• 한국자원식물학회지
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• 제26권6호
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• pp.673-677
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• 2013

In order to examine the effects of Korean cucurbitaceous plants on sonic hedgehog pathway and growth of cancer cells with over-activated hedgehog pathway, we measured the sonic hedgehog conditioned medium (shh-CM) induced alkaline phosphatase (ALP) activity and cell viability of pancreatic cancer cell lines by treatment of cucurbitaceous plants. Among the tested cucurbitaceous plants, Actinostemma lobatum Maxim, Cucumis sativus L., Momordica charantia L., Schizopepon bryoniaefolius Maxim and Trichosanthes kirilowii Max, var. japonica Kitam showed the potent inhibitory effects (> 50 % at $20{\mu}g/mL$) on shh-CM induced ALP activity. We also evaluated the cell viability of pancreatic cancer cells treated with the cucurbitaceous plants. The tested cucurbitaceous plants showed the very weak effects on cancer cell proliferation but, T. kirilowii Max, var. japonica Kitam presented the inhibitory effect of 72.7 % on the proliferation of pancreatic cancer cells at $20{\mu}g/mL$. Taken together, we screened the effects of Korean cucurbitaceous plants on shh-CM induced ALP activity and cell viability of pancreatic cancers to search for the modulators of the hedgehog pathway leading to the inhibition of cancer cell proliferation. T. kirilowii Max, var. japonica Kitam, among the tested cucurbitaceous plants, showed the inhibitory effects on the shh-CM induced ALP activity and the proliferation of pancreatic cancer cells.

• Natural Product Sciences
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• 제20권3호
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• pp.170-175
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• 2014

Twenty five methanolic plant extracts were investigated to determine the anticancer activity against sonic hedgehog (shh)/Gli signaling pathway dependent cancer, PANC-1 human pancreatic cancer cells, through three screening programs. All extracts were inspected their inhibitory properties on sonic hedgehog-conditioned medium (shh-CM) induced alkaline phosphatase (ALP) activity in C3H10T1/2 mouse mesenchymal stem cells to examine whether the plant extracts affect the shh/Gli signaling pathway. Next, plant extracts were screened the ability to suppress the cell proliferation of PANC-1 human pancreatic cancer cells. Finally, active plant extracts from the two screening systems were evaluated for the suppressive effect on Gli-mediated transcriptional activity in PANC-1 cells. Among active plants, Cinnamomum cassia suppressed Gli-mediated transcriptional activity leading to the down-regulated expression of Gli-target genes such as Gli-1 and Patched-1 (Ptch-1). This study provides the consideration for the important role of natural products in drug discovery process as well as the basis for the further analysis of active plant and potential identification of novel bioactive compounds as inhibitors of Gli and therapeutic candidates against shh/Gli signaling pathway dependent cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2319-2324
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• 2012

Aim: To investigate the expression of three components of the Hedgehog (Hh) signaling pathway (SHH, SMO and GLI1) in human colorectal cancer (CRC) tissues and evaluate their association with clinicopathologic characteristics of the patients. Methods: Fresh tumor tissues and matched tissues adjacent to the tumor were collected from 43 CRC patients undergoing surgery. Normal colorectal tissues from 20 non-CRC cases were also sampled as normal controls. The expression of SHH, SMO, GLI1 mRNAs was assessed by RT-PCR and proteins were detected by immunohistochemical staining. Associations with clinicopathological characteristics of patients were analyzed. Results: SHH mRNA was expressed more frequently in tumor tissues than in normal tissues, but the difference did not reach significance in comparison to that in the adjacent tissues. SMO and GLI1 mRNAs were expressed more frequently in tumor tissues than in both adjacent andnormal tissues. The expression intensities of SHH, SMO, GLI1 mRNA in tumor tissues were significantly higher than those in adjacent tissues and normal tissues. Proteins were also detected more frequently in tumors than other tissues. No significant links were apparent with gender, age, location, degree of infiltration or Dukes stage. Conclusion: Positive rates and intensities of mRNA and protein expression of Hh signaling pathway related genes SHH, SMO, GLI1 were found to be significantly increased in CRC tissues. However, over-expression did not appear to be associated with particular clinicopathological characteristics.

