• BMB Reports
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• v.54 no.8
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• pp.419-424
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• 2021

Cold-induced norepinephrine activates β3-adrenergic receptors (β3-AR) to stimulate the kinase cascade and cAMP-response element-binding protein, leading to the induction of thermogenic gene expression including uncoupling protein 1 (Ucp1). Here, we showed that stimulation of the β3-AR by its agonists isoproterenol and CL316,243 in adipocytes increased the expression of Ucp1 and Heme Oxygenase 1 (Hmox1), the principal Nrf2 target gene, suggesting the functional interaction of Nrf2 with β3-AR signaling. The activation of Nrf2 by tert-butylhydroquinone and reactive oxygen species (ROS) production by glucose oxidase induced both Ucp1 and Hmox1 expression. The increased expression of Ucp1 and Hmox1 was significantly reduced in the presence of a Nrf2 chemical inhibitor or in Nrf2-deleted (knockout) adipocytes. Furthermore, Nrf2 directly activated the Ucp1 promoter, and this required DNA regions located at -3.7 and -2.0 kb of the transcription start site. The CL316,243-induced Ucp1 expression in adipocytes and oxygen consumption in obese mice were partly compromised in the absence of Nrf2 expression. These data provide additional insight into the role of Nrf2 in β3-AR-mediated Ucp1 expression and energy expenditure, further highlighting the utility of Nrf2-mediated thermogenic stimulation as a therapeutic approach to diet-induced obesity.

• BMB Reports
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• v.55 no.6
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• pp.287-292
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• 2022

The acute response to hypoxia is mainly driven by hypoxia-inducible factors, but their effects gradually subside with time. Hypoxia-specific histone modifications may be important for the stable maintenance of long-term adaptation to hypoxia. However, little is known about the molecular mechanisms underlying the dynamic alterations of histones under hypoxic conditions. We found that the phosphorylation of histone H3 at Ser-10 (H3S10) was noticeably attenuated after hypoxic challenge, which was mediated by the inhibition of aurora kinase B (AURKB). To understand the role of AURKB in epigenetic regulation, DNA microarray and transcription factor binding site analyses combined with proteomics analysis were performed. Under normoxia, phosphorylated AURKB, in concert with the repressor element-1 silencing transcription factor (REST), phosphorylates H3S10, which allows the AURKB-REST complex to access the MDM2 proto-oncogene. REST then acts as a transcriptional repressor of MDM2 and downregulates its expression. Under hypoxia, AURKB is dephosphorylated and the AURKB-REST complex fails to access MDM2, leading to the upregulation of its expression. In this study, we present a case of hypoxia-specific epigenetic regulation of the oxygen-sensitive AURKB signaling pathway. To better understand the cellular adaptation to hypoxia, it is worthwhile to further investigate the epigenetic regulation of genes under hypoxic conditions.

• BMB Reports
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• v.57 no.2
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• pp.92-97
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• 2024

Elevated blood glucose is associated with an increased risk of atherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosamine biosynthetic pathway (HBP), promoted lipid accumulation in RAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced by GlcN in RAW264.7 cells, although there was no a significant change in the rate of fatty acid uptake. GlcN increased acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory element-binding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) and ABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA binding activity. GlcN stimulated phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation in RAW264.7 cells. The GlcN-mediated increase in ACC and FAS mRNA was suppressed, while the decrease in ABCA-1 and ABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulation and further support a potential link between mTOR and HBP signaling in lipogenesis.

