• Molecules and Cells
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• v.38 no.9
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• pp.796-805
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• 2015

Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer's disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using wild-type and AD animal models. Gintonin induced $[Ca^{2+}]_i $ transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated $[Ca^{2+}]_i $ transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin-enriched fraction (25, 50, or 100 mg/kg, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 1 2 weeks) also significantly attenuated amyloid-${\beta}$ protein ($A{\beta}$)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltransferase (ChAT) activity and immunoreactivity, and increased acetylcholine esterase (AChE) activity. In a transgenic AD mouse model, long-term oral administration of gintonin (25 or 50 mg/kg, 3 months) also attenuated AD-related cholinergic impairments. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to $A{\beta}$ and could be utilized for AD prevention or therapy.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.401-407
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• 2021

Background: Gintonin is an exogenous ginseng-derived G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. LPA induces in vitro morphological changes and migration through neuronal LPA1 receptor. Recently, we reported that systemic administration of gintonin increases blood-brain barrier (BBB) permeability via the paracellular pathway and its binding to brain neurons. However, little is known about the influences of gintonin on in vivo neuron morphology and migration in the brain. Materials and methods: We examined the effects of gintonin on in vitro migration and morphology using primary hippocampal neural precursor cells (hNPC) and in vivo effects of gintonin on adult brain neurons using real time microscopic analysis and immunohistochemical analysis to observe the morphological and locational changes induced by gintonin treatment. Results: We found that treating hNPCs with gintonin induced morphological changes with a cell rounding following cell aggregation and return to individual neurons with time relapses. However, the in vitro effects of gintonin on hNPCs were blocked by the LPA1/3 receptor antagonist, Ki16425, and Rho kinase inhibitor, Y27632. We also examined the in vivo effects of gintonin on the morphological changes and migration of neurons in adult mouse brains using anti-NeuN and -neurofilament H antibodies. We found that acute intravenous administration of gintonin induced morphological and migrational changes in brain neurons. Gintonin induced some migrations of neurons with shortened neurofilament H in the cortex. The in vivo effects of gintonin were also blocked by Ki16425. Conclusion: The present report raises the possibility that gintonin could enter the brain and exert its influences on the migration and morphology of adult mouse brain neurons and possibly explains the therapeutic effects of neurological diseases behind the gintonin administration.

• Journal of Microbiology and Biotechnology
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• v.8 no.1
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• pp.81-88
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• 1998

The determination of appropriate parameters and parameter conditions is very important for the optimization of production of target materials. Taguchi's method has been used widely as the basis for development trials and optimization during industrial process design. Reaction variables which influence product yield are easily determined and their effects are revealed by just a few reactions, negating the need for extensive experimental investigation. There are usually some factors that are responsible for variations in process characteristics, so called noise factors. Controlling noise factors is very costly and difficult or impossible. Taguchi's experimental design method was examined to determine the control factor's level that is less sensitive to the changes in environmental conditions and other noise factors without control of noise factors. In this study, optimization of lipase-catalyzed production of lysophosphatidic acid (LPA) which has various physiological functions was performed by Taguchi's method. We obtained LPA yields ($66.5\%$) with low variance (5.32) at 400 RPM, molar ratio of 40 : 3 (mol) (fatty acid: G-3-P), 48 h, and $50^{\circ}C$. Thus, bioactive LPA with a desired fatty acid moiety could be produced with high yields and low variance despite various environmental noise factors.

• The Journal of Korean Institute of Electromagnetic Engineering and Science
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• v.11 no.8
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• pp.1407-1413
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• 2000

This paper presents a feedforward linear power amplifier (LPA) using error feedback technique to achieve low intermodulation distortions(IMD) of power amplifiers for base stations. Especially, the proposed linear power amplifier is applied to feedforward technique combined with error feedback technique, which has no loss of amplifier gain unlike typical feedback technique. The proposed LPA is designed by using HP ADS ver. 1.3, fabricated. When two-tone signals at 1850 MHz and 1851.25 MHz with -7 dBm/tone from synthesizers are injected into the main power amplifier with gain of 28 dB and P1dB of 1W, the proposed LPA could reduce more than 35 dB.

