• The Journal of Korean Physical Therapy
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• v.14 no.1
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• pp.131-137
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• 2002

C-fos는 원종양유전자(proto-oncogene)인 v-fos의 세포 동족체로써, 성장인자나 신경전달 물질에 의해 수분 내에 다양한 형태의 세포에서 활성화된다. Fos단백질은 스트레스와 통증 과정의 신호전달기전에서 세포활동을 조절하는 3차전령으로 활동한다. 열충격 단백질(Heat shock protein : 이하 HSP)은 계통발생학적으로 초기 척추 동물에서부터 발현되며 생체방어체계의 중요한 인자로 세포가 고열, 외상, 허혈 등의 스트레스에 직면했을 때 발현이 증가하는 단백질로 알려져 있다. 본 연구에서는 캡사이신(capsaicin)으로 말초 신경병변을 유발시킨 후 통각신경활성의 지표로 이용되는 원종양 유전자인 c-fos의 발현과 열 또는 스트레스로 야기되는 손상에 대한 조직의 방어작용으로 발현되는 HSP 70의 발현을 동시에 관찰함으로서, 급성으로 유발된 말초 신경병변의 확인과 동시에 실험동물 체내에서 방어적인 역할을 밝히는 일환으로 이 실험을 실시하였다. 본 실험의 결과는 다음과 같다; 1. 척수 등쪽뿔 천층(Laminae I and II)에서 각각 c-fos와 HSP70을 항원으로 하는 면역조직화학적 방법으로 염색한 표본에서 0.9% NaCI 투여 2시간 후 c-fos와 HSP70의 양성을 나타내는 세포는 전혀 없음을 알 수 있었다. 2. 척수 등쪽뿔 천층에서 c-fos 단백질을 항원으로 하는 면역조직화학적 방법으로 염색한 표본에서 Capsaicin 투여 2시간 후 c-fos 단백질에 양성을 나타내는 세포가 많이 발현됨을 육안적 관찰로서 알 수 있었다. 3. 척수 등쪽뿔 천층에서 HSP70을 항원으로 하는 면역조직화확적 방법으로 염색한 표본에서 Capsaicin 투여 2시간 후 HSP7O의 양성을 나타내는 세포가 보통수준으로 발현됨을 육안적 관찰로서 알 수 있었다. 이 실험의 결과로 볼 때, 화학적인 신경병변 유발물질에 의한 손상을 방어하기 위해서 체내에는 내인성 물질이 형성될 것이라는 추측과 c-fos 가 다른 유전자의 발현을 유도한다는 점을 함께 고려 하였을때, Capsaicin에 의한 말초 신경병변에서 c-fos 발현이 많이 나타나는 것은 손상을 방어하는 물질의 생성에 관여하기 때문이며, 방어물질 중 이 실험에서 본 HSP70도 증가한 내인성 방어물질의 하나라고 할 수 있을 것이다.

• Journal of Life Science
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• v.28 no.1
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• pp.116-129
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• 2018

Living creatures possess long-conserved mechanisms to maintain homeostasis in response to various stresses. However, chronic and continuous exposure to stress can result in the excessive production of stress hormones, including catecholamines, which have harmful effects on health. Studies on the relationship between the sympathetic nervous system (SNS) and cancer have been conducted based on the traditional hypothesis that stress can promote cancer progression. Many preclinical and epidemiological studies have suggested that the regulation of ${\beta}$-adrenergic signaling, which mediates SNS activity, can suppress the progression of solid tumors. SNS activation has highly pleiotropic effects on tumor biology, as it stimulates oncogenes, survival pathways, the epithelial - mesenchymal transition, and invasion. Moreover, it inhibits DNA repair and programmed cell death and regulates the tumor microenvironment, including immune cells, endothelial cells, the extracellular matrix, mesenchymal cells, and adipocytes. Although targeted therapies on the molecular basis of tumor proliferation are currently receiving increased attention, they have clinical limitations, such as the compensatory activation of other signaling pathways, emergence of drug resistance, and various side effects, which raise the need for pleiotropic cancer regulation. This review summarizes the effects of the SNS on the development and progression of cancer and discusses the clinical perspectives of ${\beta}$-blockade as a novel therapeutic strategy for this disease.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.306-313
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• 2023

Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β. Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.66-66
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• 2003

