• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2022.05a
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• pp.270-272
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• 2022

Safety is one of the factors that prevent clinical drugs from being distributed on the market. In the case of neurotoxicity, which is the main cause of safety problems caused by drug side effects, risk assessment of drugs and compounds is required in advance. Currently, experiments for testing drug safety are based on animal experimetns, which have the disadvantage of being time-consuming and expensive. Therefore in order to solve the above problem, a neurotoxic prediction model through an in silico experiment was suggested. In this study, the category of neurotoxicity was expanded using a unified medical language system and various related compound data were obtained based on an integrated database. The SMILES (Simplified Molecular Input Line Entry System) of the obtained compounds were converted into fingerprints and it is used as input of machine learning. The model finally predicts the presence or absence of neurotoxicity. The experiment proposed in this study can reduce the time and cost required for the in vivo experiment. Furthermore, it is expected to shorten the research period for new drug development and reduce the burden of suspension of development.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.411-416
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• 2023

Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.

• Archives of Craniofacial Surgery
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• v.24 no.5
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• pp.218-222
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• 2023

Background: Botulinum toxin is a neurotoxic substance with a wide range of uses, from the treatment of musculoskeletal spasms to anti-aging regimens by improving wrinkles. Split-face studies in which drugs are injected in the right and left sides of the faces have been actively conducted in botulinum toxin studies. In this study, we aimed to investigate the reliability of a split-face study for determining the effectiveness of botulinum toxin based on eyebrow height and movement, and electromyography results. Methods: Thirty-one women aged 35 to 55 years were included in the study. Eyebrow height was measured as the distance from the eyebrows to the upper eyelid margin on the primary gaze, and eyebrow movement was measured as the distance when the forehead was wrinkled for 5 seconds. A noninvasive method was used for electromyography of the frontalis muscles. Results: No statistically significant differences in right and left eyebrow heights and movements, and electromyography findings (p= 0.256, p= 1.000, and p= 0.978, respectively) were found. Pearson correlation analysis showed that electromyography muscle activity is positively associated with eyebrow movement, respectively (p< 0.001). Conclusion: We advocate the reliability of split-face study and the usefulness of electromyography of frontalis muscle in forehead rejuvenation research.

• Journal of Preventive Medicine and Public Health
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• v.31 no.4 s.63
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• pp.692-707
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• 1998

Aim. A neurobehavioral test for workers exposed to organic solvents in the workplace can be affected by many factors : age, education, motivation, ethnicity, etc. To apply more suitable neurobehavioral test for Korean workers, we evaluated the validity of several items of computerized and traditional neurobehavioral tests. Methods. We have applied eleven tests : four items of computerized neurobehavioral test(Swedish Performance Evaluation System) including Addition, Symbol-Digit, Dig-it Span, and Finger tapping speed, and seven items of traditional neurobehavioral test consisting of Addition, Digit-Symbol, Digit Span, Benton visual retention test, Pursuit aiming, Pegboard, and Tapping. These tests were performed on 96 workers exposed to solvents, and 100 reference workers. The concurrent and construct validities were evaluated by group difference, correlation with age, educational level, hippuric acid level, neurotoxic symptom, current exposure level, multitrait-multimethod matrix, fator analysis, and discriminant analysis. Results. Statistically significant differences were observed between the workers exposed to solvents and referents in computerized Symbol-Digit, Finger tapping speed, traditional Digit-Symbol and Pegboard. The computerized Symbol-Digit, traditional Digit-Symbol, Addition, Benton visual retention test, and Pegboard were found to be related to the age. The performance of computerized Symbol-Digit, Addition, and traditional Digit-Symbol were found to be related to the educational level significantly. The computerized Symbol-Digit, Finger tapping speed, and traditional Digit-Symbol were found to be related to hippuric acid, and neurotoxic symptom. The discriminability of Finger tapping speed, and Pegboard was better than the other tests. In discriminant analysis, the model with two variables, the computerized Symbol-Digit and Pegboard, classified almost 70 percent of the workers correctly. Conclusions. These results suggest that the computerized Symbol-Digit, Finger tapping speed, and Pegboard are more satisfactory for our purpose, and the Addition, Tapping, Benton visual retention test, and Pursuit aiming are less valid than other items. These may allow the reasonable selection of core neurobehavioral tests for workers exposed to solvents in Korea.

