• 산업식품공학
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• 제21권1호
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• pp.1-11
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• 2017

Dyslipidemia, defined as elevated triglyceride (TG), total- and LDL-C, and/or decreased HDL-C levels, is considered a principal risk factor for cardiovascular disease. The low-density lipoprotein receptor (LDLR) family has been considered a key player in the prevention of dyslipidemia. The LDLR family consists of cytoplasmic membrane proteins and plays an important role not only in ligand-receptor binding and uptake, but also in various cell signaling pathways. Emerging reports state that various functional ingredients dynamically modulate the function of the LDLR family. For instance, oats stimulated the LDLR function in vivo, resulting in decreased body weight and improved serum lipid profiles. The stimulation of LRP6 by functional ingredients in vitro activated the Wnt/${\beta}-catenin$ pathway, subsequently suppressing the intracellular TG via inhibition of SREBP1, $PPAR{\gamma}$, and $C/EBP{\alpha}$. Furthermore, the extract of Cistanchetubulosa enhanced the expression of the mRNA of VLDLR, followed by a reduction in the serum cholesterol level. In addition, fermented soy milk diminished TG and total cholesterol levels while increasing HDL-C levels via activation of LRP1. To summarize, modulating the function of the LDLR family by diverse functional ingredients may be a potent therapeutic remedy for the treatment of dyslipidemia and cardiovascular diseases.

• International Journal of Stem Cells
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• 제17권3호
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• pp.298-308
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• 2024

Sine oculis homeobox 1 (Six1) is an important factor for embryonic development and carcinoma malignancy. However, the localization of Six1 varies due to protein size and cell types in different organs. In this study, we focus on the expression and localization of Six1 in male reproductive organ via bioinformatics analysis and immunofluorescent detection. The potential interacted proteins with Six1 were also predicted by protein-protein interactions (PPIs) and Enrichr analysis. Bioinformatic data from The Cancer Genome Atlas and Genotype-Tissue Expression project databases showed that SIX1 was highly expressed in normal human testis, but low expressed in the testicular germ cell tumor sample. Human Protein Atlas examination verified that SIX1 level was higher in normal than that in cancer samples. The sub-localization of SIX1 in different reproductive tissues varies but specifically in the cytoplasm and membrane in testicular cells. In mouse cells, single cell RNA-sequencing data analysis indicated that Six1 expression level was higher in mouse spermatogonial stem cells (mSSCs) and differentiating spermatogonial than in other somatic cells. Immunofluorescence staining showed the cytoplasmic localization of Six1 in mouse testis and mSSCs. Further PPIs and Enrichr examination showed the potential interaction of Six1 with bone morphogenetic protein 4 (Bmp4) and catenin Beta-1 (CtnnB1) and stem cell signal pathways. Cytoplasmic localization of Six1 in male testis and mSSCs was probably associated with stem cell related proteins Bmp4 and CtnnB1 for stem cell development.

• Asian-Australasian Journal of Animal Sciences
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• 제33권2호
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• pp.187-196
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• 2020

Objective: Porcine respiratory disease is one of the most important health problems causing significant economic losses. To understand the genetic basis for susceptibility to swine enzootic pneumonia (EP) in pigs, we detected 102,809 single nucleotide polymorphisms in a total of 249 individuals based on genome-wide sequencing data. Methods: Genome comparison of susceptibility to swine EP in three pig breeds (Jinhua, Erhualian, and Meishan) with two western lines that are considered more resistant (Duroc and Landrace) using cross-population extended haplotype homozygosity and F-statistic (F_ST) statistical approaches identified 691 positively selected genes. Based on quantitative trait loci, gene ontology terms and literature search, we selected 14 candidate genes that have convincible biological functions associated with swine EP or human asthma. Results: Most of these genes were tested by several methods including transcription analysis and candidate genes association study. Among these genes: cytochrome P450 1A1 and catenin beta 1 (CTNNB1) are involved in fertility; transforming growth factor beta receptor 3 plays a role in meat quality traits; Wnt family member 2, CTNNB1 and transcription factor 7 take part in adipogenesis and fat deposition simultaneously; plasminogen activator, urokinase receptor (completely linked to AXL receptor tyrosine kinase, r² = 1) plays an essential role in the successful ovulation of matured oocytes in pigs; colipase like 2 (strongly linked to SAM pointed domain containing ETS transcription factor, r² = 0.848) is involved in male fertility. Conclusion: These adverse genes susceptible to swine EP may be selected while selecting for economic traits (especially reproduction traits) due to pleiotropic and hitchhiking effect of linked genes. Our study provided a completely new point of view to understand the genetic basis for susceptibility or resistance to swine EP in pigs thereby, provides insight for designing sustainable breed selection programs. Finally, the candidate genes are crucial due to their potential roles in respiratory diseases in a large number of species, including human.

