• Journal of the Korean Magnetic Resonance Society
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• v.24 no.4
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• pp.104-116
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• 2020

Fipronil, the phenylpyrazole insecticide, is effective and used in various fields. Especially, fipronil was reliable because it was known to be specific on invertebrate animals than vertebrate animals including mammals. However, fipronil had potential risks that affect vertebrate animals as it blocks the gamma-aminobutyric acid (GABA) receptors that also exists in vertebrates as well as invertebrates. Therefore, it was necessary that harmful effects of fipronil on vertebrates are clarified. For this purpose, the zebrafish (Danio rerio) were used on behalf of vertebrate animals in present study. The zebrafish were exposed to 5 ㎍/L, 25 ㎍/L, and 50 ㎍/L of fipronil during 12, 24 and 72 hours. To closely observe toxic process, 12 hours and 24 hours of additional time point were set in the exposure test. Nuclear magnetic resonance (NMR)-based metabolomics is an approach to detect metabolic changes in organism resulted from external stimuli. In this study, NMR-based metabolomics showed the metabolic changes in zebrafish caused by fipronil exposure. Metabolic analysis revealed that fipronil interfered with energy metabolism and decreased the antioxidant ability in zebrafish. Antioxidant ability decline was remarkable at high exposure concentration. In addition, metabolic analysis results over time suggested that reactions for alleviating the excessive nerve excitation occurred in zebrafish after fipronil exposure. Through this study, it was elucidated that the adverse effects of fipronil on vertebrate animals are evident. The risk of fipronil on vertebrates can be no longer ignored. Moreover, this study has a meaning of practically necessary research for organism by examining the effects of fipronil at low concentrations existed in real environment.

• Biomedical Science Letters
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• v.27 no.2
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• pp.69-76
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• 2021

The aim of this study was to evaluate gamma-aminobutyric acid (GABA)-induced erythropoietin (EPO) and EPO-receptor expression in human Hep3B cells and Sprague Dawley (SD) rats during hypoxia. Expression levels of EPO, EPO-R mRNA, Janus kinase-2 (JAK-2), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1), and HIF-2 in response to GABA treatment were evaluated in cell lines. SD rats were randomly divided into 5 groups of 8 rats each, and GABA was orally administered; the groups were the normal control (NC), hypoxia-exposed (G0), as well as the GABA 1 mg/100 g body weight (BW) GABA treated group (G1), 5 mg/100 g BW GABA treated group (G5), and 10 mg/100 g BW GABA treated group (G10) with hypoxia. We analyzed EPO levels and red blood cell counts in rat blood and EPO gene expression in kidney tissue. EPO and VEGF mRNA levels in Hep3B cells exposed to hypoxia were significantly increased and further increased after GABA treatment. However, the expression of EPO-R and JAK-2 mRNAs were not affected by GABA, but hypoxia-induced HIF-1 and HIF-2 mRNA expression was inhibited by GABA. In the kidney tissue of rats exposed to hypoxia, the expression level of EPO mRNA was greatly increased, but levels in the GABA treatment groups significantly decreased. EPO levels in the serum showed the same significant trend, but the red blood cell counts were not significantly different. These findings demonstrate that HIF-1 and HIF-2 activation increase EPO expression in Hep3B cells exposed to hypoxia. However HIF decreased by GABA addition and VEGF increased significantly.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.1
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• pp.50-60
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• 2021

