• BMB Reports
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• v.55 no.1
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• pp.20-29
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• 2022

Stem cell-based therapy is a promising approach for treating a variety of disorders, including acute brain insults and neurodegenerative diseases. Stem cells such as mesenchymal stem cells (MSCs) secrete extracellular vesicles (EVs), circular membrane fragments (30 nm-1 ㎛) that are shed from the cell surface, carrying several therapeutic molecules such as proteins and microRNAs. Because EV-based therapy is superior to cell therapy in terms of scalable production, biodistribution, and safety profiles, it can be used to treat brain diseases as an alternative to stem cell therapy. This review presents evidences evaluating the role of stem cell-derived EVs in stroke, traumatic brain injury, and degenerative brain diseases, such as Alzheimer's disease and Parkinson' disease. In addition, stem cell-derived EVs have better profiles in biocompatibility, immunogenicity, and safety than those of small chemical and macromolecules. The advantages and disadvantages of EVs compared with other strategies are discussed. Even though EVs obtained from native stem cells have potential in the treatment of brain diseases, the successful clinical application is limited by the short half-life, limited targeting, rapid clearance after application, and insufficient payload. We discuss the strategies to enhance the efficacy of EV therapeutics. Finally, EV therapies have yet to be approved by the regulatory authorities. Major issues are discussed together with relevant advances in the clinical application of EV therapeutics.

• Phonetics and Speech Sciences
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• v.2 no.4
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• pp.75-82
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• 2010

Many previous studies based on respiratory characteristics of Idiopathic Parkinson's Diseases (IPD) patients have not controlled related factors appropriately. Accordingly, these studies produced discordant results. Furthermore, there is currently a lack of studies that can provide precise explanations on the characteristics of respiration and phonation. This study included a total of 40 subjects: 20 mixed gender de novo IPD patients ranging in age from 50 to 80 (Hoehn & Yahr stage 1~3), and 20 normal subjects with similar matches for age and gender. All participants were controlled based on their gender, age, height, weight, vocal fold function, cognitive abilities, and depression factors. K-MMSE (Korean-Mini Mental State Examination), nVHI-10 (new Voice Handicap Index), and KGDS (Korean Form of Geriatric Depression Scale) were evaluated to select this study subjects. In order to compare respiratory functions between the two groups, FVC, FEV1, and FEV1/FVC were measured using microQuark, a PC-based spirometer. CSL was used by measure MPT and PAS was used to measure MFR. To investigate the characteristics of phonation ability, CSL was used to measure jitter and shimmer, while PAS was used to measure Psub. In order to compare the respiratory function averages and phonation ability between the two groups, statistical analysis was conducted using SPSS (version 12.0). The results of this study showed that most de novo IPD patients were included in the normal average range of respiratory and phonatory ability. But the respiratory and phonatory ability of de novo IPD patients showed lower tendency as compared with the normal group. When the average of respiratory and phonatory ability among the gender was compared, the difference of males was greater than the difference of females.

• Molecules and Cells
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• v.40 no.7
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• pp.450-456
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• 2017

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-$erb{\alpha}$ induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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• pp.171-174
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• 2007

Neuronal death is a common characteristic hallmark of a variety of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. However, there have been no effective drugs to successfully prevent neuronal death in those diseases, whereas oriental medicinal plants have to possess valuable therapeutic potentials to treat neurodegenerative diseases. In the present study, in an attempt to provide neuroprotective agents from natural plants, 80% methanol extracts of a wide range of medicinal plants, which are native to Jeju Island in Korea, were prepared and their protective effects on hydrogen peroxide-induced apoptotic cell death were examined. Among those tested, extracts from Smilax china and Saururus chinesis significantly decreased hydrogen peroxide-induced apoptotic cell death. The extracts attenuated hydrogen peroxide($H_2O_2$)-induced caspase-3 activation in a dose-dependent manner. Further, plant extracts restored $H_2O_2$-induced depletion of intracellular glutathione, a major endogenous antioxidant. The data suggest that Jeju native medicinal plants could potentially be used as therapeutic agents for treating or preventing neurodegenerative diseases in which oxidative stress is implicated.