• IMMUNE NETWORK
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• 제4권1호
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• pp.23-30
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• 2004

Background: A human orthologue of mouse S100A6-binding protein (CacyBP), Siah-1-interacting protein (SIP) had been shown to be a component of novel ubiquitinylation pathway regulating $\beta$-catenin degradation. The role of the protein seems to be important in cell proliferation and cancer evolution but the expression pattern of SIP in actively dividing cancer tissues has not been known. For the elucidation of the role of SIP protein in carcinogenesis, it is essential to produce monoclonal antibodies specific to the protein. Methods: cDNA sequence coding for ORF region of human SIP gene was amplified and cloned into an expression vector to produce His-tag fusion protein. Recombinant SIP protein and monoclonal antibody to the protein were produced. The N-terminal specificity of anti-SIP monoclonal antibody was conformed by immunoblot analysis and enzyme linked immunosorbent assay (ELISA). To study the relation between SIP and colon carcinogenesis, the presence of SIP protein in colon carcinoma tissues was visualized by immunostaining using the monoclonal antibody produced in this study. Results: His-tag-SIP (NSIP) recombinant protein was produced and purified. A monoclonal antibody (Korea patent pending; #2003-45296) to the protein was produced and employed to analyze the expression pattern of SIP in colon carcinoma tissues. Conclusion: The data suggested that anti-SIP monoclonal antibody produced here was valuable for the diagnosis of colon carcinoma and elucidation of the mechanism of colon carcinogenesis.

• 동의생리병리학회지
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• 제17권6호
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• pp.1383-1392
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• 2003

Apoptosis is a morphologically and biochemically district form of cell death that occurs in many different cell types in a wide variety of organisms. Albizzia julibrissin belonging the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in oriental traditional medicine. This study investigates whether the water extract of A. julibrissin induce apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Jurkat cells were increased inhibitions of cell viability in a concentration-dependent manner by A. julibrissin. This herbal medicine also caused apoptosis as measured by cell morphology and DNA fragmentation. The capability of A. julibrissin to induce apoptosis was associated with proteolytic cleavage of specific target proteins such as poly (ADP-ribose)polymerase (PARP) and beta-catenin proteins suggesting the possible involvement of caspases. Our result showed that Bcl-2 and Bax protein levels were not changed in all A. julibrissin-treated groups compared to control group. These results suggest that A. julibrissin-mediated apoptosis is independent with Bcl-2 related signaling pathway in this cells. The purpose of the present study is also to investigate the Effect of A. julibrissin on cell cycle progression. Our results showed that G1 checkpoint related gene products (cyclin D1, cyclin dependent kinase 4, retinoblastoma, E2F1) were decreased in their protein levels in a dose-dependent manners after treatment of the extract. These results indicate that the increase of apoptotic cell death by A. julibrissin may be due to the inhibition of cell cycle progression in wild type p53-lacking Jurkat cells.

• Toxicological Research
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• 제28권1호
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• pp.39-49
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• 2012

