• BMB Reports
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• 제47권3호
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• pp.173-178
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• 2014

There is rapidly growing interest in the human microbiome because of its implication in metabolic disorders and inflammatory diseases. Consequently, understanding the biology of short chain fatty acids and their receptors has become very important for identifying novel therapeutic avenues. GPR41 and GPR43 have been recognized as the cognate receptors for SCFAs and their roles in metabolism and inflammation have drawn much attention in recent years. GPR43 is highly expressed on immune cells and has been suggested to play a role in inflammatory diseases such as inflammatory bowel disease. Both GPR41 and GPR43 have been implicated in diabetes and obesity via the regulation of adipose tissue and gastrointestinal hormones. So far, many studies have provided contradictory results, and therefore further research is required to validate these receptors as drug targets. We will also discuss the synthetic modulators of GPR41 and GPR43 that are critical to understanding the functions of these receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.1-10
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• 2024

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and dyslipidemia. Carvacrol (CAR) has demonstrated the potential to mitigate dyslipidemia. This study aims to investigate whether CAR can modulate blood glucose and lipid levels in a T2DM rat model by regulating short-chain fatty acids (SCFAs) and the GPR41/43 pathway. The T2DM rat model was induced by a high-fat diet combined with low-dose streptozocin injection and treated with oral CAR and/or mixed antibiotics. Fasting blood glucose, oral glucose tolerance, and insulin tolerance tests were assessed. Serum lipid parameters, hepatic and renal function indicators, tissue morphology, and SCFAs were measured. In vitro, high glucose (HG)-induced IEC-6 cells were treated with CAR, and optimal CAR concentration was determined. HG-induced IEC-6 cells were treated with SCFAs or/and GPR41/43 agonists. CAR significantly reduced blood lipid and glucose levels, improved tissue damage, and increased SCFA levels in feces and GPR41/43 expression in colonic tissues of T2DM rats. CAR also attenuated HG-induced apoptosis of IEC-6 cells and enhanced GPR41/43 expression. Overall, these findings suggest that CAR alleviates blood lipid and glucose abnormalities in T2DM rats by modulating SCFAs and the GPR41/43 pathway.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.48-54
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• 2022

GPR43 (also known as FFAR2), a metabolite-sensing G-protein-coupled receptor stimulated by short-chain fatty acid (SCFA) ligands is involved in innate immunity and metabolism. GPR43 couples with Gα_i/o and Gα_q/11 heterotrimeric proteins and is capable of decreasing cyclic AMP and inducing Ca²⁺ flux. The GPR43 receptor has additionally been shown to bind β-arrestin 2 and inhibit inflammatory pathways, such as NF-κB. However, GPR43 shares the same ligands as GPR41, including acetate, propionate, and butyrate, and determination of its precise functions in association with endogenous ligands, such as SCFAs alone, therefore remains a considerable challenge. In this study, we generated novel synthetic agonists that display allosteric modulatory effects on GPR43 and downregulate NF-κB activity. In particular, the potency of compound 187 was significantly superior to that of pre-existing compounds in vitro. However, in the colitis model in vivo, compound 110 induced more potent attenuation of inflammation. These novel allosteric agonists of GPR43 clearly display anti-inflammatory potential, supporting their clinical utility as therapeutic drugs.

• Asian-Australasian Journal of Animal Sciences
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• 제33권4호
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• pp.651-661
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• 2020

Objective: We hypothesized that Cr source can alter adipogenic-related transcriptional regulations and cell signaling. Therefore, the objective of the study was to evaluate the biological effects of chromium acetate (CrAc) on bovine intramuscular (IM) and subcutaneous (SC) adipose cells. Methods: Bovine preadipocytes isolated from two different adipose tissue depots; IM and SC were used to evaluate the effect of CrAc treatment during differentiation on adipogenic gene expression. Adipocytes were incubated with various doses of CrAc: 0 (differentiation media only, control), 0.1, 1, and 10 μM. Cells were harvested and then analyzed by real-time quantitative polymerase chain reaction in order to measure the quantity of adenosine monophosphate-activated protein kinase-α (AMPK-α), CCAAT enhancer binding protein-β (C/EBPβ), G protein-coupled receptor 41 (GPR41), GPR43, peroxisome proliferator-activated receptor-γ (PPARγ), and stearoyl CoA desaturase (SCD) mRNA relative to ribosomal protein subunit 9 (RPS9). The ratio of phosphorylated-AMPK (pAMPK) to AMPK was determined using a western blot technique in order to determine changing concentration. Results: The high dose (10 μM) of CrAc increased C/EBPβ, in both IM (p = 0.02) and SC (p = 0.02). Expression of PPARγ was upregulated by 10 μM of CrAc in IM but not in SC. Expression of SCD was also increased in both IM and SC with 10 μM of CrAc treatment. Addition of CrAc did not alter gene expression of glucose transporter 4, GPR41, or GPR43 in both IM and SC adipocytes. Addition of CrAc, resulted in a decreased pAMPKα to AMPKα ration (p<0.01) in IM. Conclusion: These data may indicate that Cr source may influence lipid filling in IM adipocytes via inhibitory action of AMPK phosphorylation and upregulating expression of adipogenic genes.

