• Nutrition Research and Practice
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• 제7권4호
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• pp.249-255
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• 2013

In this study, the protective effects of EGCG on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced oxidative cell death in catecholaminergic PC12 cells, the in vitro model of Parkinson's disease, were investigated. Treatment with L-DOPA at concentrations higher than $150{\mu}M$ caused cytotoxicity in PC12 cells, as determined using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry detection. The apoptotic ratio was similar in cells treated with $100{\mu}M$ EGCG plus $150{\mu}M$ L-DOPA (5.02%) and the control (0.96%) (P > 0.05), and was lower than that of cells treated with L-DOPA only (32.24%, P < 0.05). The generation level of ROS (% of control) in cells treated with EGCG plus L-DOPA was lower than that in cells treated with L-DOPA only (123.90% vs 272.32%, P < 0.05). The optical density in production of TBARS in cells treated with L-DOPA only was higher than that in the control ($0.27{\pm}0.05$ vs $0.08{\pm}0.04$, P < 0.05), and in cells treated with EGCG only ($0.14{\pm}0.02$, P < 0.05), and EGCG plus L-DOPA ($0.13{\pm}0.02$, P < 0.05). The intracellular level of GSH in cells treated with EGCG plus L-DOPA was higher than that in cells treated with L-DOPA only ($233.25{\pm}16.44$ vs $119.23{\pm}10.25$, P < 0.05). These results suggest that EGCG protects against L-DOPA-induced oxidative apoptosis in PC12 cells, and might be a potent neuroprotective agent.

• 대한치매학회지
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• 제17권4호
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• pp.148-155
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• 2018

Background and Purpose: Two conversion scales between the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) have been validated for Korean patients with Parkinson's disease. The aim of the present study was to validate these conversion scales for all patients with cognitive impairments regardless of dementia subtype. Methods: Medical records of 323 subjects who completed both MMSE and MoCA on the same day were retrospectively reviewed. Mean, median, and root mean squared error (RMSE) of the difference between true and equivalent MMSE scores were calculated. Intraclass correlation coefficients (ICCs) between true and equivalent MMSE scores were also calculated. The validity of MoCA-MMSE conversion scales was evaluated according to educational level (low educated: ${\leq}6$ years; high educated: ${\geq}7$ years) and subtypes of cognitive impairment. Results: The difference between true and equivalent MMSE scores had a median value of 0, a mean value of 0.19 according to the van Steenoven scale, a mean value of 0.57 according to the Lawton scale, RMSE value of 2.2 according to the van Steenoven scale, and RMSE value of 0.42 according to the Lawton scale. Additionally, ICCs between true and equivalent MMSE scores were 0.92 and 0.90 on van Steenovan and Lawton conversion scales, respectively. These results were maintained in subgroup analyses. Conclusions: Findings of the present study suggest that both van Steenovan and Lawton MoCA-MMSE conversion scales are applicable to transforming MoCA scores into MMSE scores in patients with cognitive impairments regardless of dementia subtype or educational level.

• 생물정신의학
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• 제27권2호
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• pp.64-73
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• 2020

Suicidality is the most serious complication of mood disorders and psychosis; effective treatment should reduce suicide rates. The Organization for Economic Cooperation and Development age-standardized suicide rate in Korea was 22.6 in 2018, much higher compared to other countries worldwide. As mental and psychiatric problems are the main reasons for suicide attempts, accounting for 31.6% in 2018, targeting such problems should be the focus of efforts to reduce suicide rates. However, the ability of current pharmacotherapeutic and psychotherapeutic interventions to reduce suicide rates is limited due to their delayed effects. Therefore, electroconvulsive therapy (ECT) has been proposed as an alternative treatment. This approach is effective for treating most mental disorders associated with high suicide rates, including severe depression, bipolar disorder, and intractable psychotic disorders; ECT is also effective for Parkinson's disease, which has the highest suicide rate among all disorders in Korea. The acute, long-term, and prophylactic effects of ECT on suicidality have been reported in the literature, and treatment guidelines outside of Korea recommend that ECT be used at an early stage for rapid reduction of suicide rates, as opposed to being applied as a treatment of last resort. However, only ~0.092 of every 10000 members of the Korean general population received ECT in 2018; this is much lower than the average rate worldwide, of 2.2 per 10000. Elimination of obstacles to the use of ECT, early crisis intervention involving administration of ECT for rapid stabilization, and maintenance ECT to prevent recurrence should reduce suicide rates.

• Molecules and Cells
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• 제42권10호
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• pp.702-710
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• 2019

Neuroinflammation is an important contributor to the pathogenesis of neurodegenerative disorders including Parkinson's disease (PD). We previously reported that our novel synthetic compound KMS99220 has a good pharmacokinetic profile, enters the brain, exerts neuroprotective effect, and inhibits $NF{\kappa}B$ activation. To further assess the utility of KMS99220 as a potential therapeutic agent for PD, we tested whether KMS99220 exerts an anti-inflammatory effect in vivo and examined the molecular mechanism mediating this phenomenon. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, oral administration of KMS99220 attenuated microglial activation and decreased the levels of inducible nitric oxide synthase and interleukin 1 beta ($IL-1{\beta}$) in the nigrostriatal system. In lipopolysaccharide (LPS)-challenged BV-2 microglial cells, KMS99220 suppressed the production and expression of $IL-1{\beta}$. In the activated microglia, KMS99220 reduced the phosphorylation of $I{\kappa}B$ kinase, c-Jun N-terminal kinase, and p38 MAP kinase; this effect was mediated by heme oxygenase-1 (HO-1), as both gene silencing and pharmacological inhibition of HO-1 abolished the effect of KMS99220. KMS99220 induced nuclear translocation of the transcription factor Nrf2 and expression of the Nrf2 target genes including HO-1. Together with our earlier findings, our current results show that KMS99220 may be a potential therapeutic agent for neuroinflammation-related neurodegenerative diseases such as PD.