We investigated the effect of zinc on the formation of colonic aberrant crypt foci induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in mice with high iron diet (HFe; 450 ppm iron). Sixweek old ICR mice were fed on high iron diets with combination of three different levels of zinc in diets, low-zinc (LZn; 0.01 ppm), medium-zinc (MZn; 0.1 ppm), and high-zinc (HZn; 1 ppm) for 12 weeks. Animals were received weekly intraperitoneal injections of AOM (10 mg/kg B.W. in saline) for 3 weeks followed by 2% DSS (molecular weight 36,000~50,000) in the drinking water for a week. To confirm the iron storage in the body, the hepatic iron concentration has been determine chemically and compared with histological assessment visualized by Prussian blue reaction. Aberrant crypt (AC) and aberrant crypt foci (ACF) were analyzed in the colonic mucosa of mouse fed high dietary iron. Superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) level were also investigated. Apoptosis in the preneoplastic lesion was determined by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL). In addition, immunohistochemistry of ${\beta}$-catenin was also performed on the mucous membrane of colon. The number of large ACF (${\geq}4$ AC/ACF), which possess greater tumorigenic potential, was significantly lower in MZn and HZn groups compared with LZn group. Cytosolic SOD activity in the liver was significantly higher in HZn group compared with LZn group. Hepatic MDA level was decreased significantly in HZn group compared with MZn and LZn groups. Apoptotic index was significantly higher in HZn group. Taken together, these findings indicate that dietary zinc might exert a protective effect against colonic preneoplastic lesion induced by AOM/DSS in ICR mice with high iron status, and suggest that dietary supplement of zinc might play a role in suppressing colon carcinogenesis in mice.

• 생명과학회지
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• 제17권8호통권88호
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• pp.1152-1156
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• 2007

본 실험은 동백꽃의 효능을 알아보기 위하여, 동백꽃을 에틸알콜로써 추출한 후 극성이 다른 다양한 유기용매로 분획하여 나온 fraction으로 신생혈관생성 억제, cell cytotoxity, 세포부착분자에 대한 기능을 ELISA, westen blot 등으로 조사하였다. 신생혈관생성 억제 효과는 특히butanol 층에서 70.2%로 가장 높았으며, acetone층이 54.2%, 그리고 ethylacetate층이 37.0%, chloroform층이 21.2%로 유의성 있는 억제효과가 있었다. 특히 동백꽃의 butanol층은 신생혈관생성억제제로서 좋은 효과가 있는 것으로 판단된다. 그리고, 추출물의 농도별로 cell cytotoxity를 조사한 결과 농도가 200 ug/ml 이하에서 세포독성은 나타나지 않았다. Cell adhesion 저해율은 추출물의 농도 200 μg/mL 에서 ICAM-1은 52.9%, VCAM-1은 62.5%, 그리고 E-selectin은 35.7%로 나타났으며 동백꽃의 추출물의 성분 증가에 따라 발현이 감소됨으로써 cell adhesion을 저해하는 것으로 확인되었다. Westen blot 에서 첨가한 동백꽃 추출물의 농도가 높아질수록 신호전달분자의 발현이 약해지는 것을 관찰할 수 있었다. 따라서 신호전달 분자는 동백꽃 추출물에 의해서 신호전달이 차단되며, NF-KB를 억제함으로서 신생혈관생성을 저해하는 것으로 확인되었다. 따라서 동백꽃 추출물은 항암제 및 항비만제제로서 유용할 것으로 판단된다.

• 생명과학회지
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• 제21권8호
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• pp.1109-1119
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• 2011

예로부터 한국, 일본 및 중국에서 민간처방 약재 및 건강식품으로 사용되어온 매실은 다양한 효능을 가지는 것으로 알려져 있으나 인체 암세포에서 유발하는 항암작용 및 그에 따른 분자생물학적 기작에 대해서는 명확히 밝혀져 있지 않다. 본 연구에서는 인체 혈구암 U937 세포에서 매실의 메탄올 추출물(MEPM)이 유발하는 항암효과 및 항암기전을 조사한 결과, MEPM 처리 농도 의존적으로 암세포의 성장억제 및 apoptosis를 유발하는 것으로 나타났다. MEPM에 의해서 유발되는 apoptosis에는 XIAP 및 survivin 등과 같은 IAP family의 발현 감소와 더불어 FasL의 발현 증가, Bcl-2의 발현 감소 및 Bid의 단편화 현상이 관여하는 것으로 나타났으며, 두 가지 apoptosis 유발 개시 및 최종 apoptosis 단계에서 중요한 역할을 하는 caspase-8과 -9 및 -3의 활성화와 그에 따른 다양한 기질단백질의 발현 감소 및 단편화가 동반되었음을 알 수 있었다. 또한 인위적인 caspase-3의 활성 차단으로 MEPM에 의하여 유발되는 apoptosis가 현저하게 억제되는 것으로 나타났다. 이상의 결과에서 MEPM은 암세포의 chemotherapeutic agent로서의 가능성을 확인하였지만 향후 지속적인 연구를 통하여 활성물질의 동정 및 관련 기전의 비교 등이 지속적으로 이루어져야 할 것으로 생각된다.

