• Natural Product Sciences
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• 제18권3호
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• pp.183-189
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• 2012

It is well known that inflammation is associated with neurodegenerative disorders, including Alzheimer' disease, Parkinson's disease and ischemia. Nitric oxide (NO), a pro-inflammatory mediator, is produced by inducible NO synthase (iNOS) in microglia as well as macrophages and appears to account for neurodegeneration. In this study, we aimed to isolate NO inhibitors from Pyrus pyrifolia by activity guided purification. As a result, we identified daucosterol and ${\beta}$-sitosterol, which have not been isolated from this plant before. This article also describes NO inhibitory activities of the methanol extract of Pyrus pyrifolia fruit and the isolated compounds from this, which are lupeol, betulin, betulinic acid, ${\beta}$-sitosterol and daucosterol, in LPS-activated RAW 264.7 and BV2 cell lines. Western blot analysis was performed to clarify the underlying mechanism of NO inhibition in the two cell lines.

• BMB Reports
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• 제55권9호
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• pp.453-458
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• 2022

Diabetes mellitus (DM) is a serious disease in which blood sugar levels rise abnormally because of failed insulin production or decreased insulin sensitivity. Although many studies are being conducted for the treatment or early diagnosis of DM, it is not fully understood how mitochondrial genome (mtDNA) abnormalities appear in patients with DM. Here, we induced iPSCs from fibroblasts, PBMCs, or pancreatic cells of three patients with type 2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without any tendency among tissues or patients. In T2D patients, 62% (21/34) of iPSC clones harbored multiple mtDNA mutations, of which 37% were homoplasmy at the 100% mutation level compared to only 8% in non-diabetes. We next selected iPSC clones that were a wild type or carried mutations and differentiated into pancreatic cells. Oxygen consumption rates were significantly lower in cells carrying mutant mtDNA. Additionally, the mutant cells exhibited decreased production of insulin and reduced secretion of insulin in response to glucose. Overall, the results suggest that screening mtDNA mutations in iPSCs from patients with T2D is an essential step before pancreatic cell differentiation for disease modeling or autologous cell therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10217-10223
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• 2015

Hyperactivated ${\alpha}2$-6-sialylation on N-glycans due to overexpression of the Golgi enzyme ${\beta}$-galactoside: ${\alpha}2$-6-sialyltransferase (ST6Gal-I) often correlates with cancer progression, metastasis, and poor prognosis. This study was aimed to determine the association between ST6Gal-I expression and the risk of recurrence and survival of patients with localized clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 391 patients (265 in training cohort and 126 in validation cohort) with localized ccRCC underwent nephrectomy at a single center. Tissue microarrays were constructed for immunostaining of ST6Gal-I. Prognostic value and clinical outcomes were evaluated. High ST6Gal-I expression was associated with Fuhrman grade (p<0.001 and p=0.016, respectively) and the University of California Los-Angeles Integrated Staging System (UISS) score (p=0.004 and p=0.017, respectively) in both cohorts. Patients with high ST6Gal-I expression had significantly worse overall survival (OS) (p<0.001 and p<0.001, respectively) and recurrence free survival (RFS) (p<0.001 and p=0.002, respectively) than those with low expression in both cohorts. On multivariate analysis, ST6Gal-I expression remained associated with OS and RFS even after adjusting for the UISS score. Stratified analysis suggested that the association is more pronounced among patients with low and intermediate-risk disease defined by the UISS score. High ST6Gal-I expression is a potential independent adverse predictor of survival and recurrence in ccRCC patients, and the prognostic value is most prominent in those with low and intermediate-risk disease defined by the UISS score.

• International Journal of Stem Cells
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• 제15권1호
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• pp.85-94
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• 2022

Background and Objectives: Brain organoids have the potential to improve our understanding of brain development and neurological disease. Despite the importance of brain organoids, the effect of vascularization on brain organoids is largely unknown. The objective of this study is to develop vascularized organoids by assembling vascular spheroids with cerebral organoids. Methods and Results: In this study, vascularized spheroids were generated from non-adherent microwell culture system of human umbilical vein endothelial cells, human dermal fibroblasts and human umbilical cord blood derived mesenchymal stem cells. These vascular spheroids were used for fusion with iPSCs induced cerebral organoids. Immunostaining studies of vascularized organoids demonstrated well organized vascular structures and reduced apoptosis. We showed that the vascularization in cerebral organoids up-regulated the Wnt/β-catenin signaling. Conclusions: We developed vascularized cerebral organoids through assembly of brain organoids with vascular spheroids. This method could not only provide a model to study human cortical development but also represent an opportunity to explore neurological disease.

