• Title/Summary/Keyword: GBA1

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GBA inhibition suppresses ovarian cancer growth, survival and receptor tyrosine kinase AXL-mediated signaling pathways

  • Gang Wang;Baisha Ouyang;Fang Jing;Xiaoyan Dai
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.21-29
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    • 2023
  • The poor outcome of advanced ovarian cancer under conventional therapy necessitates new strategies to improve therapeutic efficacy. β-glucosidase (encoded by GBA) is a lysosomal enzyme and is involved in sphingolipids metabolism. Recent studies revealed that β-glucosidase plays a role in cancer development and chemoresistance. In this work, we systematically evaluated the expression and role of GBA in ovarian cancer. Our work demonstrates that inhibition of β-glucosidase has therapeutic potential for ovarian cancer. Gene Expression Profiling Interactive Analysis database, western blot and immunohistochemistry analyses of patient samples demonstrated that GBA mRNA and protein expression levels were significantly increased in ovarian cancer compared to normal tissues. Functional studies using gainof-function and loss-of-function approaches demonstrated that GBA overexpression did not affect growth and migration but alleviated cisplatin's efficacy in ovarian cancer cells. In addition, GBA depletion resulted in growth inhibition, apoptosis induction, and enhancement of cisplatin's efficacy. Of note, we found that GBA inhibition specifically decreased receptor tyrosine kinase AXL level, leading to the suppression of AXL-mediated signaling pathways. Our data suggest that GBA represents a promising target to inhibit AXL signaling and overcome cisplatin resistance in ovarian cancer.

Effect of amaranth seed extracts on glycemic control in HepG2 cells (HepG2 세포에서 아마란스 종자 에탄올 추출물이 포도당 흡수 조절에 미치는 효과)

  • Park, So Jin;Park, Jong Kun;Hwang, Eunhee
    • Journal of Nutrition and Health
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    • v.54 no.6
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    • pp.603-617
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    • 2021
  • Purpose: This study was carried out to investigate the effect of amaranth seed extracts on glycemic regulation in HepG2 cells. The 80% ethanol extracts of amaranth seeds were used to evaluate α-amylase and α-glucosidase activities, cell viability, glucose uptake and messenger RNA (mRNA) expression levels of acetyl-CoA carboxylase (ACC), glucose transporter (GLUT)-2, GLUT-4, insulin receptor substrate (IRS)-1 and IRS-2. Methods: The samples were prepared and divided into 4 groups, including germinated black amaranth (GBA), black amaranth (BA), germinated yellow amaranth (GYA) and yellow amaranth (YA). Glucose hydrolytic enzyme, α-amylase and α-glucosidase activities were examined using a proper protocol. In addition, cell viability was measured by MTT assay. Glucose uptake in cells was measured using an assay kit. The mRNA expression levels of ACC, GLUT-2, GLUT-4, IRS-1 and IRS-2 were measured by reverse transcription polymerase chain reaction. Results: The inhibitory activities of α-amylase and α-glucosidase were highly observed in GBA, followed by BA, GYA and YA. Similar results were observed for glucose. The GBA effect was similar compared to the positive control group. The mRNA expression levels of ACC, GLUT-2, GLUT-4, IRS-1, and IRS-2 were significantly increased. The potential hypoglycemic effects of amaranth seed extracts were observed due to the increase in glucose metabolic enzyme activity, and glucose uptake was mediated through the upregulation of ACC, GLUT-2, GLUT-4, IRS-1, and IRS-2 expression levels. Conclusion: Our findings suggest that the amaranth seed is a potential candidate to prevent a diabetes. The present study demonstrated the possibility of using amaranth seeds, especially GBA and BA for glycemic control.

Soil stabilization by ground bottom ash and red mud

  • Kim, Youngsang;Dang, My Quoc;Do, Tan Manh;Lee, Joon Kyu
    • Geomechanics and Engineering
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    • v.16 no.1
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    • pp.105-112
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    • 2018
  • This paper presents results of a compressive investigation conducted on weathered soil stabilized with ground bottom ash (GBA) and red mud (RM). The effects of water/binder ratio, RM/GBA ratio, chemical activator (NaOH and $Na_2SiO_3$) and curing time on unconfined compressive strength of stabilized soils were examined. The results show that the water/binder ratio of 1.2 is optimum ratio at which the stabilized soils have the maximum compressive strength. For 28 days of curing, the compressive strength of soils stabilized with alkali-activated GBA and RM varies between 1.5 MPa and 4.1 MPa. The addition of GBA, RM and chemical activators enhanced strength development and the rate of strength improvement was more significant at the later age than at the early age. The potential environmental impacts of stabilized soils were also assessed. The chemical property changes of leachate from stabilized soils were analyzed in terms of pH and concentrations of hazardous elements. The observation revealed that the soil mixture with ground bottom ash and red mud proved environmentally safe.