Objective: This study investigated the mRNA expression of gamma-aminobutyric acid (GABA) receptors in the sperm of oligoasthenoteratozoospermic (OAT) and teratozoospermic (TER) men compared to normozoospermic (NOR) men, as well as the relationships between GABA receptor expression and sperm parameters, fertilization rate, and embryo quality. Methods: The mRNA expression of GABA A-α1 and GABA B-R2 receptors in sperm was examined using reverse transcription-polymerase chain reaction in three groups of patients: NOR (n=32), OAT (n=22), and TER (n=45). The fertilization rate and embryo quality were assessed in 35 patients undergoing intracytoplasmic sperm injection (ICSI; 10 NOR, 10 OAT, and 15 TER men). Results: OAT men had significantly higher mRNA expression of GABA A-α1 and GABA B-R2 receptors in sperm than NOR men; however, the difference between TER and NOR men was not significant. High levels of these receptors were significantly correlated with low sperm concentration, motility, and morphology, as well as the rate of good-quality embryos (GQEs) at the cleavage stage after ICSI. Patients whose female partners had a >50% GQE rate at the cleavage stage had significantly lower levels of GABA A-α1 receptor expression than those whose partners had a ≤50% GQE rate. Conclusion: Our findings indicate that mRNA levels of GABA receptors in human sperm are correlated with poor sperm quality and associated with embryo development after ICSI treatment. The GABA A-α1 receptor in sperm has a stronger relationship with embryo quality at the cleavage stage than the GABA B-R2 receptor.

• The Korean Journal of Pain
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• v.35 no.1
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• pp.43-58
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• 2022

Background: Current therapies are quite unsuccessful in the management of neuropathic pain. Therefore, considering the inhibitory characteristics of GABA mediators, the present systematic review and meta-analysis aimed to determine the efficacy of GABAergic neural precursor cells on neuropathic pain management. Methods: Search was conducted on Medline, Embase, Scopus, and Web of Science databases. A search strategy was designed based on the keywords related to GABAergic cells combined with neuropathic pain. The outcomes were allodynia and hyperalgesia. The results were reported as a pooled standardized mean difference (SMD) with a 95% confidence interval (95% CI). Results: Data of 13 studies were analyzed in the present meta-analysis. The results showed that administration of GABAergic cells improved allodynia (SMD = 1.79; 95% CI: 0.87, 271; P < 0.001) and hyperalgesia (SMD = 1.29; 95% CI: 0.26, 2.32; P = 0.019). Moreover, the analyses demonstrated that the efficacy of GABAergic cells in the management of allodynia and hyperalgesia is only observed in rats. Also, only genetically modified cells are effective in improving both of allodynia, and hyperalgesia. Conclusions: A moderate level of pre-clinical evidence showed that transplantation of genetically-modified GABAergic cells is effective in the management of neuropathic pain. However, it seems that the transplantation efficacy of these cells is only statistically significant in improving pain symptoms in rats. Hence, caution should be exercised regarding the generalizability and the translation of the findings from rats and mice studies to large animal studies and clinical trials.

• Clinical and Experimental Pediatrics
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• v.65 no.4
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• pp.172-181
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• 2022

Pubertal onset is known to result from reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, which is controlled by complex interactions of genetic and nongenetic factors. Most cases of precocious puberty (PP) are diagnosed as central PP (CPP), defined as premature activation of the HPG axis. The cause of CPP in most girls is not identifiable and, thus, referred to as idiopathic CPP (ICPP), whereas boys are more likely to have an organic lesion in the brain. ICPP has a genetic background, as supported by studies showing that maternal age at menarche is associated with pubertal timing in their offspring. A gain of expression in the kisspeptin gene (KISS1), gain-of-function mutation in the kisspeptin receptor gene (KISS1R), loss-of-function mutation in makorin ring finger protein 3 (MKRN3), and loss-of-function mutations in the delta-like homolog 1 gene (DLK1) have been associated with ICPP. Other genes, such as gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), lin-28 homolog B (LIN28B), neuropeptide Y (NPYR), tachykinin 3 (TAC3), and tachykinin receptor 3 (TACR3), have been implicated in the progression of ICPP, although their relationships require elucidation. Environmental and socioeconomic factors may also be correlated with ICPP. In the progression of CPP, epigenetic factors such as DNA methylation, histone posttranslational modifications, and non-coding ribonucleic acids may mediate the relationship between genetic and environmental factors. CPP is correlated with short- and long-term adverse health outcomes, which forms the rationale for research focusing on understanding its genetic and nongenetic factors.