• 동의생리병리학회지
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• 제17권5호
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• pp.1251-1256
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• 2003

To determine the effect of Zibachunggan-tang(ZCT) on the process of lipopolysaccharide (LPS)-induced nuclear factor-kBp65 (NF-kBp65) activation, and LPS-induced expression of pro-inflammatory proteins including tumor necrosis factor-α (TNF-α), nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in HepG2 cell. Immunoblot analysis showed that the level of nucleic NF-kBp65 was rapidly up-regulated and cytosolic inhibitory I-kBα was down-regulated by LPS challenge. While ZCT inhibited an increase of NF-kBp65 and degradation of I-kBα in HepG2 cell. Beside LPS-induced expression of a group of genes, such as TNF-α, inducible iNOS and COX-2, are repressed by ZCT. It may be concluded that ZCT attenuates the progress of LPS-induced inflammation by reduction of NF-kBp65 activation. The ZCT would be useful as a therapeutic agent for endotoxin-induced liver disease.

• Journal of Chest Surgery
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• 제50권2호
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• pp.86-93
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• 2017

Background: The influence of lifestyle diseases on postoperative complications and long-term survival in patients with non-small cell lung cancer (NSCLC) is unclear. The aim of this study was to determine whether lifestyle diseases were significant risk factors of perioperative and long-term surgical outcomes in elderly patients with stage I NSCLC. Methods: Between December 1995 and November 2013, 110 patients aged 65 years or older who underwent surgical resection of stage I NSCLC at Dong-A University Hospital were retrospectively studied. We assessed the presence of the following lifestyle diseases as risk factors for postoperative complications and long-term mortality: diabetes, hypertension, chronic obstructive pulmonary disease, stroke, and ischemic heart disease. Results: The mean age of the patients was 71 years (range, 65 to 82 years). Forty-six patients (41.8%) had hypertension, making it the most common lifestyle disease, followed by diabetes (n=23, 20.9%). The in-hospital mortality rate was 0.9% (n=1). The 3-year and 5-year survival rates were 78% and 64%, respectively. Postoperative complications developed in 32 patients (29.1%), including 7 (6.4%) with prolonged air leakage, 6 (5.5%) with atrial fibrillation, 5 (4.5%) with delirium and atelectasis, and 3 (2.7%) with acute kidney injury and pneumonia. Univariate and multivariate analyses showed that the presence of a lifestyle disease was the only independent risk factor for postoperative complications. In survival analysis, univariate analysis showed that age, smoking, body mass index, extent of resection, and pathologic stage were associated with impaired survival. Multivariate analysis revealed that resection type (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.08 to 4.49; p=0.030) and pathologic stage (HR, 1.89; 95% CI, 1.02 to 3.49; p=0.043) had independent adverse impacts on survival. Conclusion: This study demonstrated that the presence of a lifestyle disease was a significant prognostic factor for postoperative complications, but not of survival, in elderly patients with stage I NSCLC. Therefore, postoperative complications may be influenced by the presence of a lifestyle disease.

• 대한수의학회지
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• 제57권1호
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• pp.31-36
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• 2017

Japanese encephalitis (JE) is an important zoonosis caused by the mosquito-transmitted JE virus (JEV), which is a causative agent of reproductive failure in pregnant sows. Detection of JEV antibodies in swine is performed by hemagglutination inhibition (HI), virus neutralization (VN), and the plaque reduction neutralization test (PRNT). The most stringent PRNT is the 90% endpoint PRNT ($PRNT_{90}$). These conventional assays are difficult to carry out in diagnostic laboratories with insufficient instruments or cell culture systems. An alternative assay that is easily conducted and time efficient is required. In this study, we improved the indirect enzyme-linked immunosorbent assay (I-ELISA) with clarified antigen for the detection of JEV antibodies. The I-ELISA results obtained from 175 swine serum samples were compared with HI, VN, and $PRNT_{90}$ results. The sensitivity of I-ELISA was 91.8%, 95.0%, and 94.7% compared with HI, VN, and $PRNT_{90}$ results, respectively. The specificity of I-ELISA was 92.2%, 94.7%, and 94.7% compared with HI, VN, and $PRNT_{90}$ results, respectively. Moreover, the I-ELISA results were significantly correlated with the HI (r = 0.93), VN (r = 0.95), and $PRNT_{90}$ (r = 0.92) results. These results suggest that the improved I-ELISA is useful for serosurveillance of JEV in swine.