• Journal of Intelligence and Information Systems
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• v.16 no.3
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• pp.55-75
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• 2010

Sequential pattern mining aims to discover interesting sequential patterns in a sequence database, and it is one of the essential data mining tasks widely used in various application fields such as Web access pattern analysis, customer purchase pattern analysis, and DNA sequence analysis. In general sequential pattern mining, only the generation order of data element in a sequence is considered, so that it can easily find simple sequential patterns, but has a limit to find more interesting sequential patterns being widely used in real world applications. One of the essential research topics to compensate the limit is a topic of weighted sequential pattern mining. In weighted sequential pattern mining, not only the generation order of data element but also its weight is considered to get more interesting sequential patterns. In recent, data has been increasingly taking the form of continuous data streams rather than finite stored data sets in various application fields, the database research community has begun focusing its attention on processing over data streams. The data stream is a massive unbounded sequence of data elements continuously generated at a rapid rate. In data stream processing, each data element should be examined at most once to analyze the data stream, and the memory usage for data stream analysis should be restricted finitely although new data elements are continuously generated in a data stream. Moreover, newly generated data elements should be processed as fast as possible to produce the up-to-date analysis result of a data stream, so that it can be instantly utilized upon request. To satisfy these requirements, data stream processing sacrifices the correctness of its analysis result by allowing some error. Considering the changes in the form of data generated in real world application fields, many researches have been actively performed to find various kinds of knowledge embedded in data streams. They mainly focus on efficient mining of frequent itemsets and sequential patterns over data streams, which have been proven to be useful in conventional data mining for a finite data set. In addition, mining algorithms have also been proposed to efficiently reflect the changes of data streams over time into their mining results. However, they have been targeting on finding naively interesting patterns such as frequent patterns and simple sequential patterns, which are found intuitively, taking no interest in mining novel interesting patterns that express the characteristics of target data streams better. Therefore, it can be a valuable research topic in the field of mining data streams to define novel interesting patterns and develop a mining method finding the novel patterns, which will be effectively used to analyze recent data streams. This paper proposes a gap-based weighting approach for a sequential pattern and amining method of weighted sequential patterns over sequence data streams via the weighting approach. A gap-based weight of a sequential pattern can be computed from the gaps of data elements in the sequential pattern without any pre-defined weight information. That is, in the approach, the gaps of data elements in each sequential pattern as well as their generation orders are used to get the weight of the sequential pattern, therefore it can help to get more interesting and useful sequential patterns. Recently most of computer application fields generate data as a form of data streams rather than a finite data set. Considering the change of data, the proposed method is mainly focus on sequence data streams.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.9
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• pp.5675-5682
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• 2014

As oral diseases are developed by mixed infections, not by any single element, an accurate analysis of the causative microorganisms related to dental caries and periodontal diseases is required. In this study, saliva was collected from selected adults to determine if the bacteria that are well known as the causative microorganisms of dental caries and periodontal diseases would be detected in their saliva. In addition, this study examined whether there would be any differences among adults according to age, smoking, drinking and presence or absence of diseases in the distribution of oral bacteria to determine the risk factors for oral bacteria. The study subjects were 120 adults ranging in age from 20 to 65 years. The experiment data was collected from March 15, to May 2014. The gDNA was collected from the saliva, and the distribution of bacteria for oral diseases was investigated by PCR. The findings of the study were as follows. S. mutans was detected from 72 adults, and P. intermedia was detected from 88 adults. Both bacteria were detected from 54 adults, and no oral bacteria was detected in 14 adults. An analysis of the risk factors of oral bacteria showed that smokers had a 2.8-fold higher risk of S. mutans than nonsmokers, and the former had a 3.5-fold higher risk of P. intermedia than the latter. Drinkers had a 3.3-fold higher risk of S. mutans than nondrinkers. Patients who suffered from systemic diseases had a 4.1-fold higher risk of P. intermedia than those with no diseases. Therefore, smoking, drinking and systemic diseases are factors that increase the likelihood of oral bacteria detection. More periodontal disease bacteria were detected from older adults, and more oral bacteria were found in adults who were in their 20s, as dental caries and periodontal diseases were more common in this age group. The adults in which oral bacteria were detected are more likely to have dental caries or periodontal diseases, and they should try to keep their mouth cavity clean and make regular visits to a dental clinic to prevent possible oral diseases.

