• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.455-464
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• 2022

Efonidipine, a calcium channel blocker, is widely used for the treatment of hypertension and cardiovascular diseases. In our preliminary study using structure-based virtual screening, efonidipine was identified as a potential inhibitor of c-Jun N-terminal kinase 3 (JNK3). Although its antihypertensive effect is widely known, the role of efonidipine in the central nervous system has remained elusive. The present study investigated the effects of efonidipine on the inflammation and cell migration induced by lipopolysaccharide (LPS) using murine BV2 and human HMC3 microglial cell lines and elucidated signaling molecules mediating its effects. We found that the phosphorylations of JNK and its downstream molecule c-Jun in LPS-treated BV2 cells were declined by efonidipine, confirming the finding from virtual screening. In addition, efonidipine inhibited the LPS-induced production of pro-inflammatory factors, including interleukin-1β (IL-1β) and nitric oxide. Similarly, the IL-1β production in LPS-treated HMC3 cells was also inhibited by efonidipine. Efonidipine markedly impeded cell migration stimulated by LPS in both cells. Furthermore, it inhibited the phosphorylation of inhibitor kappa B, thereby suppressing nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 cells. Taken together, efonidipine exerts anti-inflammatory and anti-migratory effects in LPS-treated microglial cells through inhibition of the JNK/NF-κB pathway. These findings imply that efonidipine may be a potential candidate for drug repositioning, with beneficial impacts on brain disorders associated with neuroinflammation.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.285-297
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• 2023

Alzheimer's disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. To expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

• Journal of Korean Academy of Nursing
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• v.53 no.4
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• pp.371-384
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• 2023

Purpose: With an increase in the aging population, the number of patients with degenerative spinal diseases undergoing surgery has risen, as has the incidence of postoperative delirium. This study aimed to investigate the risk factors affecting postoperative delirium in older adults who had undergone spine surgery and to identify the associated biomarkers. Methods: This study is a prospective study. Data of 100 patients aged ≥ 70 years who underwent spinal surgery were analyzed. Demographic data, medical history, clinical characteristics, cognitive function, depression symptoms, functional status, frailty, and nutritional status were investigated to identify the risk factors for delirium. The Confusion Assessment Method, Delirium Rating Scale-R-98, and Nursing Delirium Scale were also used for diagnosing delirium. To discover the biomarkers, urine extracellular vesicles (EVs) were analyzed for tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light, and glial fibrillary acidic protein using digital immunoassay technology. Results: Nine patients were excluded, and data obtained from the remaining 91 were analyzed. Among them, 18 (19.8%) developed delirium. Differences were observed between participants with and without delirium in the contexts of a history of mental disorder and use of benzodiazepines (p = .005 and p = .026, respectively). Tau and UCH-L1-concentrations of urine EVs-were comparatively higher in participants with severe delirium than that in participants without delirium (p = .002 and p = .001, respectively). Conclusion: These findings can assist clinicians in accurately identifying the risk factors before surgery, classifying high-risk patients, and predicting and detecting delirium in older patients. Moreover, urine EV analysis revealed that postoperative delirium following spinal surgery is most likely associated with brain damage.

• Pediatric Infection and Vaccine
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• v.30 no.2
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• pp.91-96
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• 2023

Infection with enterovirus (EV) 71 is usually associated with hand-foot-and-mouth disease and herpangina. The most frequent neurologic complication is brainstem encephalitis. A 30-month-old boy visited the pediatric emergency department with fever, lethargy, and abnormal eye contact. His mental status was slightly drowsy. On hospitalization day 2, the patient experienced respiratory arrest with apnea. Brain magnetic resonance imaging revealed bilateral symmetric T2-high signal lesions without enhancement in the posterior aspect of the brainstem and left medial temporal lobe. Electroencephalography was indicative of diffuse cerebral dysfunction with diffuse high amplitude and irregular delta activities. He underwent a gene study and was diagnosed with myoclonic epilepsy with ragged red fibers syndrome. We report a case of EV 71 brainstem encephalitis by polymerase chain reaction for nasopharyngeal aspirates and feces with rapid progression within one day of fever without the manifestation of throat and skin lesions because of his underlying mitochondrial disease.