• Molecules and Cells
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• 제41권3호
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• pp.224-233
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• 2018

Primary cilia are solitary, non-motile, axonemal microtubule-based antenna-like organelles that project from the plasma membrane of most mammalian cells and are implicated in transducing hedgehog signals during development. It was recently proposed that aberrant SHH signaling may be implicated in the progression of idiopathic pulmonary fibrosis (IPF). However, the distribution and role of primary cilia in IPF remains unclear. Here, we clearly observed the primary cilia in alveolar epithelial cells, fibroblasts, and endothelial cells of human normal lung tissue. Then, we investigated the distribution of primary cilia in human IPF tissue samples using immunofluorescence. Tissues from six IPF cases showed an increase in the number of primary cilia in alveolar cells and fibroblasts. In addition, we observed an increase in ciliogenesis related genes such as IFT20 and IFT88 in IPF. Since major components of the SHH signaling pathway are known to be localized in primary cilia, we quantified the mRNA expression of the SHH signaling components using qRT-PCR in both IPF and control lung. mRNA levels of SHH, the coreceptor SMO, and the transcription factors GLI1 and GLI2 were upregulated in IPF compared with control. Furthermore, the nuclear localization of GLI1 was observed mainly in alveolar epithelia and fibroblasts. In addition, we showed that defective KIF3A-mediated ciliary loss in human type II alveolar epithelial cell lines leads to disruption of SHH signaling. These results indicate that a significant increase in the number of primary cilia in IPF contributes to the upregulation of SHH signals.

• 대한소아치과학회지
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• 제45권2호
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• pp.144-153
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• 2018

본 연구는 치근 및 치주조직의 형성과정동안 Sonic Hedgehog (SHH) signaling의 역할에 대해 알아보고자 치성간엽에서 조직특이적으로 Smoothened (Smo)가 활성화 또는 차단되는 mouse를 제작하여 분석하였다. 생후 28일경 Smo 활성화모델에서는 H-E 염색 시 얇은 두께의 치근상아질, 넓어진 치수강, 치주인대공간에 느슨하게 배열되어있는 섬유들이 관찰되었다. 면역조직화학염색 시 Smo 활성화모델은 wild type mouse와 비교하여 백악질, 치주인대 그리고/또는 백악모세포의 표식자인 Bsp, Dmp1, Periostin, Ank 같은 기질 단백질들의 발현이 현저히 감소하였다. 그러나 Smo 차단모델은 wild type mouse와 비교하여 이러한 기질 단백질들의 발현에 차이가 보이지 않았다. 본 연구를 통하여 치근 및 치주조직의 정상적인 형성과정에 낮은 수준으로 조절되는 SHH signaling이 필요하다는 것을 확인할 수 있었다.

• 한국동물생명공학회지
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• 제36권4호
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• pp.183-188
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• 2021

In vitro maturation (IVM) of oocytes is the procedure where the immature oocytes are cultivated in a laboratory until they are mature. Since IVM oocytes generally have low developmental competence as compared to those matured in vivo, development of an optimal IVM culture system by fine-tuning culture conditions is crucial to maintain high quality. In-depth knowledge and a deep understanding of the in vivo physiology of oocyte maturation are pre-requisites to accomplish this. Within ovarian follicles, various signaling pathways that drive oocyte development and maturation regulate interaction between oocytes and surrounding somatic cells. This review discusses the sonic hedgehog (SHH) signaling pathway, which has been demonstrated to be intimately involved in folliculogenesis and oocyte maturation. Advances in elucidating the role of the SHH signaling pathway in oocyte maturation will aid attempts to improve the current inferior in vitro oocyte maturation system.