• Journal of Life Science
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• v.17 no.11
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• pp.1562-1570
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• 2007

This experiment was conducted to develop fertilizer which promotes plant growth as well as suppressing pathogenic fungi. The fertilizer was made from the mixture of Ju-Back (Korean rice wine cake) and indigenous rhizosphere-bacterium. The main ingredients of Ju-Back were investigated as 6.04% total nitrogen, 42.59% total carbohydrate, 1.01% available phosphate, 73.42% organic matter, 7.72% potassium oxide, 1.35% calcium oxide, 0.53% magnesium oxide. The enzyme activities of Ju-Back were estimated to be 980 units/g for ${\alpha}-amylase$, 300 units/g for glucoamylase, and 1800 units/g for acid pretense. Indigenous rhizosphere bacteria which produced antifungal agent were isolated from soil, and was selected KMU-13 strain which can antagonize against various plant pathogenic fungi (Botrytis cinerea KACC 40573, Sclerotinia sclerotiorum KACC 41065, Fusairum oxysporum KACC 40052, Pythium aphanidermatum KACC 40156, Phytophthora capsici KACC 40476 and Glomerella cingulata KACC 40299). KMU-13 strain was identified as Bacillus subtilis KMU-13 by biochemical and 16s rDNA analysis. The organic fertilizer was made as prototype which was composed 20% Ju-Back, 70% carrier, 9.7% microorganism cultivated solution, 0.3% trace-element. We also investigated an application of fertilizer using Ju-Back for cultivating lettuce (Lactuca sativar) which were grown in three soil conditions that had chemical fertilizer, barnyard manure, lime power, urea, potassium chloride and superphosphate as a control, the whole quantity (80 kg/10a) of posted fertilizer with the control and the half quantity (40 kg/10a) with the control. The growth characteristics were examined and analysed with several weeks interval from 3 weeks to 8 weeks on head length (cm), head width (cm/head), number of leaf and fresh weight (g/plant). The results are summarized as follows. The head width and fresh weight of lettuce were the highest at posted fertilizer 1 (whole quantity) was applied chemical, organic matter (Ju-Back) and carrier. The head length was the highest at posted fertilizer 2 (whole quantity) was applied Ju-Back only.

• The korean journal of orthodontics
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• v.24 no.1 s.44
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• pp.17-35
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• 1994

Vanadium is an essential trace element but has not been identified with a specific biogical role. To study the direct effects of vanadium on osteoblast, we incubated murin osteoblast-like (MC3T3-El) cells with various corcentration of vanadium oxide & sodium orthovanadate. This study was designed to investigate the effect of vanadium on DNA synthesis, alkaline phosphatase (ALP) activity, cAMP formation responsive to parathormone(PTH) and type I $\alpha$ 2 collagen ribonucleic acid (mRNA) level in murin osteoblast-like (MC3T3-El) cells. The cells were cultured in $\alpha-minimal$ essential medium$(\alpha-MEM)$ supplemented with $10\%$ fetal bovine serum (FBS) and then changed to $0.1\%$ FBS with various concenoation of vanadium oxide & sodium orthovanadate. Quiescent cultured MC3T3-El cells incubated for 24 hours with 2,5,10,15,20 ${\mu}M$ vanadium oxide incorporated $[^3H]Thymidine;$ every concentration showed increases in $[^3H]Thymidine$ incorporations dose dependant manner, the greatest response occurred at $20{\mu}M$. Quiescent cultured MC3T3-E1 cells incubated for 3days with 2,5,10,15,20 ${\mu}M$ vanadium oxide, for 2days with sodium orthovanadate and alkaline phosphatase was assayed with disodium phenyl phosphate as substrate. Vanadium oxide increased the alkaline phosphatase content in MC3T3-El cells at $2{\mu}M\;&\;6{\mu}M$ ; the greatest response occurred at $2{\mu}M$. But decreased at other content sodium orthovanadate increased alkaline phosphatase content in MC3T3-El cells at all concenoation ; the greatest response occurred at $4{\mu}M$. Quiescent cultured MC3T3-El cells incubated for 3days with $5,10{\mu}M$ vanadium oxide , with $5,8{\mu}M$ sodium orthovanadate and cAMP formation was measured by Radioimmunoassay(RIA). Vanadium oxide & sodium orthovanadate showed the tendency of inhibitory effects on cAMP responsiveness to PTH in MC3T3-El cells. Quiescent cultured MC3T3-El cells incubated for 24hours with $10,20{\mu}M$ vanadium oxide, with $5,10{\mu}M$ sodium orthovanadate and Type I $\alpha$ 2 collagen ribonucleic acid (mRNA) expression was studied by Nothern blot analysis. Northern blot analysis of vanadium oxide treated cells showed decreasing effects 0& sodium orthovanadate revealed increasing effects in type I $\alpha$ 2 collagen ribonucleic acid (mRNA) level.

