• Biomolecules & Therapeutics
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• v.21 no.3
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• pp.222-228
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• 2013

Although the role of ${\alpha}$-synuclein aggregation on Parkinson's disease is relatively well known, the physiological role and the regulatory mechanism governing the expression of ${\alpha}$-synuclein are unclear yet. We recently reported that ${\alpha}$-synuclein is expressed and secreted from cultured astrocytes. In this study, we investigated the effect of valproic acid (VPA), which has been suggested to provide neuroprotection by increasing ${\alpha}$-synuclein in neuron, on ${\alpha}$-synuclein expression in rat primary astrocytes. VPA concentration-dependently increased the protein expression level of ${\alpha}$-synuclein in cultured rat primary astrocytes with concomitant increase in mRNA expression level. Likewise, the level of secreted ${\alpha}$-synuclein was also increased by VPA. VPA increased the phosphorylation of Erk1/2 and JNK and pretreatment of a JNK inhibitor SP600125 prevented the VPA-induced increase in ${\alpha}$-synuclein. Whether the increased ${\alpha}$-synuclein in astrocytes is involved in the reported neuroprotective effects of VPA awaits further investigation.

• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1152-1156
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• 2009

Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson’s disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.

• KSBB Journal
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• v.20 no.1 s.90
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• pp.21-25
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• 2005

Paraquat, a widely used herbicide, has been suggested as a potential risk factor for Parkinson's disease. Heme oxygenase-1(HO-1), a marker for oxidative stress and endoplasmic reticulum(ER) stress, is known to catalyze heme to biliverdin, carbon monoxide and free iron in response to various stimuli. Here we show that paraquat activates HO-1 expression in a time-and dose-dependent manner in substantia nigra(SN) dopaminergic neuronal cells. Activation of Ho-1 by paraquat was regulated primarily at the level of gene transcription. Deletion analysis of the promoter and the 5' distal enhancers, E1 and E2, of the HO-1 gene revealed that the E2 enhancer is a potent inducer of the paraquat-dependent Ho-1 gene expression in dopamninergic neuronal cells. Mutational analysis of the E2 enhacer further demonstrated that the transcription factor activator protein-1(AP-1) plays an important role in mediating paraquat-induced HO-1 gene transcription. Moreover, using specific inhibitors of the mitogen-activated protein kinases(MAPKs), we investigated the role of paraquat and MAPKs for HO-1 gene regulation in dopaminergic cells. The c-Jun N-terminal kinase(JNK) inhibitor SP600125 significantly suppressed the expression of HO-1 by paraquat. All these results demonstrate that induction of HO-1 by paraquat requies the activation of the AP-1 and JNK pathway.

• The Journal of Korea Institute of Information, Electronics, and Communication Technology
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• v.12 no.4
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• pp.413-418
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• 2019

Studies are now actively underway to confirm the degree of treatment and rehabilitation of patients with brain-related diseases (dementia, schizophrenia, depression, Parkinson's disease). Among them, Transcranial magnetic stimulation (TMS) is widely used in treatment because it is a technique that is used for noninvasive brain neuron control in patients with brain disorders. It can be seen that muscle fatigue of normal people increases during Transcranial magnetic stimulation. Therefore, in this paper, our purpose is to build an EMG measurement system to measure motor neuron-induced response during transcranial magnetic stimulation and We identify a motor-neutral response system using tendency in the RMS graph. As an experimental method, the Raw Data received through the surface EMG device and analyzed by RMS technique, after the contraction and relaxation movement of the biceps brachii. As a result of the experiment, we confirmed the trend of rising RMS graph, and it will can be used to determine the self-stimulation intensity for each individual in consideration of the data of the motor-neutral response.