The Micromorphometric change of the GBA and RBM implant surface conditioned with tetracycline-HCI (염산테트라싸이클린 적용시간에 따른 GBA 및 RBM 임프란트 표면변화)

  • Park, Kang-Hun;Herr, Yeek;Kwon, Young-Hyuk;Park, Joon-Bong;Chung, Jong-Hyuk
    • Journal of Periodontal and Implant Science
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    • v.36 no.3
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    • pp.705-716
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    • 2006
  • The present study was performed to evaluate the effect of tetracycline-HCl on the change of implant surface microstructure according to application time. Implant with pure titanium machined surface, GBA surface and RBM surface were utilized. Implant surface was rubbed with 50mg/ml tetracycline-HCl solution for ${\frac{1}{2}}$min. 1min. $1{\frac{1}{2}}$min. 2min. and $2{\frac{1}{2}}$min. respectively in the test group. Then, specimens were processed for scanning electron microscopic observation. The results of this study were as follow. 1. Both test and control group showed a few shallow grooves and ridges in pure titanium machined surface implants. There were not significant differences between two group. 2. In GBA surfaces, control group exhibit many porous depression, and each depression were divided by strict border. Experimental group applied with tetracycline-HCl for 2min. were similar with control group. But when applied for $2{\frac{1}{2}}$min. surface alteration and border breakdown started, resulting enlargement of the porous depression. 3. In REM surface, control group exhibit rough, uneven surface with crater-like depression can be found. The surface alteration started when tetracycline-HCl was applied for 30sec. resulting breakdown of the crater-like depression. Depression became larger as applying time increased.

N400 Event-related Potential and Gamma Band Activities during Visual Perception of Korean/English Words (한글 및 영어 단어의 시각적 인지 시 N400 사건관련 뇌전위 및 감마대역 활성화)

  • Yoon, Jin;Choi, Jung-Woo;Kim, Ja-Hyun;Kim, Kyung-Hwan
    • Journal of Biomedical Engineering Research
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    • v.29 no.6
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    • pp.477-483
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    • 2008
  • The observations of difference and similarity in brain activities involved in processing different languages have fundamental importance in cognitive neuroscience. The purpose of this study was to investigate the difference and similarity in temporal brain activation patterns due to the language difference during visual perception of Korean and English words under priming. Especially, we tried to find the difference in evoked spectral power in gamma-band, which is known to reflect feature binding. The stimulation was visually presented as word pairs belonging to same or different categories so that N400 event-related potential(ERP) was evoked. Average ERP analysis and spectral analysis of gamma-band activity(GBA) were performed on 12 normal Korean subjects. Several ERP components such as P1, N1, N400, and P600 could be identified consistently, and the differences in N1, N400, and P600 were observed. From the spectral analysis, we found that the evoked GBA(eGBA) was significantly larger for English at ${\sim}100$ ms poststimulus. The latency of the eGBA was also considerably delayed for English. Overall, the results on the ERP components and eGBA analyses seem to be commensurate with subjects' familiarity of each language, and the difficulty of perceiving words of each language. The methods of this study can also be applied for clinical purposes considering that the language-related processing can be greatly altered for the patients with neurological or psychiatric diseases.

A Review of Gaucher Disease in Korea

  • Sohn, Young Bae
    • Journal of mucopolysaccharidosis and rare diseases
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    • v.5 no.1
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    • pp.1-7
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    • 2021
  • Gaucher disease (GD, OMIM #230800 OMIM#230800) is a rare, autosomal recessive inherited metabolic disorder caused by mutation in GBA1 encoding the lysosomal enzyme, glucocerebrosidase. The deficiency of glucocerebrosidase leads to an accumulation of its substrate, glucosylceramide in macrophages of various tissues. Common clinical manifestations include cytopenia, splenomegaly, hepatomegaly, and bone lesions. The phenotype of GD is classified into three clinical categories: Type 1 (non-neuronopathic) is characterized by involvements on the viscera, whereas types 2 and 3 (neuronopathic) are associated with not only visceral symptoms but also neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 should be identified as they may be of prognostic value in some cases. Biomarkers including Chitotriosidase, CCL18, and glucosylsphingosine (lyso-GL1) are useful in diagnosis and treatment monitoring. Currently available disease-specific treatment in Korea consists of intravenous enzyme replacement therapy and substrate reduction therapy. For enhancing long-term prognosis, the onset of Parkinson's disease and Lewy body dementia, or the occurrence of a blood disease or cancer (hepatocellular carcinoma) should be monitored in older patients. The development of new strategies that can modify the neurological phenotype are expected, especially in Asia including Korea, where the prevalence of neuronopathic GD is relatively higher than that in western countries.