• Advances in Computational Design
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• 제5권4호
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• pp.397-416
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• 2020

Functionally graded material (FGM) illustrates a novel class of composites that consists of a graded pattern of material composition. FGM is engineered to have a continuously varying spatial composition profile. Current work focused on buckling analysis of beam made of stepwise linear and quadratic graded material in axial direction subjected to axial span-load with piecewise function and rested on shear layer based on classical beam theory. The various boundary and natural conditions including simply supported (S-S), pinned - clamped (P-C), axial hinge - pinned (AH-P), axial hinge - clamped (AH-C), pinned - shear hinge (P-SHH), pinned - shear force released (P-SHR), axial hinge - shear force released (AH-SHR) and axial hinge - shear hinge (AH-SHH) are considered. To the best of the author's knowledge, buckling behavior of this kind of Euler-Bernoulli beams has not been studied yet. The equilibrium differential equation is derived by minimizing total potential energy via variational calculus and solved analytically. The boundary conditions, natural conditions and deformation continuity at concentrated load insertion point are expressed in matrix form and nontrivial solution is employed to calculate first buckling loads and corresponding mode shapes. By increasing truncation order, the relative error reduction and convergence of solution are observed. Fast convergence and good compatibility with various conditions are advantages of the proposed method. A MATLAB code is provided in appendix to employ the numerical procedure based on proposed method.

• 대한생식의학회:학술대회논문집
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• 대한생식의학회 2007년도 제53차 추계학술대회 초록집
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• pp.115.1-115.1
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• 2007

• The Journal of Korean Physical Therapy
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• 제13권2호
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• pp.433-444
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• 2001

This review highlights the ontogenesis and the differentiation of motor neuron in spinal cord, and introduce the survival motor neuron(SMN) which is associated with growth and survival of motor neurons. The differentiation of floor plate cells and motor neurons in the vertebrate neural tube appears to be induced by signals from the notochord. This signal is Sonic hedgehog(Shh). The early development of motor neurons involves the inductive action of Shh. The SMN gene is essential for embryonic viability. SMN mRNA is also expressed in virtually all cell types in spinal cord, including large motor neurons. The SMN protein is involved in RNA processing and during early embryonic development is necessary fer cell survival. Two SMN genes are present in 5q 13 in humans: the telomeric gene(SMNt), which is the SMA-determining gene, and the centromeric analog gene(SMNc). The majority of transcripts from the SMNt gene are full length but, major transcripts of the SMNc gene have a high degrees of alternative splicing and tend to have little or no exon 7. The SMN is involved in the RNA processing(the biogenesis of snRNPs and pre-mRNA splicing), the anti-apoptotic effects, and regulating gene expression.

• 한국측량학회지
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• 제16권1호
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• pp.1-7
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• 1998

SAR 영상은 기상이나 일조량에 관계없이 자료를 취득할 수 있으므로 종래의 전자광학적 감지기가 갖는 제약을 극복할 수 있다. 또한, SAR 영상으로 취득할 수 있는 정보는 종래의 광학적 감지기에 의한 것과는 다른 형태이므로 영상에 의한 정보취득의 범위를 확대시킬 수 있다. 그러나, SAR 영상에는 레이다의 특성과 대상물의 기하학적 특성에 따라 다양한 왜곡이 포함되므로, SAR 영상으로부터 정보를 취득하는 데 있어서 소요 정확도가 확보되기 위해서는 SAR 자료에 포함되어 있는 왜곡을 보정하여야 한다. 본 연구에서는 SAR 영상 취득시 대상물과 안테나의 기하학적 구성에 따른 반사파의 변화를 모형화하여 SAR 영상을 모의제작하고, 이를 이용해 대상물의 경사에 따른 밝기값의 왜곡을 실제 영상에서 제거하므로서 SAR 영상의 기하학적 복사 왜곡을 보정하고자 하였다. 그 결과, SAR 영상으로부터 대상물의 반사특성에 따른 정상적 정보를 취득함에 있어서 기하학적 복사왜곡에 의한 영향을 최소화하여 지형공간정보 관련 분야에서 SAR 영상을 원활히 활용할 수 있도록 기여하고자 하였다.