co-glycolide) Films for the Application in Neural Tissue Engineering

  • Gilson Khang;Jeon, Eun-Kyung;John M. Rhee;Lee, Ilwoo;Lee, Sang-Jin;Lee, Hai-Bang
    • Macromolecular Research
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    • v.11 no.5
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    • pp.334-340
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    • 2003
  • In order to fabricate new sustained delivery device of nerve growth factor (NGF), we developed NGF-loaded biodegradable poly(L-lactide-co-glycolide) (PLGA, the mole ratio of lactide to glycolide 75:25, molecular weight: 83,000 and 43,000 g/mole, respectively) film by novel and simple sandwich solvent casting method for the possibility of the application of neural tissue engineering. PLGA was copolymerized by direct condensation reaction and the molecular weight was controlled by reaction time. Released behavior of NGF from NGF-loaded films was characterized by enzyme linked immunosorbent assay (ELISA) and degradation characteristics were observed by scanning electron microscopy (SEM) and gel permeation chromatography (GPC). The bioactivity of released NGF was identified using a rat pheochromocytoma (PC-12) cell based bioassay. The release of NGF from the NGF-loaded PLGA films was prolonged over 35 days with zero-order rate of 0.5-0.8 ng NGF/day without initial burst and could be controlled by the variations of molecular weight and NGF loading amount. After 7 days NGF released in phosphate buffered saline and PC-12 cell cultured on the NGF-loaded PLGA film for 3 days. The released NGF stimulated neurite sprouting in cultured PC-12 cells, that is to say, the remained NGF in the NGF/PLGA film at 37 $^{\circ}C$ for 7 days was still bioactive. This study suggested that NGF-loaded PLGA sandwich film is released the desired period in delivery system and useful neuronal growth culture as nerve contact guidance tube for the application of neural tissue engineering.