• 한국영양학회:학술대회논문집
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• 한국영양학회 2002년도 춘계학술대회
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• pp.29-41
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• 2002

While the sequencing of several genomes was underway, several advanced techniques in genetics, molecular biology and protein chemistry emerged. Within the nutritional sciences, while the focus on nutrition education, epidemiology and public health aspects remains essential; it is crucial to incorporate the new advances in gene and protein discovery in nutritional studies. Nutrition is a discipline that has always integrated social, biochemical and physiological sciences from the studies at the molecule level to studies at the population level. For this reason, nutritionists are in a prime position to readily incorporate the current genomics approaches in nutrition research, All the available analytical techniques can and should be used in modern nutritional sciences. These include genetics, genomics, proteomics and metabolomics which also require integration and use of bioinformatics and computational methods for data analysis and management. These applications will be briefly reviewed with a primary focus on what the genomics and genetics approaches offer to nutritionists. We will use one of our research focus areas to illustrate uses of some of these applications in obesity-hypertension research. Our central hypothesis is that adipose tissue is an endocrine organ that plays a major role in obesity and related hypertension. We are primarily studying the renin angiotensin system (RAS). We provide evidence from our own studies and others for the paracrine as well as endocrine role of adipocyte-derived angiotensin II in adipocyte gene expression, adiposity and blood pressure regulation. Both cell culture studies as well as knockout and transgenic mice models are used to test our hypothesis. Genomics and proteomics technologies are currently developed to complement our physiological and molecular studies on the RAS and for a fine analysis of this system and its function in health and disease.

• 한국영양학회:학술대회논문집
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• 한국영양학회 2002년도 춘계 심포지움초록
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• pp.598-603
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• 2002

While the sequencing of several genomes was underway, several advanced techniques in genetics, molecular biology and protein chemistry emerged. Within the notritional sciences, while the focus on nutrition education, epidemiology and public health aspects remains essential; it is crucial to incorporate the new advances in gene and protein discovery in nutritional studies. Nutrition is a discipline that has always integrated social, biochemical and physiological sciences from the studies at the molecule level to studies at the population level. for this reason, nutritionists are in a prime position to readily incorporate the current genomics approaches in nutrition research. All the available analytical techniques can and should be used in modem nutritional sciences. These include genetics, genomics, proteomics and metabolomics which also require integration and use of bioinformatics and computational methods for data analysis and management. These applications will be briefly reviewed with a primary focus on what the genomics and genetics approaches offer to nutritionists. We will use one of our research focus areas to illustrate uses of some of these applications in obesity-hypertension research. Our central hypothesis is that adipose tissue is an endocrine organ that plays a major role in obesity and related hypertension. We are primarily studying the renin angiotensin system (RAS). We provide evidence from our own studies and others for the paracrine as well as endocrine role of adipocyte-derived angiotensin II in adipocyte gene expression, adiposity and blood pressure regulation. Both cell culture studies as well as knockout and transgenic mice models are used to test our hypothesis. Genomics and proteomics technologies are currently developed to complement our physiological and molecular studies on the RAS and for a fine analysis of this system and its function in health and disease.

• IMMUNE NETWORK
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• 제7권4호
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• pp.186-196
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• 2007

Background: Although IL-12 has been widely accepted to playa central role in the control of pathogen infection, the use of recombinant IL-12 (rIL-12) as a vaccine adjuvant has been known to be ineffective because of its rapid clearance in the body. Methods: To investigate the effect of sustained release of IL-12 in vivo in the peptide and protein vaccination models, rIL-12 was encapsulated into poly ($A_{DL}$-lactic-co-glycolic acid) (PLGA). Results: We found that codelivery of IL-12-encapsulated microspheres (IL-12EM) could dramatically increase not only antibody responses, but also antigen-specific $CD4^+\;and\;CD8^+$ T cell responses. Enhanced immune responses were shown to be correlated with protective immunity against influenza and respiratory syncytial virus (RSV) virus challenge. Interestingly, the enhancement of $CD8^+$ T cell response was not detectable when $CD4^+$ T cell knockout mice were subjected to vaccination, indicating that the enhancement of the $CD8^+$ T cell response by IL-12EM is dependent on $CD4^+$ T cell "help". Conclusion: Thus, IL-12EM could be applied as an adjuvant of protein and peptide vaccines to enhance protective immunity against virus infection.