• 생명과학회지
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• 제18권6호
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• pp.804-813
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• 2008

본 연구에서는 전통 민간의학에서 많이 사용되는 동충하초(C. militaris)의 항암 작용에 관한 근거 자료의 제시를 위하여 동충하초 열수 추출물(WECM)의 항암 기전 해석을 시도하였다. 이를 위하여 HepG2 인체 간암세포를 사용하였으며, WECM의 처리에 의하여 HepG2 세포의 증식은 처리 농도의 증가에 따라 매우 억제되었다. WECM 처리에 의한 HepG2 세포의 증식 억제는 암세포의 심한 형태적 변형을 수반하였고, 이는 apoptosis 유도와 연관성이 있음을 DAPI 염색을 통한 apoptotic body 출현의 증가 및 flow cytometry 분석에 의한 sub-G1 기에 속하는 세포 빈도의 증가로 확인하였다. WECM 처리에 의한 HepG2 세포의 증식 억제는 또한 종양 억제 유전자 p53 및 CDKI p21의 발현 증가와도 연관성이 있음을 알 수 있었다. WECM 처리에 의한 apopotosis 유도에서 pro-apoptotic 인자인 Bax의 발현이 전사 및 번역 수준에서 매우 증가하였으며, caspase-3의 활성이 매우 높게 증가되었다. 특히 caspase-3 특이적 억제제인 z-DEVD-fmk로 caspase-3의 활성을 인위적으로 차단시켰을 경우, WECM에 의한 HepG2 세포의 apoptosis 유발에 caspase-3이 중심적인 역할을 하고 있음을 알 수 있었다. 본 연구 결과는 WECM의 생화학적 항암기전 해석을 이해하고 향후 수행될 추가 실험을 위한 기초 자료로서 그 가치가 매우 높은 것으로 생각된다.

• 대한한방내과학회지
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• 제28권3호
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• pp.473-491
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• 2007

Objectives : This study was designed to investigate the antiproliferative activity of the water extract of Samgibopae-tang (SGBPT) in NCI-H460 and A549 non-small-cell lung cancer cell lines Methods : In this study, we measured the subsistence, form of NCI-H460 and A549 non-small-cell lung cancer cell by hemocytometer and DAPI staining. In each cell, we analyzed DNA fragmentation. reverse transcription-polymerase chain reaction and measured activity of caspase-3, caspase-8 and caspase-9. Results and Conclusions : We found that exposure of A549 cells to SGBPT resulted in growth inhibition in a dose-dependent manner. butSGBPT did not affect the growth of NCI-H460 cells. The antiproliferative effect by SGBPT treatment in A549 cells was associated with morphological changes. SGBPT treatment partially induced the expression of DR5 cells and the expression of Faswas markedly increased in both transcriptional and translational levels in A549 cells. SGBPT treatment partially induced the expression of Bcl-2, Bcl-XL and the expression of Bid was markedly decreased in translational levels in A549 cells. However, SGBPT treatment did not affect the expression of IAP family in A549 orNCI-H460 cells. SGBPT treatment partially induced the expression of caspase-3, caspase-8, caspase-9 activity which markedly increased in a dose-dependent manners in A549 cells. The fragmental development of PARP and ${\beta}$-catenin protein was observed in A549 cells by SGBPT treatment. SGBPT treatment induced the expression of PLC-${\gamma}1$ protein which decreased in A549 cells. SGBPT treatment partially induced the expression of DFF45/ICAD which markedly increased in a dose-dependent manner in A549 cells. Taken together. these findings suggested that SGBPT-induced inhibition of human lung carcinoma did not affect NCI-H460 cell growth. However, SGBPT-induced inhibition of human lung carcinoma A549 cell growth was associated with the induction of death receptor and mitochondrial pathway. The results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of SGBPT.