• Journal of the Korean Society of Radiology
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• v.15 no.4
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• pp.555-564
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• 2021

Thalamus is known to play an important role in the regulation of nerve function. Thalamus, located in the center of the brain, is involved in sleep, arousal, and emotional regulation, and has been reported to be associated with multiple sclerosis, essential tremors, and neurodegenerative diseases such as Parkinson's disease. In addition, it has been reported that iron deposits in the thalamus can cause depressive symptoms with age. Although there are discrepancies between studies, it can be deduced that the thalamus region has a clear effect on neurological disorders due to a strong relationship between the thalamus and neurological functions such as emotional control and processing. Through tractography analysis, the connectivity between the detailed areas of each subcortical region was investigated in the form of a matrix, showing strong connectivity and weak interhemispheric connectivity. In the 59> group, the WM connectivity of thalamus was found to be weaker than those of the two groups. Comparisons between the two groups showed that the young groups (10-39 and 40-59) had higher connection intensity than the 59> group and that statistically significant differences in 3 connection pathways were found in each hemisphere. A decrease in thalamus-related connection strength in aging has shown that it can affect emotional and neurological disorders such as anxiety and depression, and network measurements can help assess cognitive impairment across clinical conditions.

• The Journal of Korean Medicine
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• v.43 no.2
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• pp.1-7
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• 2022

Objectives: Bee venom (BV) is a widely used therapy in Traditional East Asian Medicine (TEAM). We previously reported that BV was clinically effective for treating Parkinson's disease, that phospholipase A₂ (PLA₂) was the main component of BV, and that it induced regulatory T cells (Tregs) by binding CD206 on dendritic cells (DCs). Therefore, we aimed to reconfirm our findings in human blood samples and investigate the relationship between CD206⁺ DCs and clinical syndrome differentiation in TEAM. Methods: We surveyed 100 subjects with questionnaires on cold-heat patternization and obtained their blood samples. The obtained human peripheral blood monocytes (hPBMCs) were washed with phosphate-buffered saline (PBS). After resuspension with ex vivo media, numbers of cells were counted. Tregs were counted after culturing the samples in a 37℃ CO₂ incubator for 72 h. Results: We divided the subjects into a relatively high CD206⁺ group or a relatively low CD206⁺ group. The heat factor scores of high CD206⁺ group were significantly higher than that of low CD206⁺ group (high vs low: 239.2 ± 54.1 vs 208.4 ± 55.1, p=0.023). After culturing with PLA₂, Tregs increased in the high CD206⁺ group but decreased in the low CD206⁺ group. Conclusion: In this study, we reconfirm that CD206⁺ DCs induced Treg differentiation by incubating human blood samples with PLA₂ and that they showed an association with syndrome differentiation, especially with heat patterns, in TEAM. A heat pattern in TEAM might be one indication for PLA₂ therapy because its score was elevated in the high CD206⁺ group.

• Journal of Life Science
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• v.32 no.10
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• pp.771-777
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• 2022

Dopaminergic (DA) cell death in Parkinson's disease (PD) has been attributed to multiple, distinct genetic and environmental factors. In rare familial PD loss of parkin function mutations play a key role in nigral DA neuron-specific pathogenesis primarily via endoplasmic reticulum (ER) stress. In more prevalent sporadic PD, environmental exposure to pesticides has a significant epidemiological role. However, it is largely unknown how environmental exposure to xenobiotics is etiologically linked with the known etiology in familial PD. In the present study biochemical evidence for a common pathogenic mechanism between sporadic and familial PD has been identified employing the recently characterized mesencephalic DA cell line, N27-A. Dieldrin, an organochlorine pesticide epidemiologically implicated in sporadic PD, induced the markers of ER stress response such as a chaperone BiP/Grp78, heme oxygenase-1 and especially, parkin. Accordingly, dieldrin activated the ER resident Caspase-12, a mediator of ER stress-specific apoptosis, during cell death of N27-A cells. Of great interest the dieldrin-induced DA neuronal cell death was synergistically rescued by the overexpression of ER resident neuroprotective proteins, parkin and Bcl-2. The present findings implicate that accumulation of ER stress could be one of common pathogenic mechanisms in idiopathic and familial PD, and some ER proteins, such as parkin and Bcl-2 may effectively attenuate ER stress-mediated N27-A DA cell death.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.298-306
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• 2022

