• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.11.1-11.9
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• 2018

Estrogen has diverse effects on cardiovascular function, including regulation of the contractile response to vasoactive substances such as serotonin. The serotonin system recently emerged as an important player in the regulation of vascular tone in humans. However, hyperreactivity to serotonin appears to be a critical factor for the pathophysiology of hypertension. In this study, we examined the modulatory mechanisms of estrogen in serotonin-induced vasoconstriction by using a combinatory approach of isometric tension measurements, molecular biology, and patch-clamp techniques. $17{\beta}$-Estradiol (E2) elicited a significant and concentration-dependent relaxation of serotonin-induced contraction in deendothelialized aortic strips isolated from male rats. E2 triggered a relaxation of serotonin-induced contraction even in the presence of tamoxifen, an estrogen receptor antagonist, suggesting that E2-induced changes are not mediated by estrogen receptor. Patch-clamp studies in rat arterial myocytes showed that E2 prevented Kv channel inhibition induced by serotonin. Serotonin increased Src activation in arterial smooth muscle required for contraction, which was significantly inhibited by E2. The estrogen receptor-independent inhibition of Src by E2 was confirmed in HEK293T cells that do not express estrogen receptor. Taken together, these results suggest that estrogen exerts vasodilatory effects on serotonin-precontracted arteries via Src, implying a critical role for estrogen in the prevention of vascular hyperreactivity to serotonin.

• Integrative Medicine Research
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• v.3 no.4
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• pp.204-210
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• 2014

The aim of this review was to understand the effects of ${\beta}$-adrenergic stimulation on oxidative stress, structural remodeling, and functional alterations in the heart and cerebral artery. Diverse stimuli activate the sympathetic nervous system, leading to increased levels of catecholamines. Long-term overstimulation of the ${\beta}$-adrenergic receptor (${\beta}AR$) in response to catecholamines causes cardiovascular diseases, including cardiac hypertrophy, stroke, coronary artery disease, and heartfailure. Although catecholamines have identical sites of action in the heart and cerebral artery, the structural and functional modifications differentially activate intracellular signaling cascades. ${\beta}AR$-stimulation can increase oxidative stress in the heart and cerebral artery, but has also been shown to induce different cytoskeletal and functional modifications by modulating various components of the ${\beta}AR$ signal transduction pathways. Stimulation of ${\beta}AR$ leads to cardiac dysfunction due to an overload of intracellular $Ca^{2+}$ in cardiomyocytes. However, this stimulation induces vascular dysfunction through disruption of actin cytoskeleton in vascular smooth muscle cells. Many studies have shown that excessive concentrations of catecholamines during stressful conditions can produce coronary spasms or arrhythmias by inducing $Ca^{2+}$-handling abnormalities and impairing energy production in mitochondria, In this article, we highlight the different fates caused by excessive oxidative stress and disruptions in the cytoskeletal proteome network in the heart and the cerebral artery in responsed to prolonged ${\beta}AR$-stimulation.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.3
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• pp.183-193
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• 2022

MicroRNAs (miRNAs) regulate gene expression and are biomarkers for coronary atherosclerosis (AS). A novel miRNA-mRNA regulation network of coronary AS still needs to be disclosed. The aim of this study was to analyze potential mRNAs in coronary AS patients and the role of their upstream miR-491-5p in vascular smooth muscle cells (VSMCs). We first confirmed top ten mRNAs according to the analysis from Gene Expression Omnibus database (GSE132651) and examined the expression levels of them in the plaques and serum from AS patients. Five mRNAs (UBE2G2, SLC16A3, POLR2C, PNO1, and AMDHD2) presented significantly abnormal expression in both plaques and serum from AS patients, compared with that in the control groups. Subsequently, they were predicted to be targeted by 11 miRNAs by bioinformatics analysis. Among all the potential upstream miRNAs, only miR-491-5p was abnormally expressed in the plaques and serum from AS patients. Notably, miR-491-5p overexpression inhibited viability and migration, and significantly increased the expression of contractile markers (α-SMA, calponin, SM22α, and smoothelin) in VSMCs. While silencing miR-491-5p promoted viability and migration, and significantly suppressed the expression of α-SMA, calponin, SM22α, and smoothelin. Overall, miR-491-5p targeted UBE2G2, SLC16A3, and PNO1 and regulated the dysfunctions in VSMCs.