• BMB Reports
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• 제42권6호
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• pp.315-323
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• 2009

In order to elucidate ultimate biological function of the genome, the model animal system carrying mutations is indispensable. Recently, large-scale mutagenesis projects have been launched in various species. Especially, the mouse is considered to be an ideal model to human because it is a mammalian species accompanied with well-established genetic as well as embryonic technologies. In 1990', large-scale mouse mutagenesis projects firstly initiated with a potent chemical mutagen, N-ethyl-N-nitrosourea (ENU) by the phenotype-driven approach or forward genetics. The knockout mouse mutagenesis projects with trapping/conditional mutagenesis have then followed as Phase II since 2006 by the gene-driven approach or reverse genetics. Recently, the next-generation gene targeting system has also become available to the research community, which allows us to establish and analyze mutant mice carrying an allelic series of base substitutions in target genes as another reverse genetics. Overall trends in the large-scale mouse mutagenesis will be reviewed in this article particularly focusing on the new advancement of the next-generation gene targeting system. The drastic expansion of the mutant mouse resources altogether will enhance the systematic understanding of the life. The construction of the mutant mouse resources developed by the forward and reverse genetic mutagenesis is just the beginning of the annotation of mammalian genome. They provide basic infrastructure to understand the molecular mechanism of the gene and genome and will contribute to not only basic researches but also applied sciences such as human disease modelling, genomic medicine and personalized medicine.

• BMB Reports
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• 제41권6호
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• pp.415-434
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• 2008

Phosphoinositide-specific phospholipase C is an effector molecule in the signal transduction process. It generates two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. Currently, thirteen mammal PLC isozymes have been identified, and they are divided into six groups: PLC-$\beta$, -$\gamma$, -$\delta$, -$\varepsilon$, -$\zeta$ and -$\eta$. Sequence analysis studies demonstrated that each isozyme has more than one alternative splicing variant. PLC isozymes contain the X and Y domains that are responsible for catalytic activity. Several other domains including the PH domain, the C2 domain and EF hand motifs are involved in various biological functions of PLC isozymes as signaling proteins. The distribution of PLC isozymes is tissue and organ specific. Recent studies on isolated cells and knockout mice depleted of PLC isozymes have revealed their distinct phenotypes. Given the specificity in distribution and cellular localization, it is clear that each PLC isozyme bears a unique function in the modulation of physiological responses. In this review, we discuss the structural organization, enzymatic properties and molecular diversity of PLC splicing variants and study functional and physiological roles of each isozyme.

• Korean Journal of Acupuncture
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• 제24권2호
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• pp.129-139
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• 2007