• Journal of Life Science
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• v.19 no.4
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• pp.449-456
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• 2009

Murine Neuro-2a (N2a) cells have been widely used for the investigation of neuronal differentiation, trophic interaction and neurotoxic effects of various compounds and their associated mechanisms. N2a cells have many genomic variations such as gains or losses in DNA copy number, similar to other neuroblastoma cells, and no systematic or high-resolution studies of their genome-wide chromosomal aberrations have been reported. Presently, we conducted a systematic genome-wide determination of chromosomal aberrations in N2a cells using a high-throughput, oligonucleotide array-based comparative genomic hybridization (oaCGH) technique. A hidden Markov Model was employed to assign each genomic oligonucleotide to a DNA copy number state: double loss, single loss, normal, gain, double gain and amplification. Unlike most neuroblastoma cells, Mycn amplification was not observed in N2a cells. In addition, these cells showed gain only in the neuron-derived neurotrophic factor (NF), while other neurotrophic factors such as glial line-derived NF and brain-derived NF presented normal copy numbers. Chromosomes 4, 8, 10, 11 and 15 displayed more than 1000 aberrational oligonucleotides, while chromosomes 3, 17, 18 and 19 displayed less than 20. The largest region of gain was located on chromosome 8 and its size was no less than 26.7 Mb (Chr8:8427841-35162415), while chromosome 4 had the longest region of single deletion, with a size of 15.1 Mb (Chr4:73265785-88374165).

• Proceedings of the Korean Environmental Health Society Conference
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• 2005.12a
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• pp.4-15
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• 2005

Methylmercury (MeHg) is an environmental pollutant with neurotoxic effects on the central nervous system. The major exposure route of MeHg to humans is via consumption of fish and shellfish which accumulate the chemical through the food web in an aquatic environment. Hair mercury level is an excellent marker for MeHg exposure. We have been conducting a survey on hair mercury contents among general populations from 14 districts to estimate the current Japanese MeHg exposure level. Total mercury levels of all hair samples collected (12923 in total) were analyzed by the oxygen combustion-gold amalgamation method using an atomic absorption mercury detector. Multiple regression analysis revealed that mercury levels were significantly correlated with several covariates, such as sex, age, the amount of daily intake of total fish/shellfish, a preference for certain fish such as tuna or bonito, and artificial waving. The geometric means for the population without artificial waving were 2.47 and 1.65 ${\mu}g/g$ for males (n = 5623) and females (n = 3470), respectively. Hair mercury levels varied with age, and the variations were more significant in males. Since the difference between sexes was not evident at younger ages, some hormonal control might also be involved in the mercury uptake by human hair. The average mercury levels in our hair samples varied among the sampling districts. Tuna is a major carnivorous fish with high mercury accumulations that is often consumed in Japan. The amount of fish consumption and the preference rate far tuna would appear to be responsible far the regional variation in hair mercury levels in Japan. Recently, a provisional tolerable weekly intake (PTWI) of MeHg was revised by 61st JECFA to 1.6 ${\mu}g/kg/week$, which was about half that of the Japanese standard, and corresponded to a hair level of 2.2 ppm. The distribution of hair mercury levels in Japanese populations in the present study indicated that 25% of the Japanese females of child-bearing age were estimated to be exposed to MeHg over the PTWI level. This would reflect the high Japanese consumption of marine products. However, not only mercury contamination, but also the nutritional benefit may have to be considered when discussing the risk involved in the current level of fish and shellfish consumption in Japan.

• BMB Reports
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• v.42 no.7
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• pp.444-449
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• 2009

Different neurodegenerative disorders like prion disease, is caused by protein misfolding conformers. Reverse-transfected cytosolic prion protein (PrP) and PrP expressed in the cytosol have been shown to be neurotoxic. To investigate the possible mechanism of neurotoxicity due to accumulation of PrP in cytosol, a PrP mutant lacking the signal and GPI (CytoPrP) was introduced into the SH-SY5Y cell. MTT and trypan blue assays indicated that the viability of cells expressing CytoPrP was remarkably reduced after treatment of MG-132. Obvious apoptosis phenomena were detected in the cells accumulated with CytoPrP, including loss of mitochondrial transmembrane potential, increase of caspase-3 activity, more annexin V/PI-double positive-stained cells and reduced Bcl-2 level. Moreover, DNA fragmentation and TUNEL assays also revealed clear evidences of late apoptosis in the cells accumulated CytoPrP. These data suggest that the accumulation of CytoPrP in cytoplasm may trigger cell apoptosis, in which mitochondrial relative apoptosis pathway seems to play critical role.