• The Korean Journal of Pain
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• v.36 no.4
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• pp.425-440
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• 2023

Background: Muscimol's quick onset and GABAergic properties make it a promising candidate for the treatment of pain. This systematic review and meta-analysis of preclinical studies aimed at summarizing the evidence regarding the efficacy of muscimol administration in the amelioration of nerve injury-related neuropathic pain. Methods: Two independent researchers performed the screening process in Medline, Embase, Scopus and Web of Science extracting data were extracted into a checklist designed according to the PRISMA guideline. A standardized mean difference (SMD [95% confidence interval]) was calculated for each. To assess the heterogeneity between studies, ² and chi-square tests were utilized. In the case of heterogeneity, meta-regression and subgroup analyses were performed to identify the potential source. Results: Twenty-two articles met the inclusion criteria. Pooled data analysis showed that the administration of muscimol during the peak effect causes a significant reduction in mechanical allodynia (SMD = 1.78 [1.45-2.11]; P < 0.0001; I² = 72.70%), mechanical hyperalgesia (SMD = 1.62 [1.28-1.96]; P < 0.0001; I² = 40.66%), and thermal hyperalgesia (SMD = 2.59 [1.79-3.39]; P < 0.0001; I² = 80.33%). This significant amendment of pain was observed at a declining rate from 15 minutes to at least 180 minutes post-treatment in mechanical allodynia and mechanical hyperalgesia, and up to 30 minutes in thermal hyperalgesia (P < 0 .0001). Conclusions: Muscimol is effective in the amelioration of mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia, exerting its analgesic effects 15 minutes after administration for up to at least 3 hours.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.8
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• pp.1012-1017
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• 2017

Mesembryanthemum crystallinum (Family: Aizoaceae) is an annual plant consisting of ice crystal-shaped bladder cells, which is responsible for its common name ice plant. This study investigated biological activities according to general components and extraction solvent in order to examine the functionality of ice plant. The total content of free amino acids was 32.57 mg/g, including 4.64 mg/g of L-alanine as the most abundant and 2.60 mg/g of ${\gamma}$-aminobutyric acid. Regarding angiotensin converting enzyme inhibitory activities of solvent fractions of ice plant, ethyl acetate fraction and chloroform fraction showed activities of $33.17{\pm}3.20{\sim}88.19{\pm}3.20%$ and $23.72{\pm}2.89{\sim}86.78{\pm}2.24%$, respectively, similar to $Captopril^{(R)}$ ($19.51{\pm}3.44{\sim}84.72{\pm}1.06%$) and $Enalapril^{(R)}$ ($24.93{\pm}1.12{\sim}91.32{\pm}3.62%$) as positive control groups. Regarding inhibition of lipid droplet production in 3T3-L1 preadipocytes by ice plant, anti-adipogenic activities were $53.00{\pm}0.45{\sim}65.75{\pm}0.31%$ and $44.16{\pm}0.29{\sim}63.32{\pm}0.36%$ in the ethyl acetate fraction and butanol fraction, respectively, showing the lowest lipid droplet production. The chloroform fraction and hexane fraction showed activities of $38.33{\pm}0.09{\sim}56.55{\pm}0.50%$ and $31.17{\pm}0.50{\sim}55.10{\pm}1.93%$, respectively, whereas the water fraction showed activity of $26.32{\pm}2.27{\sim}49.48{\pm}0.05%$. Therefore, all solvent fractions inhibited fat accumulation of 3T3-L1 preadipocytes according to treatment concentration. According to the results above, it would be possible to utilize ice plant as a new health functional material.

