• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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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.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.239-244
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• 2012

This study examined the inhibitory effects of 4-guanidinobutyric acid (4GBA), an alkaloid, against gastric lesions by assessing the inhibition of Helicobacter pylori (H. pylori) and gastric cancer cells. Acute and chronic gastritis were also observed using HCl/ethanol (EtOH) and indomethacin-induced gastric lesion models, respectively. 4GBA inhibited the growth of H. pylori in a dose dependent manner, and showed acid-neutralizing capacity. In the pylorus ligated rats, 4GBA decreased the volume of gastric secretion and gastric acid output slightly, and increased the pH. 4GBA at a dose of 100 mg/kg reduced the size of HCl/EtOH-induced gastric lesions (70.8%) and indomethacin-induced gastric lesions (38.8%). The antigastritic action of 4GBA might be associated with the acid-neutralizing capacity, anti-H. pylori action, and decreased volume of gastric secretion. These results suggest that 4GBA might be useful in the treatment and/or protection of gastritis.

• Journal of Nutrition and Health
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• 제54권6호
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• pp.603-617
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• 2021

혈당 조절에 유익한 천연 식품을 발굴하고 그 효과를 밝혀보고자 본 연구에서는 아마란스 종자에 주목하여 몇 가지 혈당조절 연관 지표의 증감 정도를 알아보았다. 아마란스 종자의 색과 발아 여부에 따라 효능에 차이가 있는지 알아보기 위하여 발아 흑색 아마란스는 germinated black amaranth (GBA), 비발아 흑색 아마란스는 black amaranth (BA), 발아 황색 아마란스는 germinated yellow amaranth (GYA), 비발아 황색 아마란스는 yellow amaranth (YA)로 구분하였고 각각의 시료는 80% 에탄올 추출물을 만들어 사용하였다. 본 연구에서 α-amylase 및 α-glucosidase 저해 활성을 측정한 결과 GBA, BA, GYA, YA 순으로 높은 저해 활성을 나타냈으며 특히 α-amylase 저해 활성 실험에서 GBA는 양성 대조물질인 acarbose와 거의 비슷한 수준을 나타내어 높은 저해 활성을 가지는 것으로 판단된다. HepG2 세포에서 포도당 흡수를 측정한 결과 모든 추출물에서 농도 의존적으로 증가하였고 GBA > BA > GYA > YA 순으로 높게 나타났다. 특히 50 ㎍/mL 농도에서 GBA는 인슐린과 유사한 값을 나타내었다. GBA를 농도별로 처리한 HepG2 세포에서 ACC, GLUT-2, GLUT-4, IRS-1, IRS-2 mRNA 발현 정도는 모두 농도 의존적으로 증가하였다. 이상의 결과로 아마란스 종자는 혈당 조절 및 개선에 효능이 있다고 평가되며 특히 발아한 흑색 종자가 혈당 조절 효능이 높게 나타남을 보여 혈당 조절에 유익한 효능을 가지는 식품 소재가 될 수 있음을 확인하였다.

• Molecules and Cells
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• 제38권9호
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• pp.806-813
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• 2015

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrowderived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

• Geomechanics and Engineering
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• 제16권1호
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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.

• 공업화학
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• 제33권4호
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• pp.440-443
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• 2022

만성 췌장염 치료제로 가장 널리 사용되고 있는 camostat mesylate 합성의 key step에 대한 연구를 수행하였다. Camostat mesylate는 두 중간체인 GBA (4-guanidinobenzoic acid hydrochloride)와 DOHA [2-(dimethylamino)-2-oxoethyl-2-(4-hydroxyphenyl)acetate]의 esterification 반응을 통해서 합성되는데, 기존의 esterification 방법 적용 시에는 낮은 수율과 고가의 시약으로 인한 문제점이 제기되어 왔다. 이런 문제점을 극복하고자 본 연구에서 Vilsmeier-Haack 반응을 이용하여 GBA의 acid 작용기를 activating하여 DOHA와 coupling하여 80%의 높은 수율로 Camostat mesylate를 제조할 수 있는 새로운 경제적인 합성법을 개발하였다.

• 대한의용생체공학회:의공학회지
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• 제29권6호
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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.

• Journal of Periodontal and Implant Science
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• 제36권3호
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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.

• 대한의용생체공학회:의공학회지
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• 제30권4호
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• pp.306-310
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• 2009

The purpose of this study is to observe the change in gamma-band cortical activities (GBAs) due to task difficulty. Event-related potential and gamma-band activity were investigated using electroencephalograms recorded during auditory oddball tasks with two difficulty levels. For more difficult task, the amplitude of P300 decreased and the peak latency of P300 was delayed significantly compared to easier task. The induced GBA decreased considerably during the P300 latency period and the peak latency of the induced GBA was delayed for more difficult task. The results imply that the difficulty-related change in cortical information processing may be implemented as a change in the strength of local neuronal association.

• 대한의용생체공학회:의공학회지
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• 제39권2호
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• pp.94-102
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• 2018

It is known that gamma-band activity (GBA) and phase synchrony (GBPS) are induced by emotional visual stimuli. However, the characteristics of GBA and GBPS according to different emotional states have not been identified. The purpose of this study is to investigate the changes in gamma-band neuronal synchronization induced by positive and negative emotional visual stimuli using electroencephalograms (EEGs). Thirteen healthy male subjects have participated in the experiment. The induced spectral power in gamma-band was the highest for negative stimuli, and the lowest for neutral stimuli in 300-2,000 ms after the stimulus onset. The inter-regional phase synchronization in gamma-band was increased in 500-2,000 ms, mainly between the bilateral frontal regions and the parieto-occipital regions. Larger number of significant connections were found by negative stimuli compared to positive ones. Judging from temporal and spatial characteristics of the gamma-band activity and phase synchrony increases, the results may imply that affective visual stimuli cause stronger memory encoding than non-emotional stimuli, and this effect is more significant for negative emotional stimuli than positive ones.