• BMB Reports
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• v.42 no.4
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• pp.232-237
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• 2009

Sterol regulatory element-binding protein (SREBP)-1c plays a crucial role in the regulation of lipogenic enzymes in the liver. We previously reported that an X-chromosome-linked RNA binding motif (RBMX) regulates the promoter activity of Srebp-1c. However, still unknown was how it regulates the gene expression. To elucidate this mechanism, we screened the cDNA library from mouse liver by yeast two-hybrid assay using RBMX as bait and identified scaffold attachment factor B1 (SAFB1). Immunoprecipitation assay demonstrated binding of SAFB1 to RBMX. Chromatin immunoprecipitation assay showed binding of both SAFB1 and RBMX to the upstream region of Srebp-1c gene. RNA interference of Safb1 reduced the basal and RBMX-induced Srebp-1c promoter activities, resulting in reduced Srebp-1c gene expression. The effect of SAFB1 overexpression on Srebp-1c promoter was found only in the presence of RBMX. These results indicate a major role for SAFB1 in the activation of Srebp-1c through its interaction with RBMX.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2003.09a
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• pp.52-52
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• 2003

악성종양을 치료하는 방법중 방사선과 온열요법은 가장 강력한 치료방법으로 연구되어왔으며 이를 병용함으로 서 상승효과를 얻을 수 있다. 인체조직에 41$^{\circ}C$ 이상의 열을 가하면 세포질의 단백질변성으로 세포에 손상을 주어 세포가 사멸하게 되며 세포의 생존율은 가열시간 즉 열량에 따라 지수적으로 감소한다. 온열은 세포주기중 방사선 저항성이 매우 큰 DNA 합성시기와 산도가 높을 때 감수성이 매우 크기 때문에 방사선과 병용요법은 상호 상승효과를 가져온다. 이와 같이 온열을 이용한 악성종양의 치료가능성은 생물학적 기초연구와 임상시험에서 경이적인 효과를 얻을 수 있었으나 아직 까지 가열방법과 온도분포측정이 큰 과제로 남아있으며 주위건강조직의 가열을 피하면서 인체 깊은 곳에 존재하는 종양에만 집중 가열하는 방법인 삽입형 온열치료방법에 대한 연구가 집중되었다. 한편 방사선 치료방법은 주위 건강조직의 피폭을 최소로 줄이고 종양에만 집중 조사가 요구되며 자궁암, 유방암, 뇌암등 부피가 작고 집중적 치료를 요하는 종양은 방사성동위원소를 이용한 근접 삽입치료 (Brachyradiotherapy)가 큰 효과를 나타내고 있다 방사선과 온열의 병행 치료를 위하여 방사선 삽입 치료에 사용한 선원 삽입관을 그대로 두고 삽입관 속에 방사성 동위원소 대신 온열 전극을 넣어 열을 가하는 방사선 온열 병용치료방법을 고안하였으며 방사선과 온열병용에 사용할 최적 삽입관의 제작과 이에 따른 온도분포의 측정과 최적삽입방법을 결정하였다. 방사선 삽입치료용 폴리에찌렌 삽입관의 외부에 금박을 입혀 라디오파 첨극을 삽입할 때 서로 연결되도록 고안 제작함으로서 방사선 삽입치료와 자입식 온열치료를 동시에 만족하게 수행할 수 있는 병용삽입관 (Flexible thermoradiotherapy probes)을 제작하였다. 전도율이 큰 금박부위가 직접 조직에 접촉됨으로 라디오파의 전달이 용이하며 금박의 길이를 2 cm 에서 5 cm 로 구분제작 함으로서 종양의 크기와 모양에 따라 선택할 수 있도록 하였다. 라디오파를 이용한 온열분포의 측정은 인체조직과 전기적 특성이 비슷한 물질인 한천 팬텀 제작하여 사용하였으며 온도분포 측정은 열전대와 서머그람으로 시행하였다. 