• Molecules and Cells
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• v.37 no.3
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• pp.226-233
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• 2014

Excessive reactive oxygen species (ROS) generated from abnormal cellular process lead to various human diseases such as inflammation, ischemia, and Parkinson's disease (PD). Sensitive to apoptosis gene (SAG), a RING-FINGER protein, has anti-apoptotic activity and anti-oxidant activity. In this study, we investigate whether Tat-SAG, fused with a Tat domain, could protect SH-SY5Y neuroblastoma cells against 1-methyl-4-phenylpyridinium ($MPP^+$) and dopaminergic (DA) neurons in the substantia nigra (SN) against 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) toxicity. Western blot and immunohistochemical analysis showed that, unlike SAG, Tat-SAG transduced efficiently into SH-SY5Y cells and into the brain, respectively. Tat-SAG remarkably suppressed ROS generation, DNA damage, and the progression of apoptosis, caused by $MPP^+$ in SH-SY5Y cells. Also, immunohistochemical data using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that Tat-SAG obviously protected DA neurons in the SN against MPTP toxicity in a PD mouse model. Tat-SAG-treated mice showed significant enhanced motor activities, compared to SAG- or Tat-treated mice. Therefore, our results suggest that Tat-SAG has potential as a therapeutic agent against ROS-related diseases such as PD.

• Health Policy and Management
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• v.33 no.2
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• pp.129-140
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• 2023

Background: This study aims to compare the burden of disease in Korea with other Organization for Economic Cooperation and Development (OECD) countries using the OECD health statistics from 1985 to 2020. Methods: We analyzed potential years of life lost (YLL) per 100,000 population using the Positive value for relative comparison (PARC) index, trend test, and average annual percentage change (AAPC) with logistic regression analysis. Results: The relative disease burden was good for many diseases, but the disease burden was severe for a few diseases in Korea. Diseases with a high relative burden of disease in Korea are as follows; intentional self-harm (YLL2020 575.6, AAPCYLL 2.6%; PARC2020 -1.000, AAPCPARC -15.8%), malignant neoplasms of the liver (YLL2020 136.6, AAPCYLL -3.9%; PARC2020 -1.000, AAPCPARC 0.0%), malignant neoplasms of the stomach (YLL2020 9.0, AAPCYLL 3.2%; PARC2020 -0.556, AAPCPARC -22.9%), Parkinson's disease (YLL2020 575.6, AAPCYLL 2.6%; PARC2020 -1.000, AAPCPARC -15.8%). Conclusion: Diseases with a high burden of disease are needed to be prioritized in the planning and execution of healthcare policies that can contribute to the efficient use of healthcare resources.

• Journal of Korean Neurosurgical Society
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• v.30 no.6
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• pp.688-698
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• 2001

Objectives : Parkinson's disease is a well-known neurodegenerative disease characterized by dopaminergic cell death in the substantia nigra. The reactive gliosis by activated astrocytes and microglias is no more regarded as a simple sequel of neuronal cell death. Microglial activation takes place in a stereotypic pattern with graded morphologic and functional(resting, activated and phagocytic) changes. In Parkinson's disease animal model, the degree of microglial activation along the nigro-striatal dopaminergic tract has not been studied intensively. The purpose of this study was to elucidate the characteristics of microglial reaction and to grade its degree of activation at substantia nigra and corpus striatum using 6-hydroxydopamine induced rat model of Parkinson's disease. Methods : Using Sprague-Dawley rat, parkinsonian model was made by 6-hydroxydopamine(OHDA) induced destruction of medial and lateral substantia nigra(SN). The rat was sacrificed 3-, 5-, 7-, 14- and 21-day-after operation. For control group, we injected saline with same manner and sacrificed 3-day after operation. With immunohistochemistry, we examined dopaminergic neuronal cells and microglial expression using tyrosine hydroxylase (TH) and OX-42 antibodies, respectively. Also we performed in situ hybridization for osteopontin, a possible marker of subset in activated microglia. Results : 1) In lesioned side of substantia nigra and corpus striatum, the TH immunoreactivity was markedly decreased in whole experimental groups. 2) Using optical densitometry, microglia induced immunoreactivity of OX-42 was counted at SN and corpus striatum. At SN, it was increased significantly on the lesioned side in control and all time-dependent experimental groups. At striatum, it was increased significantly in post lesion 3-day group only(p <0.05). Compared to control group, immunoreactivity of OX-42 on lesioned side was increased in groups, except post lesion 21-day group, at SN. Only post lesion 3-day group showed significance at striatum(p <0.05). Compared to SN region, immunoreactivity of OX-42 was much weaker in striatum. 3) Microscopically, the microglias showed typically different activation pattern. At SN, numerous phagocytic microglias were found at pars compacta and reticularis of lesion side. At striatum, no phagocytic form was found and the intensity of staining was much weaker. 4) At SN, the immunoreactivity of osteopontin showed definite laterality and it was markedly increased at pars compacta of lesion side with relatively short duration time. At striatum, however, it was not detected by in situ hybridization technique. Conclusion : The nigral 6-OHDA induced rat model of Parkinson's disease revealed several characteristic patterns of microglial reaction. At SN, microglias was activated shortly after direct neuronal damage and maintained for about three weeks. In contrast, despite of sufficient dopaminergic insufficiency at striatum, activation of microglias was trivial, and distinguished 3 day later. Antegrade slow neuronal degeneration is major pathophysiology in striatal dopaminergic deficiency. So, the acuteness of neuronal damage and consequential degree of neuronal degeneration may be important factor for microglial activation in neurodegenerative diseases such as Parkinson's disease. Additionally, osteopontin may be a possible marker for several subsets of activated microglia, possibly the phagocytic form.

