• The Journal of Korea Assosiation for Disability and Oral Health
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• v.15 no.1
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• pp.40-44
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• 2019

Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease of unknown etiology characterized by progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. The clinical presentations of MMD include transient ischemic attacks (TIA), ischemic stroke, hemorrhagic stroke, seizures, headache, and cognitive impairment. MMD is the most important cause of stroke or TIA in children in East Asian countries. A 5-year-3-month old boy with MMD experienced cerebral infarctions five times. Cerebrovascular anastomosis surgery was performed on him four years ago. He had dysphagia, developmental delay, hemiplegia, and strabismus. Besides, a number of dental caries in primary dentition were identified during clinical oral examination. Dental treatment under general anesthesia using sevoflurane was performed due to his lack of cooperation and underlying systemic disease. MMD is associated with various medical diseases requiring thoughtful consideration during dental treatment. Crying and hyperventilation in MMD patients may cause hypocapnia and have a cerebral vasoconstrictive effect. If dental treatment is required, control of pain and anxiety is very important. General anesthesia may be considered for dental treatment in uncooperative or very young patients with MMD.

• Journal of Life Science
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• v.29 no.8
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• pp.846-853
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• 2019

Phytochemical compounds of Ligusticum striatum Makino are used as traditional medicinal herbs in Asia. These compounds are reported to have pain relief and antioxidant activities in gynecological and brain diseases. In this study, we investigated the antioxidant effects of Ligusticum fermented ethanol extract from Lactobacillus plantarum BHN-LAB 129 isolated from Kimchi, a Korean traditional food. The total polyphenol and total flavonoid contents increased by about 116.2% and 281.0% respectively, in the fermented Ligusticum extract as compared with those in the nonfermented Ligusticum ethanol extract. Superoxide dismutase-like (SOD), DPPH radical scavenging, ABTS radical scavenging, and reducing power activities increased by around 139.9%, 199.6%, 301.0%, and 137.1%, respectively, in the fermented Ligusticum ethanol extract as compared with these parameters in the nonfermented Ligusticum ethanol extract, respectively. In conclusion, the fermented Ligusticum ethanol extract with L. plantarum BHN-LAB 129 was effective in increasing the antioxidant effects. The bioconversion process in this study points to the potential of using Ligusticum to produce phytochemical-enriched natural antioxidant agents with high added value. The findings may prove useful in the development of improved foods and cosmetic materials.

• Molecules and Cells
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• v.42 no.6
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• pp.480-494
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• 2019

Aggregates of disease-causing proteins dysregulate cellular functions, thereby causing neuronal cell loss in diverse neurodegenerative diseases. Although many in vitro or in vivo studies of protein aggregate inhibitors have been performed, a therapeutic strategy to control aggregate toxicity has not been earnestly pursued, partly due to the limitations of available aggregate models. In this study, we established a tetracycline (Tet)-inducible nuclear aggregate (${\beta}23$) expression model to screen potential lead compounds inhibiting ${\beta}23$-induced toxicity. High-throughput screening identified several natural compounds as nuclear ${\beta}23$ inhibitors, including peucedanocoumarin III (PCIII). Interestingly, PCIII accelerates disaggregation and proteasomal clearance of both nuclear and cytosolic ${\beta}23$ aggregates and protects SH-SY5Y cells from toxicity induced by ${\beta}23$ expression. Of translational relevance, PCIII disassembled fibrils and enhanced clearance of cytosolic and nuclear protein aggregates in cellular models of huntingtin and ${\alpha}$-synuclein aggregation. Moreover, cellular toxicity was diminished with PCIII treatment for polyglutamine (PolyQ)-huntingtin expression and ${\alpha}$-synuclein expression in conjunction with 6-hydroxydopamine (6-OHDA) treatment. Importantly, PCIII not only inhibited ${\alpha}$-synuclein aggregation but also disaggregated preformed ${\alpha}$-synuclein fibrils in vitro. Taken together, our results suggest that a Tet-Off ${\beta}23$ cell model could serve as a robust platform for screening effective lead compounds inhibiting nuclear or cytosolic protein aggregates. Brain-permeable PCIII or its derivatives could be beneficial for eliminating established protein aggregates.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.317-328
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• 2018

