• Korean Journal of Radiology
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• 제24권3호
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• pp.247-258
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• 2023

Objective: To localize the neuroanatomical substrate of rapid eye movement sleep behavior disorder (RBD) and to investigate the neuroanatomical locational relationship between RBD and α-synucleinopathy neurodegenerative diseases. Materials and Methods: Using a systematic PubMed search, we identified 19 patients with lesions in different brain regions that caused RBD. First, lesion network mapping was applied to confirm whether the lesion locations causing RBD corresponded to a common brain network. Second, the literature-based RBD lesion network map was validated using neuroimaging findings and locations of brain pathologies at post-mortem in patients with idiopathic RBD (iRBD) who were identified by independent systematic literature search using PubMed. Finally, we assessed the locational relationship between the sites of pathological alterations at the preclinical stage in α-synucleinopathy neurodegenerative diseases and the brain network for RBD. Results: The lesion network mapping showed lesions causing RBD to be localized to a common brain network defined by connectivity to the pons (including the locus coeruleus, dorsal raphe nucleus, central superior nucleus, and ventrolateral periaqueductal gray), regardless of the lesion location. The positive regions in the pons were replicated by the neuroimaging findings in an independent group of patients with iRBD and it coincided with the reported pathological alterations at post-mortem in patients with iRBD. Furthermore, all brain pathological sites at preclinical stages (Braak stages 1-2) in Parkinson's disease (PD) and at brainstem Lewy body disease in dementia with Lewy bodies (DLB) were involved in the brain network identified for RBD. Conclusion: The brain network defined by connectivity to positive pons regions might be the regulatory network loop inducing RBD in humans. In addition, our results suggested that the underlying cause of high phenoconversion rate from iRBD to neurodegenerative α-synucleinopathy might be pathological changes in the preclinical stage of α-synucleinopathy located at the regulatory network loop of RBD.

• 음성과학
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• 제12권3호
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• pp.19-33
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• 2005

Tremor is a main factor of parkinsonism. Voice tremor may be the first, later or the only symptom of a neurological disease and its frequency, amplitude, and regularity may differ among the diseases of different neural subsystems. Differential diagnosis between idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA) has been difficult. This study included three groups: (1) 6 IPD patients; (2) 6 MSA patients; and (3) 20 ageand sex-matched normal controls. The MDVP (Multidimensional Voice Program) was used to analyze the sustained /a/phonation. The results were as follows: (1) frequency perturbation parameters (jitter, sPPQ, Vf0) and FTRI of tremor parameter of two patient groups were statistically different from those of the controls (p < .01); (2) measures were higher in short-term and long-term f0 and amplitude perturbation in MSA than IPD; (3) however, any acoustic parameters between IPD and MSA were not statistically different; except for the rate of frequency tremor, 4$\sim$5 Hz in IPD, 5$\sim$11 Hz in MSA and (4) the pattern of regularity for voice tremor through histogram indicated that amplitude of IPD was irregular while both f0 and amplitude of MSA were irregular. In conclusion, F0, rate of frequency tremor, and pattern of f0 regularity may be predictors for differential diagnosis. These findings might signify that voice tremor of parkinsonism was resulted from modulation of f0.

• Journal of Korean Neurosurgical Society
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• 제62권1호
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• pp.10-26
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• 2019

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer's disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

• Biomolecules & Therapeutics
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• 제31권3호
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• pp.276-284
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• 2023

Sinapic acid (SA) is a phenolic acid that is widely distributed in fruits and vegetables, which has various bioactivities, such as antidiabetic, anticancer and anti-inflammatory functions. Over-activated microglial is involved in the development progress of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. The objective of this study was to investigate the effect of SA in microglia neuroinflammation models. Our results demonstrated that SA inhibited secretion of the nitric oxide (NO) and interleukin (IL)-6, reduced the expression of inducible nitric oxide synthase (iNOS) and enhanced the release of IL-10 in a dose-dependent manner. Besides, our further investigation revealed that SA attenuated the phosphorylation of AKT and MAPK cascades in LPS-induced microglia. Consistently, oral administration of SA in mouse regulated the production of inflammation-related cytokines and also suppressed the phosphorylation of MAPK cascades and AKT in the mouse cerebral cortex. These results suggested that SA may be a possible therapy candidate for anti-inflammatory activity by targeting the AKT/MAPK signaling pathway.

• 대한방사성의약품학회지
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• 제8권1호
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• pp.3-8
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• 2022

Alteration of the mGluR5 density is closely related to various brain diseases including schizophrenia, depression, Parkinson's disease, and Alzheimer's disease. Therefore, mGluR5 is considered as a valuable imaging biomarker for brain disease and many radiopharmaceuticals have been developed so far. Among them, [¹⁸F]FPEB has favorable pharmacokinetic characteristics, and this is the most frequently used radiopharmaceutical for preclinical and clinical studies. In the present study, we want to introduce the optimized radiosynthetic method for the routine production of [¹⁸F]FPEB using a GE TRACERlabTM FXFN pro module. In addition, the entire process was monitored with a webcam to solve the problems arising from the synthetic process. As a result, [¹⁸F]FPEB was prepared by nucleophilic substitution from its nitro- precursor at 120℃ for 20 min in dimethyl sulfoxide. Radiochemical yield was 13.7 ± 5.1% (decay-corrected, n = 91) with the molar activity of 84 ± 17 GBq/µmol at the end of synthesis. The radiochemical purity was determined to be above 96%. The manufactured [¹⁸F]FPEB injection for quality controls were carried out in accordance with an KIRAMS approved protocol, as per ICH and USP guidelines.