• Journal of Korean Neurosurgical Society
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• v.30 no.3
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• pp.342-348
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• 2001

Objective : Dopamine transporter concentrations have been known to decrease in Parkinson's disease(PD). The aim of the present study was to evaluate the correlation between SPECT measurements of [I-123]N-(3-iodopropene-2-yl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-chlorophenyl) tropane(IPT) as an imaging agent for measuring changes in transporter concentrations with PD. Patients and Methods : IPT labelled with $4.87{\pm}1.29mCi$($180.19{\pm}47.73MBq$) of [I-123] was intravenously injected into 23 patients(age : $58{\pm}12$) with PD and three normal controls(NC)(age : $37{\pm}7$) as bolus. Brain SPECT were then performed at 1 hour and 2 hours after injection on a double headed camera. The statistical parameters were the contrast ratio of left basal ganglia(BG) and right basal ganglia to occipital cortex(OCC) per milli curies of injected radiotracer at 1 hour and 2 hours. The correlations were evaluated between these parameters and Hoehn-Yahr classification of the patients. Results : The(BG - OCC)/OCC/mCi ratios at 1 hour and 2 hours for PD and NC were $0.14{\pm}0.07$ and $0.27{\pm}0.07$(1 hour) and $0.12{\pm}0.07$ and $0.34{\pm}0.04$(2 hour), respectively. The(BG - OCC)/OCC/mCi ratios of Parkinson's disease were decreased with higher grade of Hoehn-Yahr classification of the patients. The ratio between BG and OCC for PD were clearly separated from NC and may be useful outcome measures for clinical diagnosis. Conclusion : The findings suggest that IPT may be a very useful tracer for early diagnosis and treatment of PD and study of dopamine re-uptake site.

• Journal of Dental Rehabilitation and Applied Science
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• v.32 no.4
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• pp.301-306
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• 2016

It is very hard for edentulous patients to satisfy retention and stability with their complete denture. Especially, for patients with systemic diseases such as Parkinson's disease causing involuntary and limited movements, fabricating complete dentures may be challenging to both dentists and patients due to functional limitations. To overcome this problem, overdentures can be used through conserving retained roots. In this case, a 45-year-old male patient had to extract numerous teeth due to dental caries, and at the time of visit he was taking drugs for diabetes and Parkinson's disease for a period of long time. A complete denture was applied to maxilla, and for mandible, an overdenture on two preserved retained roots was applied where its retention and stability were obtained by magnetic attachments. This case reports that overdenture with retained roots improved overall functional limitations.

• Korean Journal of Community Nutrition
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• v.13 no.4
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• pp.582-591
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• 2008

Both genetic and environmental factors play important roles in the pathogenesis of Parkinson Disease(PD). The contribution of many environmental factors including dietary factor remains unproven. The purpose the study was to investigate the dietary habits, nutrient intake and dietary quality of Korean PD patients according to the duration of disease. PD patients were recruited from K and S university hospitals from May 2005 to January 2006. This study was carried out after approval by the Institute Review Board(IRB). British Brain Bank criteria was used to diagnose PD. The subjects were classified into 2 groups based on the duration of PD: <25 months and $\geq$25 months groups. General characteristics, anthropometric measurements, food habits and dietary intakes were investigated. The results of this study were as follows: 1) The mean age of <25 months group($66.9{\pm}8.0$ yr) was significantly higher than that of $\geq$25 months group($62.2{\pm}8.8$ yr)(p<0.05). No significant differences were found for academic background, occupation, living status and social activity, however, numbers of diseases, exercise and family history of PD were significantly different. 2) Anthropometric measurements were not different between the two groups. 3) The frequency of taking snacks was significantly higher in <25 months group and the amounts of alcohol consumption were significantly higher in $\geq$25 months group. 4) Daily intakes of most nutrients were very low compared with DRI. 5) The MAR score was significantly lower in <25 months group(p<0.05;) however, the scores of DVS, DDS and DQI were not significantly different. As a conclusion an overall nutrient intake and dietary quality of the Parkinson's Disease patients need to be improved regardless of duration of the disease and a well-balanced diet should be emphasized.