Cognitive impairment responses are important research topics in the study of degenerative brain diseases as well as in understanding of human mental activities. To compare response to scopolamine (SPL)-induced cognitive impairment, we measured altered parameters for learning and memory ability, inflammatory response, oxidative stress, cholinergic dysfunction and neuronal cell damages, in Korl:ICR stock and two commercial breeder stocks (A:ICR and B:ICR) after relevant SPL exposure. In the water maze test, Korl:ICR showed no significant difference in SPL-induced learning and memory impairment compared to the two different ICRs, although escape latency was increased after SPL exposure. Although behavioral assessment using the manual avoidance test revealed reduced latency in all ICR mice after SPL treatment as compared to Vehicle, no differences were observed between the three ICR stocks. To determine cholinergic dysfunction induction by SPL exposure, activity of acetylcholinesterase (AChE) assessed in the three ICR stocks revealed no difference of acetylcholinesterase activity. Furthermore, low levels of superoxide dismutase (SOD) activity and high levels of inflammatory cytokines in SPL-treated group were maintained in all three ICR stocks, although some variations were observed between the SPL-treated groups. Neuronal cell damages induced by SPL showed similar response in all three ICR stocks, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Nissl staining analysis and expression analyses of apoptosis-related proteins. Thus, the results of this study provide strong evidence that Korl:ICR is similar to the other two ICR. Stocks in response to learning and memory capacity.

• Journal of Life Science
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• v.31 no.2
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• pp.237-247
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• 2021

Immune responses in the central nervous system (CNS) function as the host's defense system against pathogens and usually help with repair and regeneration. However, chronic and exaggerated neuroinflammation is detrimental and may create neuronal damage in many cases. The NOD-, LRR-, and pyrin domain―containing 3 (NLRP3) inflammasome, a kind of NOD-like receptor, is a cytosolic multiprotein complex that consists of sensors (NLRP3), adaptors (apoptosis-associated speck like protein containing a caspase recruitment domain, ASC) and effectors (caspase 1). It can detect a broad range of microbial pathogens along with foreign and host-derived danger signals, resulting in the assembly and activation of the NLRP3 inflammasome. Upon activation, NLRP3 inflammasome leads to caspase 1-dependent secretion of the pro-inflammatory cytokines IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. NLRP3 inflammasome is highly expressed in CNS-resident cell types, including microglia and astrocytes, and growing evidence suggests that NLRP3 inflammasome is a crucial player in the pathophysiology of several neuroinflammatory and psychiatric diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and major depressive disorder. Thus, this review describes the molecular mechanisms of NLRP3 inflammasome activation and its crucial roles in the pathogenesis of neurological disorders.

• Journal of Korean Neurosurgical Society
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• v.64 no.4
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• pp.644-664
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• 2021

Objective : Since the enactment of the Special Act on Korean Medical Residents, neurosurgeons working at training hospitals have been performing the duties of residents, in addition to their existing patient care responsibilities, which include surgery, education, and research. This study explores the relationships between work intensity, work-life balance, and burnout experienced by Korean neurosurgeons. Methods : The participants (n=451) were neurosurgeons working at training hospitals throughout Republic of Korea. Data on socio-demographic characteristics (including objective and subjective work environment), work intensity, work-life balance, and burnout were gathered using self-report questionnaires completed between March 1 and December 20, 2019. The data were analyzed using descriptive statistics, independent samples t-tests, one-way analysis of variance, Pearson's correlations, and multiple regression analysis. IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, NY, USA) was used for the analyses. Results : The work intensity, work-life balance, and burnout levels of neurosurgeons were 3.95, 3.57 (on a scale from 1 to 5) and 4.60 (on a scale from 1 to 7); and 280 (62.1%) of 451 neurosurgeons were found to be experiencing burnout. By controlling for the socio-demographic characteristics, the effects of work intensity and work-life balance on burnout were analyzed. Work intensity (B=0.314), work-life balance-family and leisure (B=0.216), work-life balance-growth (B=0.147), job stress (B=0.133), and satisfaction with human relationships (B=-0.069) were shown to be significant (all p<0.05), and they were found to affect burnout in the abovementioned order. The overall explanatory power was 58.3% (p<0.05), and the explanatory power with the addition of independent variables such as work intensity and work-life balance was 14.5% (p<0.05). Conclusion : This study showed that Korean neurosurgeons working at training hospitals experienced a high level of work intensity and job stress, and low work-life balance. Additionally, nearly half of the neurosurgeons were found to experience burnout related to factors such as work intensity, work-life balance, job stress, and satisfaction with human relationships. In particular, these factors seem to have deteriorated further after the implementation of the Special Act on Korean Medical Residents. These very high levels of burnout among Korean neurosurgeons who care for patients with both brain and spinal diseases may have a very important impact on patients' health. Therefore, it is recommended that the Korean Neurosurgical Society and the Korean government make efforts to improve the factors that affect burnout among Korean neurosurgeons.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.515-525
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• 2022

Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca²⁺]_i. The open-field test and poleclimbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca²⁺]_i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.750-758
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• 2022