• Molecules and Cells
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• v.27 no.1
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• pp.105-111
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• 2009

Gammaherpesvirus infection of the central nervous system (CNS) has been linked to various neurological diseases, including meningitis, encephalitis, and multiple sclerosis. However, little is known about the interactions between the virus and the CNS in vitro or in vivo. Murine gammaherpesvirus 68 (MHV-68 or ${\gamma}HV-68$) is genetically related and biologically similar to human gammaherpesviruses, thereby providing a tractable animal model system in which to study both viral pathogenesis and replication. In the present study, we show the successful infection of cultured neuronal cells, microglia, and astrocytes with MHV-68 to various extents. Upon intracerebroventricular injection of a recombinant virus (MHV-68/LacZ) into 4-5-week-old and 9-10-week-old mice, the 4-5-week-old mice displayed high mortality within 5-7 days, while the majority of the 9-10-week-old mice survived until the end of the experimental period. Until a peak at 3-4 days post-infection, viral DNA replication and gene expression were similar in the brains of both mouse groups, but only the 9-10-week-old mice were able to subdue viral DNA replication and gene expression after 5 days post-infection. Pro-inflammatory cytokine mRNAs of tumor necrosis factor-${\alpha}$, interleukin $1{\beta}$, and interleukin 6 were highly induced in the brains of the 4-5-week-old mice, suggesting their possible contributions as neurotoxic factors in the age-dependent control of MHV-68 replication of the CNS.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.6
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• pp.1500-1508
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• 2003

This study was performed to clarify the neurotoxic mechanism of nerve cells damage by brain ischemia. The cytotoxic effect of ischemia was determined by XTT assay, NR assay, superoxide dismutase(SOD) activity, amount of malondialdehyde(MDA), lactate dehydrogenase(LDH) activity, protein synthesis and tumor necrosis factor(TNF)-α activities after cerebral neurons derived from mouse were exposed to ischemia for 1∼30 minutes. In addition, the protective effect of extract of Daejo-whan(DJW) on ischemia-induced neurotoxicity was examined in these cultures. 1. Ischemia decreased cell number and viability by XTT assay or NR assay when cultured cerebral neurons were exposed to 95% N2/5% CO₂ for 1∼20 minutes in these cultures. 2. Ischemia decreased SOD and protein syntheses, but it increased amount of MDA and, LDH and TNF-α activities in these cultures. 3. In the neuroprotective effect of DJW extracts on cerebral neurons damaged by ischemia, DJW extracts increased SOD activity and protein synthesis. While, it decreased amount of MDA and, LDH and TNF-α activities after cerebral neurons preincubated with herb extracts. It suggests that brain ischemia has neurotoxicity on cultured mouse cerebral neurons, and the herb extract such as DJW was very effective in blocking the neurotoxicity induced by ischemia in cultured mouse cerebral neurons.

• Microbiology and Biotechnology Letters
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• v.6 no.1
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• pp.41-46
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• 1978

Piscicidal substance produced by Streptomyces sp. isolated from soil was toxic against various kinds of fish. After extraction with CH$Cl_3$ from the culture medium, the substance was purified by avicel column chromatography. In order to test toxicity, various kinds of fish were subjected to the acqueous solution of 100 us of the substance per liter of water. Generally, the substance was toxic to most fish, but Macropodus chinenes and Misgurnus mizolepis are resistant to the substance than Gobius similis and Pseudorasbora parva. The substance was stable at pH range, 3.0 to 7.0, but labile at alkaline pH, and to heat as well. Succinic dehydrogenase on most of tissue cell of Cyprinus carpio was inhibited by this substance strongly, but spinal cord was not inhibited. By addition of Cu and Pb salts to the culture medium, piscicidal substance producibility was activated.