생체조직 내에서의 온도분포와 온열효과를 관찰하기 위하여 직접 개의 뇌를 이용하여 시행하였으며 4 개의 전극을 이용하여 43$^{\circ}C$로 50분간 가열하고 일주일후 개를 회생시켜 개 뇌에 대한 조직학적 검사를 시행하였다. 한편 팬텀 표면에서 중앙부로 안테나 길이가 2 cm 인 4 개의 전극을 1 cm 간격으로 정사각형이 되도록 삽입하여 가열하였을 때 90% 등온곡선이 반경 1.25의 원형으로 균일하게 분포되었고 종단면상 삽입관의 길이에 따라 균일한 온도분포가 이루어졌다. 전극을 2 cm 간격으로 삽일 하였을 때 90% 등온곡선이 1.75 반경으로 거의 4 각형의 균일한 분포를 얻었으나 전극의 간격이 증가하면 전도율이 떨어져서 전극 중심부에 불균일한 온도분포를 형성하였다. 동물실험에서 정상 개의 뇌 실질에 자입하여 직접 정방형의 중심을 43$^{\circ}C$로 유지하며 50분간 온열 요법을 시행한 후 관찰한 조직병리학적 소견은 liquefactive necrosis, pyknosis of neuronal element 및 polymorphonuclear leukocytes들의 회백질에서 급성기에 관찰되었고 liquefactive necrosis 주위에 lipid-laden macrophage들이 관찰됨이 공통적인 특정이었으며 후기변화로 괴사조직 주위로 신경교세포의 증식이 관찰되었다.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.67-75
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• 2015

Objectives : The aim of this study is to examine the neuroprotective effect of wheat bran extract (WBE) against ${\beta}$-amyloid ($A{\beta}$)-induced apoptotic cell death in SH-SY5Y human neuroblastoma cells and memory impairment in triple transgenic animal model's of Alzheimer's disease (3xTg AD mice). Methods : In SH-SY5Y cells, MTT assay and TUNEL staining were conducted to evaluate the protective effect of WBE against $A{\beta}_{25-35}$-induced neurotoxicity and apoptosis. Alterations in mitochondrial transmembrane potential (MMP), expression of proapoptotic Bax and antiapoptotic Bcl-2 proteins, cleavage of PARP, and brain-derived neurotrophic factor (BDNF) levels were analyzed to elucidate the neuroprotective mechanism of WBE. To further investigate the memory enhancing effect of WBE, Morris water maze test was performed in 3xTg AD mice. Results : In SH-SY5Y cells, WBE protected against $A{\beta}_{25-35}$-caused cytotoxicity and apoptosis as shown by the restoration of cell viability in MTT assay and inhibition of DNA fragmentation in TUNEL staining. $A{\beta}_{25-35}$-induced apoptotic signals such as dissipation of MMP, decreased Bcl-2/Bax ratio, and cleavage of PARP were suppressed by WBE. Moreover, WBE up-regulated the protein levels of BDNF, which seemed to be mediated by activation of cAMP response element-binding protein (CREB). In 3xTg AD mice, oral administration of WBE attenuated learning and memory deficit as verified by reduced mean escape latency in water maze test. Conclusions : WBE protects neuronal cells from $A{\beta}_{25-35}$-induced apoptotic cell death and restores learning and memory impairments in 3xTg AD mice. These findings suggest that WBE exhibit neuroprotective potential for the management of AD.