Protein tyrosine kinases는 표적단백질의 tyrosine 잔기를 인산화하는 효소로서 다양한 종류의 성장인자, peptide 호르몬, cytokine 수용체 하위의 세포 내 신호전달에 관여한다. Non-receptor tyrosine kinase의 일종인 c-Src는 세포막에서 발생한 ligand-receptor 상호작용 하위의 신호전달에서 중요한 역할을 하며 C-terminal Src kinase (Csk)는 Src kinase의 C-terminal tyrosine 잔기를 인산화시켜 Src kinase의 활성을 저해한다. 이러한 Src-Csk loop를 통한 세포 내 신호전달과정은 세포의 증식과 분화, 사멸 조절에 중요한 기능을 갖지만 정소의 발생과 분화 과정에서 Src-Csk loop의 발현 및 정자형성 과정에서의 기능은 밝혀지지 않았다. 본 연구에서는 생쥐 정소에서 출생 후 성적 성숙과정에서 Csk의 발현과 Src kinase 활성의 변동을 조사하였다. Csk mRNA 발현은 생 후 2주령 이하의 미성숙 정소에서 다량으로 발현되었고 사춘기 정소 이후에는 오히려 감소하였다. Csk 단백질의 발현 양상은 mRNA 발현양상과 일치하였다. c-Src kinase 활성은 생 후 2주에 급격히 증가하고 이 후 4주령에서 감소하다가 성체 (8주령)에서 다시 증가하여 가장 높았다. 성체 조직의 Csk 단백질 현존량이 미성숙 개체보다 적은 반면 Src kinase 활성은 가장 높아 Csk 발현의 감소는 Src kinase 활성을 증가하는 것으로 사료된다. 면역조직화학방법으로 정소 조직 내 Csk의 발현양상을 조사한 결과 Leydig cell, Sertoli cell, germ cell 등 도처에서 발현되었으며 Sertoli cell 에서의 발현은 세정관 상피의 구성에 따른 차이가 확인되었다. 성체의 세정관 내에서는 감수분열 이후의 정세포(spermatid)를 감싸고 있는 Sertoli cell의 강소측에서 강한 Csk 활성이 검출되어 생식세포의 분화과정 동안 세정관 상피의 조직재구성에 관여하는 것으로 사료된다. Leydig cell에서의 발현은 생후 1주령까지는 미미하였으나 이후 2주령 이후에는 다량으로 발현함이 확인되어 adult type Leydig cell에서 진행되는 steroidogenesis와의 관련성을 추측할 수 있다. 미성숙 정소로부터 분리한 Sertoli cell-enriched culture에 200 nM testosterone을 처리하였을 때 Csk mRNA의 발현의 증가를 확인할 수 있었으므로 androgen에 의한 Sertoli cell의 분화과정에 Csk가 관여하고 있음을 알 수 있다. 결론적으로 성적 성숙에 따른 생쥐 정소 내 Src-Csk loop의 발현과 Src kinase 활성의 변동은 정소 내 간충조직, 세정관 상피의 증식 및 기능적 분화 과정을 매개하는 생리적 활성분자 수용체 하위의 신호전달 과정에 Src-Csk loop에 의한 조절가능성을 확인할 수 있었다.

• Journal of Biomedical Engineering Research
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• v.15 no.1
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• pp.41-50
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• 1994

The chemotherapy using macromolecules, i.e., monoclonal antibodies loaded with anticancer agents hasn't been successful in delivering therapeutic amount of the conjugates. The comprehensive evaluation of mass transfer factors in tumor is prerequisite for the development of the effective chemotherapy. Characterization of neuroblastoma implanted in immunosuppressed athymic nude rats was performed. Its growth kinetics, glucose metabolic rate (GMR) were measured along with the interstitial fluid pressure (IFP), blood perfusion rate (BPR) and pH distribution throughtout the tumor radius. Volume doubling time and GMR were 8.1 days(SD 0.44 day), 23.53 mg/min/100 g(SD 3.54 mg/min/100 g), respectively. The IFP in tumor center was increased with tumor volume, and approached to 3 mmHg (SD 2.6 mmHg) when the tumor was 3 cm high. The radial distribution of IFP, BPR and pH in 2 cm high tumors showed that BPR and pH were decreased, while IFP was increased as the ~ensors moved toward the tumor center. The elevated IFP, decreased BPR and pH in tumor center suggested that the delivery of conjugates might be increased by properly manipulating mass transfer factors.

• The Korean Journal of Food And Nutrition
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• v.24 no.3
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• pp.273-281
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• 2011