Chloride penetration resistance of concrete containing ground fly ash, bottom ash and rice husk ash

  • Inthata, Somchai;Cheerarot, Raungrut
    • Computers and Concrete
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    • v.13 no.1
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    • pp.17-30
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    • 2014
  • This research presents the effect of various ground pozzolanic materials in blended cement concrete on the strength and chloride penetration resistance. An experimental investigation dealing with concrete incorporating ground fly ash (GFA), ground bottom ash (GBA) and ground rice husk ash (GRHA). The concretes were mixed by replacing each pozzolan to Ordinary Portland cement at levels of 0%, 10%, 20% and 40% by weight of binder. Three different water to cement ratios (0.35, 0.48 and 0.62) were used and type F superplasticizer was added to keep the required slump. Compressive strength and chloride permeability were determined at the ages of 28, 60, and 90 days. Furthermore, using this experimental database, linear and nonlinear multiple regression techniques were developed to construct a mathematical model of chloride permeability in concretes. Experimental results indicated that the incorporation of GFA, GBA and GRHA as a partial cement replacement significantly improved compressive strength and chloride penetration resistance. The chloride penetration of blended concrete continuously decreases with an increase in pozzolan content up to 40% of cement replacement and yields the highest reduction in the chloride permeability. Compressive strength of concretes incorporating with these pozzolans was obviously higher than those of the control concretes at all ages. In addition, the nonlinear technique gives a higher degree of accuracy than the linear regression based on statistical parameters and provides fairly reasonable absolute fraction of variance ($R^2$) of 0.974 and 0.960 for the charge passed and chloride penetration depth, respectively.

Identification of Streptomyces sp. Producing Antibiotics Against Phytopathogenic Fungi, and Its Structure

  • Kim, Jung-Han;Jeong, Do-Hyeon;Park, Ki-Duk;Kim, Sung-Han;Kim, Kyung-Rae;Choi, Sung-Won;Kim, Ji-Tae;Choi, Ki-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.14 no.1
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    • pp.212-215
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    • 2004
  • In order to develop a biocontrol agent that can effectively control Fusarium wilt on Cymbidium genus, the effectiveness of antagonistic microbes against the cause pathogen was screened. The selected microbe showed a broad spectrum of antifungal activity, and the culture broth of this microbe had better preventive effect on Fusarium wilt than the commercial chemical agent in the pot assay. This isolated strain, GBA-12, was identified as Streptomyces kasugaensis, and the antifungal substance was purified from a broth culture of GBA-12. This purified substance was identified as a polyene macrolide (YS-822A) that was newly discovered from Streptomyces kasugaensis, and it exhibited antifungal activity against several phytopathogenic fungi.

Influence of Isoprene Emissions on Ozone Concentrations in the Greater Busan Area during a High Ozone Episode in 2006 (2006년 오존 고농도 사례 시 부산권 지역 isoprene 배출이 오존 농도에 미치는 영향 분석)

  • Kim, Yoo-Keun;Jo, Young-Soon;Song, Sang-Keun;Kang, Yoon-Hee;Oh, In-Bo
    • Journal of Environmental Science International
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    • v.19 no.7
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    • pp.829-841
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    • 2010
  • The estimation of a biogenic volatile organic compound (BVOC, especially isoprene) and the influence of isoprene emissions on ozone concentrations in the Greater Busan Area (GBA) were carried out based on a numerical modeling approach during a high ozone episode. The BVOC emissions were estimated using a biogenic emission information system (BEIS v3.14) with vegetation data provided by the forest geographical information system (FGIS), land use data provided by the environmental geographical information system (EGIS), and meteorological data simulated by the MM5. Ozone simulation was performed by two sets of simulation scenarios: (1) without (CASE1) and (2) with isoprene emissions (CASE2). The isoprene emission (82 ton $day^{-1}$) in the GBA was estimated to be the most dominant BVOC followed by methanol (56) and carbon monoxide (28). Largest impacts of isoprene emissions on the ozone concentrations (CASE2-CASE1) were predicted to be about 4 ppb in inland locations where a high isoprene was emitted and to be about 2 ppb in the downwind and/or convergence regions of wind due to both the photochemical reaction of ozone precursors (e.g., high isoprene emissions) and meteorological conditions (e.g., local transport).

Triple Folded Omnidirectional Microstrip Antenna for GBAS (GBAS용 3중 폴디드 무지향성 마이크로스트립 안테나)

  • Ju, Dae-Keun;Woo, Jong-Myung
    • The Journal of The Korea Institute of Intelligent Transport Systems
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    • v.20 no.4
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    • pp.83-94
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    • 2021
  • In this paper, we proposed a microstrip antenna (center frequency 118 MHz) with an omnidirectional radiation pattern that can replace the antennae used in VDB systems in GBAS. First, to obtain an omnidirectional radiation pattern from a microstrip antenna, we constructed a folded antenna. We then designed a miniaturized triple-folded antenna using perturbation effects. Thus we obtained suitable characteristics with a S11 of -13.91dB, -10 dB bandwidth of 1.5 MHz (1.27%) in the center frequency of 118 MHz. Furthermore, in the yz-plane and xy-plane, the component exhibits an omnidirectional radiation pattern, and the size of the antenna achieves miniaturization of 64.2% compared to the reference antenna. Finally, it is suitable as an antenna for VDB systems in GBAS.