• 동의생리병리학회지
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• 제34권5호
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• pp.269-278
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• 2020

The purpose of this study is to report the effect of the Korean acupuncture treatment and Open Wet Dressing Therapy(OPWT) for pressure ulcer. From November 2015 to January 2020, 9 patients with 3rd or 4th graded pressure ulcer over 70 years of age who were admitted to a care hospital with underlying diseases such as cerebral infarction, brain hemorrhage, and Parkinson's disease were treated by acupuncture and OPWT. Photographs of lesions were used to evaluate the changes in condition of pressure ulcer. Acupuncture was performed 4 times a week along the border between the normal epidermal region and the pressure ulcer granulation tissue in contact with the pressure ulcer interface. OPWT to create a wet environment for wounds by washing the wounds 1-2 times a day with normal saline solution and covering them with food wrap was combined. In addition, for objective treatment progress evaluation, size, stage and condition of pressure ulcer were regularly monitored using the classification method of The National Pressure Ulcer Advisory Panel (NPUAP) according to the condition and depth of the damaged tissue and The Pressure Ulcer Scale for Healing(PUSH tool 3.0). After acupuncture treatment and OPWT, the pressure ulcer of patients was cured in as short as 66 days and as long as 274 days (average 170 days). This study shows that acupuncture treatment and OPWT were effective to treat pressure ulcer.

• Molecules and Cells
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• 제45권10호
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• pp.749-760
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• 2022

Osteoclast generation from monocyte/macrophage lineage precursor cells needs to be tightly regulated to maintain bone homeostasis and is frequently over-activated in inflammatory conditions. PARK2, a protein associated with Parkinson's disease, plays an important role in mitophagy via its ubiquitin ligase function. In this study, we investigated whether PARK2 is involved in osteoclastogenesis. PARK2 expression was found to be increased during the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. PARK2 gene silencing with siRNA significantly reduced osteoclastogenesis induced by RANKL, LPS (lipopolysaccharide), TNFα (tumor necrosis factor α), and IL-1β (interleukin-1β). On the other hand, overexpression of PARK2 promoted osteoclastogenesis. This regulation of osteoclastogenesis by PARK2 was mediated by IKK (inhibitory κB kinase) and NF-κB activation while MAPK (mitogen-activated protein kinases) activation was not involved. Additionally, administration of PARK2 siRNA significantly reduced osteoclastogenesis and bone loss in an in vivo model of inflammatory bone erosion. Taken together, this study establishes a novel role for PARK2 as a positive regulator in osteoclast differentiation and inflammatory bone destruction.

• Mass Spectrometry Letters
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• 제13권4호
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• pp.146-151
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• 2022

Rotigotine (RTG) is a non-ergot dopamine agonist used to manage the early stage of Parkinson's disease (PD) as transdermal patch. However, the poor medication compliance of PD patients and skin issues related with repeated applications of RTG patches lead to the search for alternative formulations and it also requires appropriate analytical methods for their in vivo evaluation. Thus, here, a sensitive, efficient, and cost-effective method to determine RTG in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was developed. The use of 20 µL of rat plasma for sample treatment, 8-OH-DPAT as the internal standard, and methyl tert-butyl ether as the LLE solvent in the present method gives it advantages over previous methods for the analysis of RTG in biological samples. The good analytical performance of the developed method was confirmed in specificity, linearity (the coefficient of determination ≥0.999 within 0.1-100 ng/mL), sensitivity (the lower limit of quantitation at 0.1 ng/mL), accuracy (81.00-115.05%), precision (≤10.75%), and recovery (81.00-104.48%) by following the FDA guidelines. Finally, the applicability test of the validated method to the in vivo evaluation of a RTG formulation showed that the present method is the only method which can be accurately applied to that longer than 24 hours, critical for the development of formulations with reduced dosing frequencies. Therefore, the present method could contribute to the development of new RTG formulations helpful to people suffering from PD.

• 대한한방내과학회지
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• 제42권6호
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• pp.1356-1365
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• 2021

This study examined the effectiveness of Korean medical treatment in a patient with persistent drug-induced parkinsonism after drug discontinuation. The changes in symptoms were assessed using the unified parkinson's disease rating scale (UPDRS), postural instability-gait disturbance (PIGD) score, and the 20 m gait time and steps. After 22 days of hospitalization, the UPDRS, PIGD score, and 20 m gait time and steps showed clinically significant improvement. The improvement persisted after discharge. This study indicated that Korean medical treatment could be an effective alternative therapy for treating persistent drug-induced parkinsonism after drug discontinuation.

• Biomolecules & Therapeutics
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• 제31권3호
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• pp.264-275
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• 2023

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a well-known neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

• 대한한방내과학회지
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• 제44권2호
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• pp.187-196
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• 2023

Objective: This case study reported the effectiveness of adjuvant Korean therapy on gait disturbances induced by drug-induced Parkinsonism. Method: A patient suffering from frontotemporal lobe dementia was diagnosed with drug-induced Parkinsonism and treated with adjuvant Korean therapy, including herbal medicine and pharmaco-acupuncture. The evaluation was performed by monitoring the length of time and number of steps during an 8 m gait, using the Unified Parkinson's Disease Rating Scale (UPDRS). Results: After 17 days of adjuvant Korean therapy, the UPDRS score improved from 32 to 16. The length of time for the 8 m gait improved from 20 seconds to 14 seconds. The patient also showed a decrease in the number of steps during the 8 m gait from 43 to 22. Conclusion: This case suggests that adjuvant Korean therapy can be effective for drug-induced Parkinsonism.