• 한국지하수토양환경학회지:지하수토양환경
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• 제21권4호
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• pp.30-41
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• 2016

The amount of groundwater related data is drastically increasing domestically from various sources since 2000. To justify the more expansive continuation of the data acquisition and to derive valuable implications from the data, continued employments of sophisticated and state-of-the-arts statistical tools in the analyses and predictions are important issue. In the present study, we employed a well established machine learning technique of Gaussian Process Regression (GPR) model in the trend analyses of groundwater level for the long-term change. The major benefit of GPR model is that the model provide not only the future predictions but also the associated uncertainty. In the study, the long-term predictions of groundwater level from the stations of National Groundwater Monitoring Network located within Han River Basin were exemplified as prediction cases based on the GPR model. In addition, a few types of groundwater change patterns were delineated (i.e., increasing, decreasing, and no trend) on the basis of the statistics acquired from GPR analyses. From the study, it was found that the majority of the monitoring stations has decreasing trend while small portion shows increasing or no trend. To further analyze the causes of the trend, the corresponding precipitation data were jointly analyzed by the same method (i.e., GPR). Based on the analyses, the major cause of decreasing trend of groundwater level is attributed to reduction of precipitation rate whereas a few of the stations show weak relationship between the pattern of groundwater level changes and precipitation.

• 한국지구물리탐사학회:학술대회논문집
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• 한국지구물리탐사학회 2008년도 공동학술대회
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• pp.41-46
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• 2008

국가하천을 대상으로 정밀외관조사에 의해 선정된20개 배수통문에 대하여 지표 물리탐사법외에 수리학적인 원리를 이용한 연통시험이나 초음파주사검층과 같은 공내시험법을 적용하여 배면의 공동상태를 보다 정확하게 파악하고자 하였다. 타음조사나 GPR 탐사, 3차원 전기비저항탐사 및 초음파주사검층은 일부 성공적인 결과를 얻을 수 있었으나 현장특성에 따라 적용이 용이하지 않은 경우가 발생하였다. 반면 연통시험의 경우에는 통문하부 공동의 유무 및 연통상태를 성공적으로 감지할 수 있었다. 그러나 연통시험은 공동의 규모나 형태에 대한 정량적인 정보를 제공하는데 근본적인 한계를 가지고 있으므로 보다 정확한 조사를 위해서는 현장특성에 맞는 다양한 조사법이 적용되어 종합적인 해석이 이루어야져야 할 것이다.

• 생명과학회지
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• 제22권11호
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• pp.1571-1586
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• 2012