• Journal of Korean Neurosurgical Society
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• v.66 no.1
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• pp.53-62
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• 2023

Objective : Deep learning is a machine learning approach based on artificial neural network training, and object detection algorithm using deep learning is used as the most powerful tool in image analysis. We analyzed and evaluated the diagnostic performance of a deep learning algorithm to identify skull fractures in plain radiographic images and investigated its clinical applicability. Methods : A total of 2026 plain radiographic images of the skull (fracture, 991; normal, 1035) were obtained from 741 patients. The RetinaNet architecture was used as a deep learning model. Precision, recall, and average precision were measured to evaluate the deep learning algorithm's diagnostic performance. Results : In ResNet-152, the average precision for intersection over union (IOU) 0.1, 0.3, and 0.5, were 0.7240, 0.6698, and 0.3687, respectively. When the intersection over union (IOU) and confidence threshold were 0.1, the precision was 0.7292, and the recall was 0.7650. When the IOU threshold was 0.1, and the confidence threshold was 0.6, the true and false rates were 82.9% and 17.1%, respectively. There were significant differences in the true/false and false-positive/false-negative ratios between the anterior-posterior, towne, and both lateral views (p=0.032 and p=0.003). Objects detected in false positives had vascular grooves and suture lines. In false negatives, the detection performance of the diastatic fractures, fractures crossing the suture line, and fractures around the vascular grooves and orbit was poor. Conclusion : The object detection algorithm applied with deep learning is expected to be a valuable tool in diagnosing skull fractures.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.5
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• pp.479-491
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• 2024

Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.

• BMB Reports
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• v.54 no.9
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• pp.464-469
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• 2021

Cardiomyocyte differentiation occurs through complex and finely regulated processes including cardiac lineage commitment and maturation from pluripotent stem cells (PSCs). To gain some insight into the genome-wide characteristics of cardiac lineage commitment, we performed transcriptome analysis on both mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs) at specific stages of cardiomyocyte differentiation. Specifically, the gene expression profiles and the protein-protein interaction networks of the mESC-derived platelet-derived growth factor receptor-alpha (PDGFRα)⁺ cardiac lineage-committed cells (CLCs) and hiPSC-derived kinase insert domain receptor (KDR)⁺ and PDGFRα⁺ cardiac progenitor cells (CPCs) at cardiac lineage commitment were compared with those of mesodermal cells and differentiated cardiomyocytes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the genes significantly upregulated at cardiac lineage commitment were associated with responses to organic substances and external stimuli, extracellular and myocardial contractile components, receptor binding, gated channel activity, PI3K-AKT signaling, and cardiac hypertrophy and dilation pathways. Protein-protein interaction network analysis revealed that the expression levels of genes that regulate cardiac maturation, heart contraction, and calcium handling showed a consistent increase during cardiac differentiation; however, the expression levels of genes that regulate cell differentiation and multicellular organism development decreased at the cardiac maturation stage following lineage commitment. Additionally, we identified for the first time the protein-protein interaction network connecting cardiac development, the immune system, and metabolism during cardiac lineage commitment in both mESC-derived PDGFRα⁺ CLCs and hiPSC-derived KDR⁺PDGFRα⁺ CPCs. These findings shed light on the regulation of cardiac lineage commitment and the pathogenesis of cardiometabolic diseases.

• Journal of the Korea Society of Computer and Information
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• v.27 no.5
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• pp.21-28
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• 2022

All health problems that occur in the circulatory system are refer to cardiovascular illness, such as heart and vascular diseases. Deaths from cardiovascular disorders are recorded one third of in total deaths in 2019 worldwide, and the number of deaths continues to rise. Therefore, if it is possible to predict diseases that has high mortality rate with patient's data and AI system, they would enable them to be detected and be treated in advance. In this study, models are produced to predict heart disease, which is one of the cardiovascular diseases, and compare the performance of models with Accuracy, Precision, and Recall, with description of the way of improving the performance of the Decision Tree(Decision Tree, KNN (K-Nearest Neighbor), SVM (Support Vector Machine), and DNN (Deep Neural Network) are used in this study.). Experiments were conducted using scikit-learn, Keras, and TensorFlow libraries using Python as Jupyter Notebook in macOS Big Sur. As a result of comparing the performance of the models, the Decision Tree demonstrates the highest performance, thus, it is recommended to use the Decision Tree in this study.