Rice bran is byproducts of the hulling of rice, an important food resource in Korea. Various studies have been reported immune-enhancing effects of rice bran cultured with Lentinus edodes. In particular black rice bran contains anthocyanin, and the effects of antioxidant have been reported. The objective of the this study was to investigate the possible immune-enhancing effects of black rice bran substance extracted from a submerged culture of Lentinus edodes with black rice bran (crude fermentation-polysaccharide, CFP) and products(crude fermentation-polysaccharide-S. cerevisiae CFP-S, crude fermentation-polysaccharide-L. gasseri, CFP-L) which are of secondary fermentation of by using Saccharomyces cerevisiae and Lactobacillus gasseri in the Blab/c male mice. We found that supplementation of CFP, CFP-S and CFP-L enhanced macrophage and splenocyte proliferation compared to the control group(NC) in mice. Also, we measured the concentration of cytokines(IFN-${\gamma}$, TNF-${\alpha}$, IL-6) secreted by activated macrophage and splenocyte. The results of the experiment are that supplementation of CFP and CFP-S increased the macrophage and splenocyte proliferation compared to the control group but supplementation of CFP-L decreased the splenoyte proliferation compared to the control group(without mitogen and treated with LPS). When macrophage and splenocyte were stimulated by CFP and CFP-S supplementation, it was increased IFN-${\gamma}$, TNF-${\alpha}$ and IL-6 concentration compared with the control group. These results suggest that the capacity of CFP and CFP-S seem to act as a potent immune modulator causing augmentation of immune cell activity, and enhance the immue function through regulating cytokine production capacity by activated macrophage and splenocyte in mice.

• Clinical and Experimental Pediatrics
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• v.49 no.10
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• pp.1100-1105
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• 2006

Purpose : Because NELL2 expression is strictly restricted only in neurons in developing and post-differentiated neural tissues, it is thought to be involved in the neuronal differentiation during development and in the maintenance of neuronal physiology in the post-differentiated neurons. In this study, we examined whether NELL2 is involved in the regulation of cell cycle and apoptosis in the hippocampal neuroprogenitor HiB5 cells. Methods : Effects of NELL2 on the cultured HiB5 cell numbers, DNA fragmentation, and proteins involved in the regulation of the cell cycle were measured. Results : NELL2 induced a decrease in cell numbers and an increase in G1 phase arrest. Moreover, transfection of NELL2 resulted in an increase of DNA fragmentation that shows an evidence of apoptosis. Contents of proteins involved in the regulation of cell cycle were also changed by transfection of NELL2 expression vectors. Conclusion : This study suggests that NELL2 plays an important role in the regulation of cell cycle and apoptosis of neurons.

• Korean Journal of Food Science and Technology
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• v.40 no.3
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• pp.332-336
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• 2008

Ginger is widely used as a traditional herbal medicine. Both ginger and its extracts have been used to treat many chronic inflammatory conditions via the inhibition of nuclear factor-kappa B (NF-${\kappa}B$) activation, which results in the suppression of cyclooxygenase-2 (COX-2) expression. However, the mechanisms as to how ginger extracts mediate their health effects are largely unknown. Toll-like receptors (TLRs) trigger anti-microbial innate immune responses, recognizing conserved microbial structural molecules that are known as pathogen-associated molecular patterns. All TLR signaling pathways culminate in the activation of NF-${\kappa}B$. The activation of NF- ${\kappa}B$ leads to the induction of inflammatory gene products, including cytokines and COX-2. This study reports the biochemical evidence that 6-shogaol, an active compound in ginger, inhibits NF-${\kappa}B$ activation and COX-2 expression induced by TLR2, TLR3, and TLR4 agonists. Furthermore, 6-shogaol inhibited NF-${\kappa}B$ activation induced by the following downstream signaling components of the TLRs: MyD88, $IKK{\beta}$, and p65. These results imply that ginger can modulate immune responses that could potentially modify the risk of many chronic inflammatory diseases.

• Journal of Life Science
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• v.32 no.6
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• pp.476-481
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• 2022

Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.

• Journal of Life Science
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• v.15 no.6 s.73
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• pp.895-903
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• 2005

Thrombospondin-1 (TSP-1), a negative regulator in tumor growth and angiogenesis, is cell-type specifically regulated under pathological conditions or by extracellular stimuli, and the regulation of TSP-1 gene expression is important for developing new approaches in tumor therapy. Mistletoe is a parasitir plant that have been used for immunomodulation and antitumor therapy. Helixor A is an aqueous part of mistletoes extract. Here we showed that TSP-1 expression was significantly induced at both mRNA and protein levels in the Hepatocarcinorna cell line (Hep3B) and primary bovine endothelial cell line (BAE) exposed to Helixor A. Our promoter analysis confirmed that the expression of TSP-1 gene was regulated by Helixor A at the transcriptional level. In cell invasion assay, the conditioned media obtained from treatment of these cells significantly reduced the number of invasive cells and also inhibited capillary-like tube formation of BAE cells on Matrigel. Moreover, the inhibitory efforts of the conditioned media on cell invasion and tube formation were reversed by blocking with anti-TSP-1 neutralizing antibodies, suggesting that TSP-1 is involved in Helixor A-indured antiangiogenic effect. Taken together, our results suggest that Helixor A have an antiangiogenic effects through upregulation of TSP-1.