지구상에는 약 5,400여 종의 포유동물이 있고 그 중 약 1,000여 종은 풀을 뜯어 먹고 사는 초식동물이다. 초식동물 중에서 약 250여 종이 반추동물로 알려져 있다. 반추동물인 소와 양은 반추위에서 주로 발효가 일어나지만 비반추동물인 돼지와 사람은 맹장과 결장, 직장에서 주로 발효가 일어난다. 반추위 미생물의 종류와 우점도 Bacteroidetes 51%, Firmicutes 43% 존재하며, 사람의 대장미생물의 우점도Firmicutes 65%, Bacteroidetes 25%로 존재한다. 풀의 세포벽 구성성분은 미생물에 의해 분해, 발효에 의해 SCFA (short chain fatty acid)를 생성하게 되고 acetate, propionate, butyrate 생성비율은 60:25:15이다. 장내 primary butyrate transporter인 MCT1(monocarboxylatetransports-1)에 의해서 흡수된 butyrate는 SCFA receptor GPR43과 GPR41을 활성화시킨다. Butyrate는 강력한 anti-tumorigenic 기능을 가지고 있다. Butyrate는 다양한 cancer cell에 효과를 나타내며 세포내의 기능 조절에 기여하고, 암세포사멸을 유도하는 특성이 있다. Butyrate는 caspase의 활성화, HDAC (histone deacetylase) 활성을 억제하여apoptosis를 유도하고, p53 발현증가로 cell cycle arrest와 apoptosis를 유도한다. SCFA의 항 염증작용으로는 장 상피세포에서 IL-8 발현 감소, NO합성과 NF-${\kappa}B$ (nuclear factor ${\kappa}B$)의 활성을 억제하여 염증으로 인한 암 발생을 억제한다. Butyrate는 장 점막의 생리적 기능을 유지하는데 중요한 역할을 하며 IBD (inflammatory bowel disease) 치료법으로 이용되고 있다.

• Toxicological Research
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• 제17권1호
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• pp.41-47
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• 2001

In order to test the effects of hyperbaric oxygen (HBO) and $\alpha$-tocopherol on full-thickness skin grafts in rats, we peeformed full-thickness skin grafts bilaterally on rats. After surgery, we analyzed the tissue-concentrations of superoxide dismutase (SOD), catalase, and glutathione peroxidase(GPx)/reductase(GPr) on days 0, 2, 4, 7, 10, 14, 21 and 28. The four groups had similar patterns of change in SOD, catalase, GPx and GPr values. SOD increased initially, and was significantly increased at day 7, returning to the preoperative activity level on day 14 (control, HBO, and $\alpha$-tocopherol treated alone) and 28 (HBO plus $\alpha$-tocopherol). Catalase had a similar pattern of change as the SOD enzyme activity, except for the surgical control on day 2. Glutathione peroxidase/reductase activity in the four groups had a similar pat-tern of enzyme activity, with a significant increase from preoperative level on day 4, peaking during days 7 to 10, and returning to preoperative level on day 21(surgical control, HBO, and $\alpha$-tocopherol-treated alone) and 28 (HBO plus $\alpha$-tocopherol treated group). Hence, the clinical use of HBO and $\alpha$-tocopherol mixture can be recommended as an adjunctive treatment for free skin grafts in rats. But, the antioxidant used, its dose, and the timing of its administration, as well as, the exposure time and the pressure of HBO, should be the subject of further research.

• 한국해양생명과학회지
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• 제1권1호
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• pp.41-49
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• 2016

Kisspeptin (Kiss) and its cognate receptor, kisspeptin receptor (KissR; G protein coupled receptor 54, GPR54), have recently been recognized as potent regulators of reproduction in teleosts. Additionally, leptin plays an important role in energy homeostasis and reproductive function in teleosts. The purpose of this study was to examine differences in the concentration of the hormones of the Kiss/KissR system and leptin and the expression of their underlying genes, all of which are involved in the sexual maturation of female goldfish, Carassius auratus, following treatment with Kiss. The expression levels of KissR increased after the Kiss injection. Furthermore, the peptide hormone leptin also increased after the injection (in vivo and in vitro). Additionally, the expression of GnRH and GTHs (GTHα, FSHβ, and LHβ) increased in the brain and pituitary (in vitro and in vitro). These results support the hypothesis that Kiss plays important roles in the direct regulation of the hypothalamus-pituitary-gonad axis and leptin in goldfish. Therefore, we suggest that Kiss system gene expression is correlated with energy balance and reproduction.

• 전자공학회논문지SC
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• 제41권5호
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• pp.9-18
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• 2004

본 논문에서는 펄스레이더를 이용한 차량검지 알고리즘을 제안하였다. 제안된 알고리즘은 likelihood개념을 이용한 likelihood ration를 통해 하나의 펄스신호에서 분류위치를 추출하고 추출된 분리점을 기준으로 신호를 분리, 간략화 하였다. 이렇게 처리 된 펄스신호에서 연속된 신호의 유클리드거리를 이용하여 단순 군집 탐색 알고리즘에 의해 차량을 검지하였고, 실험을 통해 제안된 알고리즘의 유용성을 확인하였다.