• The Korea Journal of Herbology
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• v.24 no.4
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• pp.173-179
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• 2009

Objectives : In this study, the effects of different fractions isolated from modified Boyanghwanotang(mBHT) extract on LPS-induced inflammation in BV2 microglial cells were investigated. Methods : mBHT was extracted with water, and then fractionated with n-hexane, methylene chloride, ethylacetate and n-butanol. BV2 cells, a mouse microglia line were incubated with different concentrations of each fraction of mBHT for 30 min, and then stimulated with LPS for 24 h. Cell toxicity was determined by MTT assay. The concentration of nitric oxide (NO) was measured in culture medium by Griess reagent assay. The expression of inducible nitric oxide synthease (iNOS) protein was determined by Western blot. Results : Four fractions of mBHT were significantly inhibited LPS-induced NO productions in BV2 cells in a dose-dependent manner. The methylene chloride fraction of mBHT was most strongly inhibited the NO production compared with those of the others. The methylene chloride fraction of mBHT was also suppressed LPS-induced iNOS expression comparison of other fractions at same concentration ($50\;{\mu}g/ml$) in BV2 cells. Conclusions : The results showed that the methylene chloride fraction of mBHT may have an strong anti-inflammatory property through the inhibition of NO production and iNOS expression in activated microglia, and could a therapeutic potential for the treatment of various brain inflammatory diseases.

• Journal of dental hygiene science
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• v.23 no.3
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• pp.225-235
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• 2023

Background: This study aimed to analyze the effects of periodontal treatment and individual- and tooth-related factors on tooth extraction in people with disabilities. Methods: The Korea National Health Insurance claims data of individuals with disabilities aged 40~64 years with chronic periodontitis in 2008 were obtained. Of these, data on the disabled who underwent scaling/root plaining, subgingival curettage/periodontal surgery, or non-periodontal treatments, and data on their teeth were selected. The extraction of 716,688 teeth from 39,097 patients was tracked until 2018, and the patient- and tooth-level factors related to tooth loss were identified using a mixed-effect logistic regression analysis. Results: Data from approximately 17% of the teeth were extracted during a follow-up period of approximately 11 years. Among the tooth-level variables, scaling/root planing treatment at baseline and periodontal treatment during the follow-up period were associated with a lower risk of tooth loss (odds ratio=0.692 and 0.769, respectively, p<0.001). Non-vital teeth increased the risk of tooth loss by 3.159 times (p<0.001). Among the patient-level variables, females were less likely to have lost their teeth than males, and those with orthopedic impairment or brain lesions/mental disabilities, a higher age group, lower income level, or residents in medium/small cities or rural areas were more likely to have lost their teeth (p<0.001). Conclusion: Through approximately 11 years of follow-up, scaling or root planing, experience with periodontal treatment at least once, female sex, older age, lower income, smaller residential areas, type of disability, and pulp vitality were found to be associated with tooth loss in individuals with disabilities aged 40~64 years with chronic periodontitis. To prevent tooth loss in individuals with disabilities, it is necessary to establish a dental treatment plan that considers the timing of periodontal treatment and the characteristics of the patient and teeth.

• Journal of the Korean Society of Radiology
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• v.81 no.1
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• pp.243-247
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• 2020

We report a rare case of hyperglycemia-related osmotic demyelination syndrome (ODS) with focus on the imaging findings. A 61-year-old man with diabetes was admitted for general weakness and severe thirst. A few days later, he complained of dysarthria, dysphasia, and dysmetria. Laboratory examinations showed significant hyperglycemia, but normal electrolyte levels. Brain MRI revealed T2-signal abnormalities that were symmetrical, non-space occupying, and located in the central pons with a peripheral sparing pattern, which were suggestive of ODS. In addition, subsequent MRI revealed progression of signal hyperintensity; however, the patient's symptoms improved.