This study sought to evaluate the mechanism of cellular injury caused by ferrous sulfate (FeSO₄) and the protective effects of Parnassia palustris L. (PP) extract against FeSO₄-induced cytotoxicity of cultured C6 glioma cells. FeSO₄ is known to cause neurotoxicity and induce Parkinson's disease. The antioxidative effects of PP, such as superoxide dismutase (SOD)-like and superoxide anion-radical (SAR)-scavenging activities, as well as effects on cell viability, were studied. FeSO₄ significantly decreased cell viability in a dose-dependent manner and the XTT₅₀ value, the concentration of FeSO₄ which reduced the cell viability by half, was measured at 63.3 μM in these cultures. FeSO₄ was estimated to be highly cytotoxic by the Borenfreund and Puerner toxicity criteria. Quercetin, an antioxidant, significantly improved cell viability, damaged by FeSO₄-induced cytotoxicity. While evaluating the protective effects of the PP extract on FeSO₄-induced cytotoxicity, it was observed that the extract significantly increased cell viability compared to the FeSO₄-treated group. Also, the PP extract showed superoxide dismutase (SOD)-like and superoxide anion radical (SAR)-scavenging activities. Based on these findings, it can be concluded that FeSO₄ induced oxidative stress-related cytotoxicity, and the PP extract effectively protected against this cytotoxicity via its antioxidative effects. In conclusion, natural antioxidant sources such as PP may be agents useful for preventing oxidative stress-related cytotoxicity induced by heavy metal compounds such as the FeSO₄, a known Parkinsonism inducer.

• The Journal of the Society of Stroke on Korean Medicine
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• v.16 no.1
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• pp.25-34
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• 2015

■ Objectives The purpose of this case report is to show the effect of korean medicine on a progressive supranuclear palsy patient with gait disturbance and dizziness. ■ Methods A patient with gait disturbance and dizziness diagnosed as progressive supranuclear palsy was treated with herbal medicine, acupuncture, electro-acupuncture, moxibustion. The period of admission is 16 days and we evauated the improvements of symptoms by the Unified Parkinson's Disease Rating Scale(UPDRS), Numeric Rating Scale(NRS) and Global Assessment(G/A). ■ Results After taking Modified Bosimhwan andbeing treated by acupuncture therapy, improvements of gait disturbance and dizziness are observed. ■ Conclusion This case report proved the effect of Korean medicine on progressive supranuclear palsy.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.2
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• pp.105-112
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• 2023

Leucine-rich repeat kinase 2 (LRRK2) is known to play a crucial role in the pathophysiology of neurodegenerative disorders such as Parkinson's disease. LRRK2 is predominantly expressed in the lung as well as the brain. However, it is unclear whether LRRK2 expression correlates with the pathogenesis of lung squamous cell carcinoma (LUSC). This study analyzes the prognostic significance of LRRK2 in LUSC using the Kaplan-Meier plotter tool. High expression of LRRK2 is known to be associated with a bad prognosis in patients with LUSC. Patients with high LRRK2 expression, tumor mutational burden, high neoantigen load, and even gender correlation reportedly have the worse survival rates. In the gene expression profiling interactive analysis (GEPIA) database, the severity of pathogenesis in LUSC with high LRRK2 expression positively corresponds to a high expression of anti-inflammatory cytokines but not inflammatory cytokines. Similarly, the increased expression of interleukin (IL)10-related genes was shown to be significantly linked in LRRK2-high LUSC patients having a poor prognosis. Moreover, the tumor immune estimation resource (TIMER) database suggests that macrophages are one of the cellular sources of IL10 in LRRK2-high LUSC patients. Collectively, our results demonstrate that the postulated LRRK2-IL10 axis is a potential therapeutic target and prognostic biomarker for LUSC.