• International Journal of Industrial Entomology and Biomaterials
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• 제48권2호
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• pp.59-66
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• 2024

The mature Bombyx mori silkworm is recognized as a rich source of several nutrients. A unique steaming process has been developed to enhance the palatability of Bombyx mori silkworm and make it more convenient to consume. Additionally, it has also been freeze-dried into a powder form, which is recognized as a nutritional supplement with many health benefits. Steamed and Freeze-dried Mature Silkworm Powder (SMSP) is said to offer a wide range of benefits, including longevity, improved athletic performance, prevention of alcohol-induced liver fibrosis or tumors, amelioration of fatty liver, prevention of peptic ulcers, regulation of melanin production, and mitigation of Parkinson's and Alzheimer's diseases by improving cognitive function. The nutritional composition of SMSP is particularly high in glycine, alanine and serine. This review aims to summarize the molecular mechanisms underlying the diverse effects induced by these key components of SMSP. Such elucidation will enhance the credibility of future studies on SMSP, which will require more comprehensive analyses. It appears that SMSP represents a natural health supplement that could have a positive impact on global human health while increasing income.

• Molecules and Cells
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• 제40권4호
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• pp.280-290
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• 2017

Several lines of evidence suggest that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Protein tyrosine phosphatase 1B (PTP1B) is known to regulate the ER stress signaling pathway, but its role in neuronal systems in terms of ER stress remains largely unknown. Here, we showed that rotenone-induced toxicity in human neuroblastoma cell lines and mouse primary cortical neurons was ameliorated by PTP1B inhibition. Moreover, the increase in the level of ER stress markers ($eIF2{\alpha}$ phosphorylation and PERK phosphorylation) induced by rotenone treatment was obviously suppressed by concomitant PTP1B inhibition. However, the rotenone-induced production of reactive oxygen species (ROS) was not affected by PTP1B inhibition, suggesting that the neuroprotective effect of the PTP1B inhibitor is not associated with ROS production. Moreover, we found that MG132-induced toxicity involving proteasome inhibition was also ameliorated by PTP1B inhibition in a human neuroblastoma cell line and mouse primary cortical neurons. Consistently, downregulation of the PTP1B homologue gene in Drosophila mitigated rotenone- and MG132-induced toxicity. Taken together, these findings indicate that PTP1B inhibition may represent a novel therapeutic approach for ER stress-mediated neurodegenerative diseases.

• 동의생리병리학회지
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• 제25권4호
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• pp.628-634
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• 2011

The roots of Polygala tenuifolia Willd. is a well-known traditional medicine used as expectorant, tonic, tranquilizer in Asia including China and Korea. And also have been used to treat amnesia, neurasthenia, palpitation, insomnia, and disorientation. Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as Parkinson's disease, Alzheimer's disease, epilepsy and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a role in the pathogenesis of these diseases. NNMBS269, acid hydrolysis EtOAc fraction of the P. tenuifolia showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells while general EtOAc fraction of the P. tenuifolia (NNMBS268) not shown. NNMBS269 induced the expression of HO-1 protein that has been proposed to play an important cellular defense role against oxidant injury. In addition increased HO activity. In mouse hippocampal HT22 cells, NNMBS269 makes the nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2). In conclusion, acid hydrolysis EtOAc fraction the P. enuifolia. (NNMBS269) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 translocation in mouse hippocampal HT22 cells.

• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.307-319
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• 2021

Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson's disease, Alzheimer's disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

• 대한약침학회지
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• 제26권1호
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• pp.60-66
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• 2023

Objectives: Discussions regarding "medical blind spots" in Korea's "aging society" are continuously rising. In addition, the demand for medical attention and care for the elderly and vulnerable populations continues to increase. Given this, the government is promoting the "home healthcare service" project. This study aims to lay the foundation for promoting this project by investigating the perception of clinical Korean Medicine (KM) doctors in the "community health care" project. Methods: With the cooperation of the Association of Korean Medicine, we sent a questionnaire to all KM doctors through e-mail. The survey included personal information, awareness, appropriate disease and intervention, proper visit location, and pros and cons. Results: A total of 602 responses were collected and analyzed. Approximately 20% of the doctors answered that they were well aware of the service, while 55% responded that they did not know about it. For a visit, a KM doctor selected the appropriate diseases in the order of stroke, dementia and Parkinson's disease, osteoarthritis, and chronic diseases. Among treatments, acupuncture, moxibustion, and herbal medicine exhibited similar results. The most common opinion was that KM doctors should schedule their visits once a week for 6-12 months, which was the most prolonged period among the given options. More than 80% (84.1%) of the doctors replied that care projects were highly essential, and about 63.8% expressed their willingness to participate in these projects. Conclusion: To provide appropriate home health care, we must raise awareness among Korean medicine doctors. In addition, the healthcare budget must be increased to provide the required support.