• Journal of Animal Science and Technology
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• v.53 no.3
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• pp.203-209
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• 2011

Lysophosphatidic acid (LPA) is a small lipid molecule that plays an important role through LPA receptors (LPARs) in reproductive processes. Our previous study has shown maximal expression of LPAR3 in the uterine endometrium on day (D) 12 of pregnancy in pigs, the period when conceptus secretes various molecules such as estrogen and interleukin-$1{\beta}$ (IL1B) and initiates implantation. We determined that endometrial expression of LPAR3 was increased by conceptus estrogen in the previous study, but the effect of IL1B on LPAR3 expression has not been determined. Thus, in this study we examined whether LPAR3 expression was also affected by IL1B. Endometrial explant cultures from D12 of the estrous cycle showed that levels of endometrial LPAR3 expression did not changed in response to IL1B. We also investigated LPAR3 expression in the uterine endometrium on D12 and D30 of pregnancy from gilts with conceptuses derived from somatic cell nuclear transfer (SCNT). The expression of LPAR3 mRNA was lower in endometria from gilts with conceptuses resulting from SCNT compared with those from gilts with embryos resulting from natural mating on D12 of pregnancy, but it was not different between them on D30 of pregnancy. Our results indicate that estrogen of conceptus origin is responsible for induction of LPAR3 expression during the peri-implantation period and appropriate LPA signaling is impaired in the uterine endometrium with SCNT-derived conceptuses during the implantation period in pigs.

• Clinical and Experimental Pediatrics
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• v.59 no.4
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• pp.183-189
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• 2016

Purpose: This study aimed to evaluate the correlation, according to postnatal age, between plasma B-type natriuretic peptide (BNP) levels and echocardiographic parameters for the assessment of patent ductus arteriosus (PDA) in preterm infants with respiratory distress. Methods: We enrolled 42 preterm infants with respiratory distress who underwent serial echocardiographic evaluation with simultaneous plasma BNP measurements until ductal closure. The correlations between BNP levels and the following 4 representative echocardiographic parameters were studied: diameter of the ductus arteriosus (DA), ratio of the left atrial diameter to the aortic diameter (LA/Ao), ratio of the PDA diameter to the infant's left pulmonary artery diameter (PDA/LPA), and the antegrade diastolic flow of LPA (DFLPA). Results: BNP levels were significantly correlated to the magnitude of the ductal shunt, comprising the DA diameter, PDA/LPA ratio, LA/Ao ratio, and antegrade DFLPA for the overall study period. The earliest significant correlation, starting from postnatal day 2, was observed between the LA/Ao ratio and BNP levels. The PDA/LPA ratio and the antegrade DFLPA showed significant correlations with BNP levels postnatal day 3 onward, and with the DA diameter, postnatal day 5 onward. Conclusion: BNP levels and echocardiographic parameters showed a positive correlation, but the significance of the correlations differed according to the postnatal age, especially during the first few days of life.

• Journal of the Korean Society of Environmental Restoration Technology
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• v.20 no.1
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• pp.131-142
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• 2017

The function of urban parks as wildlife habitats is becoming increasingly important. The urban park serves as a key area for preserving urban biodiversity. The purpose of this study is to estimate the bird species diversity in 30 parks in Cheonan city and quantitatively analyze the influence of vegetation, park structure and landscape connectivity index. As the results, a total of 27 birds species and 1,509 individuals were found at the sites and the largest number of birds were found in the Cheongsa park with 17 species. The optimal regression model was selected as the explanatory variables for the logged park area (LPA), the tree cover ratio (Co_T) and the patch betweenness centrality (PB). LPA and Co_T mean the internal characteristics of the park, and PB was the external environmental variable meaning landscape connectivity. LPA was the most important factor (73.3%) as bird habitat, and the PB could be interpreted as a factor that should be considered as important (26.7%). It will be possible to consider these environmental variables in the park and green area construction and management.

• Toxicological Research
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• v.22 no.4
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• pp.397-402
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• 2006

Lipid mediator such as lysophosphatidic acid (LPA) plays an important role in inflammation and wound heating, has been recently reported to induce influx of extracellular calcium into erythrocytes. This elevation in intracellular calcium level may cause destruction of membrane asymmetry and procoagulant microvesicle formation. Thus, we investigated if the lipid mediator could induce microvesicle formation as a result of extracellular calcium influx in human erythrocytes. Treatment with lipid mediator to erythrocytes resulted in microvesicle generation In a concentration-, time-dependent manner. Microvesicles formed expressed procoagulant phosphatidylserine (PS) on their surface membrane significantly as well. LPA did not affect the band 3 phosphorylation which is involved in morphological change in erythrocytes. Pretreatment with suramin did not inhibit LPA-induced microvesicle generation, suggesting microvesicle generation was not receptor-dependent pathway. Depletion of intracellular ATP levels in erythrocytes was suggested to be one of the mechanism for these events.