• Reproductive and Developmental Biology
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• 제35권4호
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• pp.427-434
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• 2011

Mitochondria diseases have been reported to involve structural and functional defects of complex I-V. Especially, many of these diseases are known to be related to dysfunction of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I). The dysfunction of mitochondria complex I is associated with neurodegenerative disorders, such as Parkinson's disease, Huntington's disease, and Leber's hereditary optic neuropathy (LHON). Mammalian mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) is largest and consists of at least 46 different subunits. In contrast, the NDI1 gene of Saccharomyces cerevisiae is a single subunit rotenone-insensitive NADH-quinone oxidoreductase that is located on the matrix side of the inner mitochondrial membrane. The Saccharomyces cerevisiae NDI1 gene using a recombinant adeno-associated virus vector (rAAV-NDI1) was successfully expressed in AML12 mouse liver hepatocytes and the NDI1-transduced cells were able to grow in media containing rotenone. In contrast, control cells that did not receive the NDI1 gene failed to survive. The expressed Ndi1 enzyme was recognized to be localized in mitochondria by confocal immunofluorescence microscopic analyses and immunoblotting. Using digitonin-permeabilized cells, it was shown that the NADH oxidase activity of the NDI1-transduced cells was not affected by rotenone which is inhibitor of complex I, but was inhibited by antimycin A. Furthermore, these results indicate that Ndi1 can be functionally expressed in the AML12 mouse liver hepatocytes. It is conceivable that the NDI1 gene is powerful tool for gene therapy of mitochondrial diseases caused by complex I deficiency. In the future, we will attempt to functionally express the NDI1 gene in mouse embryonic stem (mES) cell.

• 통합자연과학논문집
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• 제6권3호
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• pp.143-150
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• 2013

Prevailing role of intracellular amyloid ${\beta}$ ($iA{\beta}$) in Alzheimer's disease (AD) initiation and progression attracts more and more attention in recent years. To address whether $iA{\beta}$ induces early alterations of electrophysiological properties in cultured human primary neurons, we delivered $iA{\beta}$ with adenovirus and measured the electrophysiological properties of infected neurons with whole-cell recordings. Our results show that $iA{\beta}$ induces an increase in neuronal resting membrane potentials, a decrease in $K^+$ currents and a hyperpolarizing shift in voltage-dependent activation of $K^+$ currents. These results suggest the electrophysiological impairments induced by $iA{\beta}$ may be responsible for its neuronal toxicity.

• Journal of Chest Surgery
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• 제25권5호
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• pp.504-510
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• 1992

Overall 25,095 cases of general thoracic surgery were analysed, which were performed by 48 institutes in Korea during recent 6 years[242 hospital-years]. The proportions of tumorous disease and infectious disease to be operated were 6,864 cases[27.4%] and 6,775 cases [27.0%], The most common organ involved for operation was lung-bronchus 16,542 cases [69.5%], and remainders were pleura 2,500 [10.0%], esophagus 2,433[9.7%], mediastinum 1,902[7.6%], chest wall 1,297 [5.2%], and diaphragm 421 [1.7%] in order. Among 6,864 cases of tumorous diseases, the most common causes for operation were lung-bronchus tumor 3132 cases [45.6%] and most of them were lung cancer 2,731 cases [88.7%]. In the 2,019 cases of primary lung cancer with known cell type, squamous cell carcinoma 1,296 cases [64.2%] and adenocarcinoma 460 cases [22.8%] were the most. The common types in the 1,207 cases of mediastinal tumor with known cell type were neurogenic tumor 348 cases [28.8%], thymoma 311 [25.8%], and teratoma 252[20.9%]. The annual cases of operation for tumorous disease including malignant tumor were increased steadily. Operation for infectious lung diseases [including bronchiectasis and tuberculosis] were about twice common than infectious pleural disease [i.e. empyema], and operations for tuberculous disease occupied about half cases of infectious lung disease. In 11,456 cases of other disease entities, excluding tumorous and infectious disease, there were bullous lung disease 9,074 cases[79.2%], benign esophageal disease 484[4.2%], myasthenia gravis 356[3.1%], chest wall deformity 483[4.2%], and diaphragmatic lesion 421[3. 7%] in order. We propose that above results for inquiry can be used as the basic data of general thoracic surgery in Korea.