Background: Mild cognitive impairment (MCI) is a transitional condition between normality and dementia. Ginseng is known to have effects on attenuating cognitive deficits in neurogenerative diseases. Ginsenosides are the main bioactive component of ginseng, and their protein targets have not been fully understood. Furthermore, no thorough analysis is reported in ginsenoside-related protein targets in MCI. Methods: The candidate protein targets of ginsenosides in brain tissues were identified by drug affinity responsive target stability (DARTS) coupled with label-free liquid chromatography-mass spectrometry (LC-MS) analysis. Network pharmacology approach was used to collect the therapeutic targets for MCI. Based on the above-mentioned overlapping targets, we built up a proteineprotein interaction (PPI) network in STRING database and conducted gene ontology (GO) enrichment analysis. Finally, we assessed the effects of ginseng total saponins (GTS) and different ginsenosides on mitochondrial function by measuring the activity of the mitochondrial respiratory chain complex and performing molecular docking. Results: We screened 2526 MCI-related protein targets by databases and 349 ginsenoside-related protein targets by DARTS. On the basis of these 81 overlapping genes, enrichment analysis showed the mitochondria played an important role in GTS-mediated MCI pharmacological process. Mitochondrial function analysis showed GTS, protopanaxatriol (PPT), and Rd increased the activities of complex I in a dose-dependent manner. Molecular docking also predicted the docking pockets between PPT or Rd and mitochondrial respiratory chain complex I. Conclusion: This study indicated that ginsenosides might alleviate MCI by targeting respiratory chain complex I and regulating mitochondrial function, supporting ginseng's therapeutic application in cognitive deficits.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.3
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• pp.205-216
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• 2022

Background: People with special needs tend to require diverse behavioral management in dentistry. They may feel anxious or uncomfortable or may not respond to any communication with the dentists. Patients with medical, physical, or psychological disorders may not cooperate and therefore require sedation (SED) or general anesthesia (GA) to receive dental treatment. Using the healthcare big data in Korea, this study aimed to analyze the trends of SED and GA in special needs patients undergoing dental treatment. It is believed that these data can be used as reference material for hospitals and for preparation of guidelines and related policy decisions of associations or governments for special needs patients in dentistry. Methods: The study used selected health information data provided by the Korean National Health Insurance Service. Patients with a record of use of one of the eight selected drugs used in dental SED between January 2007 and September 2019, those with International Classification of Diseases-10 codes for attention deficit hyperactivity disorder (ADHD), phobia, brain disease, cerebral palsy, epilepsy, genetic disease, autism, mental disorder, mental retardation, and dementia were selected. The insurance claims data were analyzed for age, sex, sedative use, GA, year, and institution. Results: The number of special needs patients who received dental treatment under SED or GA from January 2007 to September 2019 was 116,623. Number of SED cases was 136,018, performed on 69,265 patients, and the number of GA cases was 56,308, implemented on 47,257 patients. In 2007, 3100 special needs patients received dental treatment under SED while in 2018 the number of cases increased 6 times to 18,528 SED cases. In dentistry, ADHD was the most common disability for SED cases while phobia was the most common cause of disability for GA. The male-to-female ratio with respect to SED cases was higher for males (M : F = 64.36% : 35.64%). Conclusion: The application of the SED method and GA for patients with special needs in dentistry is increasing rapidly; thus, preparing guidelines and reinforcing the education and system are necessary.

• Journal of Life Science
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• v.33 no.3
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• pp.287-294
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• 2023

Healthy adipose tissue is critical for preventing obesity by maintaining metabolic homeostasis. Adipose tissue plays an important role in energy homeostasis through glucose and lipid metabolism. Depending on nutritional status, adipose tissue expands to store lipids or can be consumed by lipolysis. The role of adipose tissue as an endocrine organ is emerging, and many studies have reported that there are various adipose tissue hormones that communicate with other organs and tissues through metabolic signaling. For example, leptin, a representative peptide hormone secreted from adipose tissues (adipokine), circulates and targets the central nervous system of the brain for appetite regression. Furthermore, adipocytes secrete inflammatory cytokines to target immune cells in adipose tissues. Not surprisingly, adipocytes can secrete fatty acid-derived hormones (lipokine) that bind to their specific receptors for paracrine and endocrine action. To understand organ crosstalk by adipose tissue hor- mones, specific metabolic signaling in adipocytes and other communicating cells should be defined. The dysfunction of metabolic signaling in adipocytes occurs in unhealthy adipose tissue in overweight and obese conditions. Therapy targeting novel adipose metabolic signaling could potentially lead to the development of an effective anti-obesity drug. This review summarizes the latest updates on adipose tissue hormone and metabolic signaling in terms of obesity and metabolic diseases.