• Korean Circulation Journal
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• v.52 no.4
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• pp.280-287
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• 2022

Several studies have shown the benefit of complete revascularization (CR) over culprit-only percutaneous coronary intervention (PCI) in patients with ST-segment elevated myocardial infarction (STEMI) and multivessel disease (MVD). Nevertheless, optimal strategy to select targets for non-culprit PCI has not been clarified. In this paper, we critically discuss and compare the safety and efficacy of different strategies for CR in patients with STEMI and MVD using a Bayesian network meta-analysis including all previous randomized controlled trials (RCTs). In Bayesian network meta-analysis of 13 RCTs, culprit-only PCI was associated with higher risk of major adverse cardiac events (MACE), compared with angiography-guided or fractional flow reserve (FFR)-guided CR strategies. However, there was no significant difference between angiography-guided and FFR-guided CR strategies in the risk of MACE and its individual components including all-cause death, cardiac death, myocardial infarction (MI), and revascularization. These evidence support that both angiography-guided and FFR-guided complete revascularization strategies would be reasonable treatment option in patients with STEMI and MVD. If the non-culprit lesion is severe on visual assessment, angiography-guided PCI can be considered. If the non-culprit lesion is intermediate in severity or unclear based on visual assessment, FFR-guided strategy can be used as a reliable and objective tool, providing similar benefits with less stents compared with an angiography-guided strategy. Further RCT is needed to evaluate direct comparison between angiography-guided and FFR-guided CR strategies in patients with STEMI and MVD. Ongoing FRAME-AMI trial (NCT02715518) will provide more evidence regarding this issue.

• Archives of Craniofacial Surgery
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• v.10 no.2
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• pp.97-102
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• 2009

Purpose: To close anterior cranial base, various types of pedicle flaps have been developed previously. However, the results of those pedicle flaps were not constant. To solve such problem, the author designed bipedicle temporalis-pericranial (BTP) flap based on various types of existing flaps and this study intends to introduce this flap and present clinical application case. Methods: The pedicle of the proposed temporalis-pericranial flap is temporalis muscle. The point of this BTP flap is that because of both sides of the unilateral temporalis-pericranial flap are connected by midline pericranial tissue connected with dense vascular network communicate one another locally, that BTP flap can be safely elevated. The case is a 14 months old male patient of frontoethmoidal encephalomeningocele. Surgery was done in a way that after elevating BTP flap and removing encephalomeningocele, BTP flap was moved intracranially, and to prevent cerebrospinal fluid leakage, anterior cranial base was closed. Results: During 1 year and 6 month outpatient tracking observation, no particular finding like CSF leakage, meningitis or hydrocephalus was observed. Conclusion: The benchmarked BTP flap, effective in the treatment of frontoethmoidal encephalomeningocele, is one of the methods to close intracranium and extracranium.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.23 no.5
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• pp.461-470
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• 2001

A unhealthy 58-year-old male patient required extraction of left upper second molar due to advanced periodontitis. Lidocaine contained 1 : 100000 epinephrine for left posterior superior alveolar nerve block was administered in the mucobuccal fold above the second molar to be treated at the local private dental clinic. After four hours of posterior superior alveolar block anesthesia, patient feeled double vision and discomfort of eyeball movement. At next day, he complained difficulty of left eyeball movement, vertigo and diplopia. He was referred to our department via local clinic and department of ophthalomology of our hospital. He was treated by medication and eyeball exercise, and then follow up check. The double vision and medial rectus muscle palsy disappeared patially after 2 months of block anesthesia. We described herein an ocular complication of diplopia and inferior rectus muscle palsy after posterior superior alveolar nerve block for extraction of left upper second molar, and review the cause or origin of this case. The autonomic nervous system is presented as the logical basis for the untoward systems of ophthalmologic sign likely to diplopia and inferior rectus muscle palsy, rather then simple circulation of anesthetic solution in the vascular network.