• Journal of The Korean Society of Grassland and Forage Science
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• v.29 no.3
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• pp.263-268
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• 2009

This study was conducted to determine application possibility of mulberry (Morus alba) silage as a functional feed in feeding management of Korean native cattle for high quality beef production by analysing active components and antioxidative activity. The chemical analysis of mulberry silage indicates that the content of dry matter, crude protein, ether extract, crude fiber and crude ash was $28.41{\pm}3.12%,\;12.43{\pm}0.28%,\;2.47{\pm}0.18%,\;20.29{\pm}0.75%\;and\;6.98{\pm}0.12%$, respectively. The content of 1-deoxynojirimycin (1-DNJ), which is representative active ingredient of mulberry and blood sugar descending component, was 0.568 mg/g and the content of $\gamma$-Aminobutyric acid (GABA), which is blood pressure descending component, was 5,936.22 pmol. Mulberry silage used in this study did not contain flavonoids but did contain total phenols for 21.69 ${\mu}g/mg$. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity was increased with increasing the concentration of mulberry silage extracts and there was above 50% of scavenging activity at the concentration of 0.25 mg/ml. Hydroxyl radical scavenging activity was also increased with increasing the concentration of silage extracts. Alkyl radical scavenging activity was high at the low concentration of silage extracts, which was above 50% of scavenging activity at the concentration of 0.125 mg/ml. The result of this study indicated that there was high possibility of mulberry silage as a functional feed for beef cattle.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.10
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• pp.1395-1401
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• 2012

This study investigated the cognition-related effects on antioxidant activities, ${\gamma}$-aminobutyric acid (GABA) contents, and AChE inhibitory activities in ethanol extracts from Zingiber officinale Rosc. (Korea), Curcuma longa L. (Korea), Curcuma longa L. (Myanmar), and Curcuma aromatica Salisb. (India). These extracts were investigated to determine the relationships among total polyphenols as well as DPPH and ABTS radical scavenging activities, GABA contents, and acetylcholinestrase (AChE) inhibitory activity. For the results, C. longa L. from Myanmar exhibited the highest contents of curcumin (97.1 ${\mu}g/mg$), total polyphenols (98.4 ${\mu}g/mg$), and GABA (1.31 ${\mu}g/mg$), as well as the strongest radical scavenging activities and AChE inhibitory activity. In addition, C. aromatica Salisb from India, which had the highest total polyphenol content (98.4 ${\mu}g/mg$) and strongest radical scavenging activities, exhibited relatively high AChE inhibitory activity similar to that of C. longa L. from Myanmar. On the other hand, Z. officinale Rosc. and C. longa L. from Korea showed low contents of curcumin (12.2 ${\mu}g/mg$) and polyphenols (85.7 ${\mu}g/mg$), as well as low AChE inhibitory activities. However, we could detect 1.11 ${\mu}g/mg$ of GABA in these extracts, which was similar to that of C. longa L. from Myanmar. Therefore, GABA content was not correlated with AChE inhibitory activity. Based on the results, AChE inhibitory activity is highly correlated with polyphenol contents in Zingibearceae family. Overall, among the Zingiberaceae tested, C. longa L. from Myanmar might be a strong candidate as a cognitive-enhancing ingredient.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.51 no.spc1
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• pp.133-138
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• 2006

To differentiate barley responses to drought and salt stress, barley seedlings at the second leaf stage were treated with 218 mM NaCl and 29.5% PEG6000 iso-osmotic to 218 mM NaCl for 6 days. Shoot fresh weight and leaf relative water content of barley seedlings were more reduced by drought compared to salt stress. Hydrogen peroxide content increased under both stress conditions, but its accumulation was more severe at 6 days after salt stress. The activity of ascorbate peroxidase, glutathione reductase (GR) and catalase (CAT) was enhanced until 4 days after salt stress. On the other hand, the activity of GR and CAT increased gradually until 6 days after drought. Among the amino acids measured in this study, the accumulation of glycine, arginine and GABA (${\gamma}-aminobutyric$ acid) was lower under salt stress than drought. However, considerably larger amount of proline was accumulated by salt stress. It is concluded that the antioxidant enzymes activity and amino acid content of barley seed-lings were differently regulated in response to the isoosmotic condition of salt and drought stress.