• Korean Journal of Radiology
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• v.24 no.5
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• pp.444-453
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• 2023

Objective: Meningeal lymphatic vessels are predominantly located in the parasagittal dural space (PSD); these vessels drain interstitial fluids out of the brain and contribute to the glymphatic system. We aimed to investigate the ability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the dynamic changes in the meningeal lymphatic vessels in PSD. Materials and Methods: Eighteen participants (26-71 years; male:female, 10:8), without neurological or psychiatric diseases, were prospectively enrolled and underwent DCE-MRI. Three regions of interests (ROIs) were placed on the PSD, superior sagittal sinus (SSS), and cortical vein. Early and delayed enhancement patterns and six kinetic curve-derived parameters were obtained and compared between the three ROIs. Moreover, the participants were grouped into the young (< 65 years; n = 9) or older (≥ 65 years; n = 9) groups. Enhancement patterns and kinetic curve-derived parameters in the PSD were compared between the two groups. Results: The PSD showed different enhancement patterns than the SSS and cortical veins (P < 0.001 and P < 0.001, respectively) in the early and delayed phases. The PSD showed slow early enhancement and a delayed wash-out pattern. The six kinetic curve-derived parameters of PSD was significantly different than that of the SSS and cortical vein. The PSD washout rate of older participants was significantly lower (median, 0.09; interquartile range [IQR], 0.01-0.15) than that of younger participants (median, 0.32; IQR, 0.07-0.45) (P = 0.040). Conclusion: This study shows that the dynamic changes of meningeal lymphatic vessels in PSD can be assessed with DCE-MRI, and the results are different from those of the venous structures. Our finding that delayed wash-out was more pronounced in the PSD of older participants suggests that aging may disturb the meningeal lymphatic drainage.

• Journal of the Korean Society of Radiology
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• v.18 no.3
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• pp.231-237
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• 2024

Brain injury causes persistent disability in survivors, and epidural hematoma(EDH) and subdural hematoma (SDH) resulting from cerebral hemorrhage can be considered one of the major clinical diseases. In this study, we attempted to automatically segment and hematomas due to cerebral hemorrhage in three dimensions based on computed tomography(CT) images. An improved GVF(gradient vector flow) algorithm was implemented for automatic segmentation of hematoma. After calculating and repeating the gradient vector from the image, automatic segmentation was performed and a 3D model was created using the segmentation coordinates. As a result of the experiment, accurate segmentation of the boundaries of the hematoma was successful. The results were found to be good even in border areas and thin hematoma areas, and the intensity, direction of spread, and area of the hematoma could be known in various directions through the 3D model. It is believed that the planar information and 3D model of the cerebral hemorrhage area developed in this study can be used as auxiliary diagnostic data for medical staff.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.40-47
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• 2011

Purpose : Norovirus infection, a common cause of community-acquired gastroenteritis, can also lead to severe illness in immunocompromised patients. We investigated clinical manifestations of norovirus infection in pediatric cancer patients. Methods : Stool specimens were collected from pediatric patients with gastrointestinal symptoms between November 2008 and September 2009 at Samsung Medical Center, Seoul, Korea. Norovirus infection was identified by reverse-transcription polymerase chain reaction (RT-PCR). A retrospective chart review was performed in pediatric cancer patients who were diagnosed with norovirus infection. Results : Ten patients were diagnosed with norovirus infection by RT-PCR in stool samples. The median age was 0.83 years (range 0.25-5.5 years) and the male to female ratio was 1.5:1 (6 males and 4 females). Underlying diseases were hematologic malignancies (4/10, 40%), neuroblastoma (4/10, 40%), and brain tumors (2/10, 20%). Three patients were infected before hematopoietic cell transplantation (HCT) and four patients after HCT. All patients had diarrhea (10/10, 100%), with a median frequency of diarrhea of 8.5 times/day (range 4-22 times/day). Median virus shedding duration was 72.5 days (range 19-299 days). Four patients with pneumatosis intestinalis were conservatively treated with bowel rest and total parenteral nutrition. One patient with severe diarrhea and bloody stool had concomitant chronic gut graft-versus-host disease (GVHD). Norovirus infection-related mortality was not observed. Conclusion : Norovirus infection can cause significant clinical manifestations with prolonged viral shedding in immunocompromised patients. Norovirus should be considered in pediatric cancer patients with severe gastrointestinal symptoms.