목적 : Signal transducers and activators of transcription 6 (Stat 6) 유전자는 면역세포의 발달에 있어서 중요한 유전인자이며, IL-4와 같은 사이토카인에 의해 유전자 발현이 조절된다. 본 연구에서는 Stat 6 유전자 제거 생쥐와 정상 (wild type, W/T) 생쥐에 carrageenan으로 염증을 유도한 후 족삼리에 침치료를 시행하여 시상하부에서의 유전자 발현 양상을 분석하고자 하였다. 방 법 : BALB/c (W/T, n=12) and BALB/c-Stat 6 유전자 제거 생쥐 (n=12)의 발뒤꿈치 표피에 1% carrageenan을 30 ul 주사하여 염증을 유도하였다. 침은 염증 유도 30분 후에 족삼리(ST36)에 시침하였으며, 염증유도에 의한 부종 증가율을 매 시간마다 측정하여 총 5시간동안 측정하였다. 마이크로에러이는 Stat 6 유전자 제거 생쥐를 염증 유발 군과 염증유발 후 침을 처치한 군으로 나누고, 시상하부를 적출하여 RNA를 분리한뒤 마이크로어레이 프로파일을 분석하였다. 결 과 : 염증에 의한 부종증가율을 비교한 결과, Stat 6 유전자 제거 생쥐 그룹의 부종증가율이 W/T 생쥐의 부종 증가율보다 약 50 % 정도 감소하였으며, 각 3, 4, 5시간째에 유의한 차이를 나타내었다. (각 p<0.05). W.T생쥐군과 Stat 6 유전자 제거 생쥐군 모두에서, 침 처치군이 염증 유발 군에 비해, 염증 유발 2시간 후부터 유의한 감소를 나타내었다. 시상하부의 유전자 발현을 관찰한 결과, 39개의 유전자가 3배 이상 감소하였으며, 19개의 유전자는 3배 이상 증가하였다. 결 론 : W/T 생쥐군과 Stat 6 유전자 제거 생쥐 모두에서 침의 진통효과는 나타나며, 이의 기전에는 시상하부에서의 침 치료에 의한 염증관련 유전자들의 감소와, 항염증과 관련된 유전자들이 증가가 관여하는 것으로 보인다., 10, 11), 내측전완피신경(TE5, 6, 7, 8, 9, 10, 11), 후상완피신경(TE12, 13), 상외측상완피신경(TE13), 외측쇄골상신경(TE14, 15),대이개신경(TE16, 17, 18, 19), 소후두신경(TE19, 20), 이개측두신경(TE20, 21, 22), 안면신경측두지(TE22, 23), 관골측두신경(TE23), 중층에 견갑상신경(TE15), 견갑배신경(TE15), 경상설골근신경(TE17), 후이개신경(TE18, 19, 20), 안면신경측두지(TE20, 21, 22), 심층에 후골간신경(TE5, 6, 7), 요골신경심지(TE8, 9, 12, 13), 견갑상신경(TE14), 액와신경가지(TE14), 부신경(TE16), 안면신경과 부신경가지(TE17), 설인신경(TE17), 설하신경(TE17), 경신경고리(TE17), 미주신경(TE17), 안면신경 (TE18). 3) 혈(血) 관(管) : 천층에 척측정맥배측지(TE1, 2), 고유수장지동맥배측지(TE1), 배측중수골동맥배측지(TE2), 배측중수골정맥(TE3), 척측피정맥(TE4, 5, 6, 7, 8, 9, 10, 11), 배측정맥궁(TE4), 부요측피정맥(TE6, 8, 9),요측피정맥(TE10, 11), 후견봉정맥가지(TE13, 14), 후이개동 ${\cdot}$ 정맥(TE16, 17, 18, 19, 20), 전이개동 ${\cdot}$ 정맥(TE20), 천측두동 ${\cdot}$ 정맥(TE22, 23), 중층에 후상완회선동맥(TE14), 견갑배동맥(TE15), 견갑상동맥(TE15),천측두동 ${\cdot}$ 정맥(TE21), 관골측두동 ${\cdot}$ 정맥(TE23), 심층에 배측중수골동맥(TE3), 배측수근동맥궁(TE4), 후골간동맥(TE4, 5, 6, 7, 8, 9), 전골간동맥(TE6, 7, 9)

• 한국식품영양과학회지
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• 제43권3호
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• pp.333-340
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• 2014

본 연구는 한국 전통부각 제조방법을 이용하여 부각을 부식으로뿐만 아니라 스낵의 용도로도 사용할 수 있게 개발하고자 하였다. 부각 제조가 상대적으로 간편하며 원료 자체의 색상이 거의 없는 연근을 선정하여 여기에 빨강, 녹색 그리고 노란색을 낼 수 있도록 천연 기능성 색소 소재로 백년초, 녹차 그리고 치자 가루를 사용하였다. 이들 기능성 색소 재료를 삭힌 찹쌀풀 제조 후 첨가하여 다양한 부각을 만들고 이를 말린 후 생 참기름에 튀겨 동맥경화식이에 10%가 되도록 첨가하여 $LDLr^{-/-}$ 마우스에 10주간 섭취시켜 지질저하 기능성을 비교하였다. 실험군은 동맥경화유발식이를 섭취한 wild type mice 대조군(WC), $LDLr^{-/-}$ mice 대조군(CON), 그리고 동맥경화식이에 다양한 연근부각을 첨가한 연근부각군(LRB), 백년초연근부각군(OFB), 녹차연근부각군(GTB), 그리고 치자연근부각군(GFB)의 총 7군이었다. 부각의 효과를 비교하기 위하여 제한식이를 실시하였다. CON의 혈중 지질 농도는 WC에 비해 유의적으로 높았으며, LRB의 혈중 TG, TC 그리고 LDL-C 농도는 CON에 비해 유의적으로 낮았다(P<0.05). 기능성 색소 재료 첨가에 따른 지질저하 기능성을 살펴보았을 때 OFB와 GTB군의 혈중 TG, TC 그리고 LDL-C 농도가 LRB군에 비해 유의적으로 낮았다(P<0.05). 간의 지방산 합성 효소인 FAS와 콜레스테롤 합성 효소인 HMGCR의 발현 역시 OFB와 GTB군에서 LRB군에 비해 유의적 낮아(P<0.05) 혈중 지질 농도 결과와 일치하였다. 그러나 GFB군의 혈중 지질 농도는 LRB군보다 낮았으나 유의적인 차이를 보이지 않았고, FAS 및 HMGCR 발현 역시 유의적인 차이를 보이지 않았다. FAS 및 HMGCR의 mRNA 발현을 조절하는 전사인자인 SREBP-1과 2의 발현을 살펴보았을 때, OFB군과 GTB군은 LRB군에 비해 각각 유의적으로 낮았으나(P<0.05) GFB군에서는 발현 정도가 낮기는 하였으나 유의적이지 않았다. 이상의 결과로부터 백년초와 녹차 가루를 첨가하여 제조한 연근부각은 $LDLr^{-/-}$ 마우스의 간에서 지방산과 콜레스테롤의 생합성 억제를 통해 혈중 지질의 농도를 낮추는 효과가 있음을 확인하였다.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2008년도 International Meeting of the Microbiological Society of Korea
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• pp.23-25
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• 2008