• Tuberculosis and Respiratory Diseases
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• v.83 no.4
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• pp.289-294
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• 2020

Background: Line probe assay (LPA) is standard diagnostic tool to detect multidrug resistant tuberculosis. Non-interpretable (NI) results in LPA (complete missing or light wild-type 3 and 8 bands with no mutation band in rpoB gene region) poses a diagnostic challenge. Methods: Sputum samples obtained between October 2016 and July 2017 at the Intermediate Reference Laboratory, All India Institute of Medical Sciences Hospital, New Delhi, India were screened. Smear-positive and smear-negative culture-positive specimens were subjected to LPA Genotype MTBDRplus Ver 2.0. Smear-negative with culture-negative and culture contamination were excluded. LPA NI samples were subjected to phenotypic drug susceptibility testing (pDST) using MGIT-960 and sequencing. Results: A total of 1,614 sputum specimens were screened and 1,340 were included for the study (smear-positive [n=1,188] and smear-negative culture-positive [n=152]). LPA demonstrated 1,306 (97.5%) valid results with TUB (Mycobacterium tuberculosis) band, 24 (1.8%) NI, three (0.2%) valid results without TUB band, and seven (0.5%) invalid results. Among the NI results, 22 isolates (91.7%) were found to be rifampicin (RIF) resistant and two (8.3%) were RIF sensitive in the pDST. Sequencing revealed that rpoB mutations were noted in all 22 cases with RIF resistance, whereas the remaining two cases had wild-type strains. Of the 22 cases with rpoB mutations, the most frequent mutation was S531W (n=10, 45.5%), followed by S531F (n=6, 27.2%), L530P (n=2, 9.1%), A532V (n=2, 9.1%), and L533P (n=2, 9.1%). Conclusion: The present study showed that the results of the Genotype MTBDRplus assay were NI in a small proportion of isolates. pDST and rpoB sequencing were useful in elucidating the cause and clinical meaning of the NI results.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.390-400
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• 2021

Background: We recently showed that gintonin, an active ginseng ingredient, exhibits antibrain neurodegenerative disease effects including multiple target mechanisms such as antioxidative stress and antiinflammation via the lysophosphatidic acid (LPA) receptors. Amyotrophic lateral sclerosis (ALS) is a spinal disease characterized by neurodegenerative changes in motor neurons with subsequent skeletal muscle paralysis and death. However, pathophysiological mechanisms of ALS are still elusive, and therapeutic drugs have not yet been developed. We investigate the putative alleviating effects of gintonin in ALS. Methods: The G93A-SOD1 transgenic mouse ALS model was used. Gintonin (50 or 100 mg/kg/day, p.o.) administration started from week seven. We performed histological analyses, immunoblot assays, and behavioral tests. Results: Gintonin extended mouse survival and relieved motor dysfunctions. Histological analyses of spinal cords revealed that gintonin increased the survival of motor neurons, expression of brain-derived neurotrophic factors, choline acetyltransferase, NeuN, and Nissl bodies compared with the vehicle control. Gintonin attenuated elevated spinal NAD(P) quinone oxidoreductase 1 expression and decreased oxidative stress-related ferritin, ionized calcium-binding adapter molecule 1-immunoreactive microglia, S100β-immunoreactive astrocyte, and Olig2-immunoreactive oligodendrocytes compared with the control vehicle. Interestingly, we found that the spinal LPA1 receptor level was decreased, whereas gintonin treatment restored decreased LPA1 receptor expression levels in the G93A-SOD1 transgenic mouse, thereby attenuating neurological symptoms and histological deficits. Conclusion: Gintonin-mediated symptomatic improvements of ALS might be associated with the attenuations of neuronal loss and oxidative stress via the spinal LPA1 receptor regulations. The present results suggest that the spinal LPA1 receptor is engaged in ALS, and gintonin may be useful for relieving ALS symptoms.