Serum complement proteins comprise an important system that is responsible for several innate and adaptive immune defence mechanisms. There were three well described pathways known to lead to the generation of a C3 convertase, which catalyses the proteolysis of complement component C3, and leads to the formation of C3 opsonins (C3b, iC3b and C3d) that fix to bacteria. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial-binding C3 fragments recognized by leukocytes. The spleen clears microorganisms from the blood. Individuals lacking this organ are more susceptible to Streptococcus pneumoniae. Innate resistance to S. pneumoniae has previously been shown to involve complement components C3 and C4, however this resistance has only a partial requirement for mediators of these three pathways, such as immunoglobulin, factor B and mannose-binding lectin. Therefore it was likely that spleen and complement system provide resistance against blood-borne S. pneumoniae infection through unknown mechanism. To better understand the mechanisms involved, we studied Specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1. SIGN-R1, is a C-type lectin that is expressed at high levels by spleen marginal-zone macrophages and lymph-node macrophages. SIGN-R1 has previously been shown to be the main receptor for bacterial dextrans, as well as for the capsular pneumococcal polysaccharide (CPS) of S. pneumoniae. We examined the specific role of this receptor in the activation of complement. Using a monoclonal antibody that selectively downregulates SIGN-R1 expression in vivo, we show that in response to S. pneumoniae or CPS, SIGN-R1 mediates the immediate proteolysis of C3 and fixation of C3 opsonins to S. pneumoniae or to marginal-zone macrophages that had taken up CPS. These data indicate that SIGN-R1 is largely responsible for the rapid C3 convertase formation induced by S. pneumoniae in the spleen of mice. Also, we found that SIGN-R1 directly binds C1q and that C3 fixation by SIGN-R1 requires C1q and C4 but not factor B or immunoglobulin. Traditionally C3 convertase can be formed by the classical C1q- and immunoglobulin-dependent pathway, the alternative factor-B-dependent pathway and the soluble mannose-binding lectin pathway. Furthermore Conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-$R1^+$ spleen macrophages, and formation of C3 ligands. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway. We propose that in the SIGN-R1 mediated complement activation pathway, after binding to polysaccharide, SIGN-R1 captures C1q. SIGN-R1 can then, in association with several other complement proteins including C4, lead to the formation of a C3 convertase and fixation of C3. Therefore, this new pathway for C3 fixation by SIGN-R1, which is unusual as it is a classical C1q-dependent pathway that does not require immuno globulin, contributes to innate immune resistance to certain encapsulated microorganisms.

• Journal of Veterinary Science
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• 제23권1호
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• pp.8.1-8.15
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• 2022

Background: Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified. Objectives: To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles. Methods: Constructed Brucella abortus BspJ gene deletion strain (B. abortus ∆BspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro. Results: BspJ gene deletion reduced the survival and intracellular proliferation of Brucella at the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella. Conclusions: BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.

• Journal of Ginseng Research
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• 제44권6호
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• pp.815-822
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• 2020

Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. Methods: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. Results: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3⁺ regulatory T cells (Tregs) increased but IL-17-producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORgt expression and stimulating Foxp3 expression. Conclusion: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.