• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.469-478
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• 2022

WNT signaling plays an important role in cardiac development, but abnormal activity is often associated with cardiac hypertrophy, myocardial infarction, remodeling, and heart failure. The effect of WNT signaling on regulation of atrial natriuretic peptide (ANP) secretion is unclear. Therefore, the purpose of this study was to investigate the effect of Wnt agonist 1 (Wnta1) on ANP secretion and mechanical dynamics in beating rat atria. Wnta1 treatment significantly increased atrial ANP secretion and pulse pressure; these effects were blocked by U73122, an antagonist of phospholipase C. U73122 also abolished the effects of Wnta1-mediated upregulation of protein kinase C (PKC) β and γ expression, and the PKC antagonist Go 6983 eliminated Wnta1-induced secretion of ANP. In addition, Wnta1 upregulated levels of phospho-transforming growth factor-β activated kinase 1 (p-TAK1), TAK1 banding 1 (TAB1) and phospho-activating transcription factor 2 (p-ATF2); these effects were blocked by both U73122 and Go 6983. Wnta1-induced ATF2 was abrogated by inhibition of TAK1. Furthermore, Wnta1 upregulated the expression of T cell factor (TCF) 3, TCF4, and lymphoid enhancer factor 1 (LEF1), and these effects were blocked by U73122 and Go 6983. Tak1 inhibition abolished the Wnta1-induced expression of TCF3, TCF4, and LEF1 and Wnta1-mediated ANP secretion and changes in mechanical dynamics. These results suggest that Wnta1 increased the secretion of ANP and mechanical dynamics in beating rat atria by activation of PKC-TAK1-ATF2-TCF3/LEF1 and TCF4/LEF1 signaling mainly via the WNT/Ca²⁺ pathway. It is also suggested that WNT-ANP signaling is implicated in cardiac physiology and pathophysiology.

• Physical Therapy Korea
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• v.31 no.2
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• pp.167-173
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• 2024

Background: Stress urinary incontinence (SUI) impacts the social, physical, and psychological well-being and quality of life of the patient. Several techniques exist for its management, including transcutaneous electrical stimulation (TES). Objects: We aimed to demonstrate the effects of TES on ultrasonographic variables and quality of life in women with SUI. Methods: This prospective study recruited 21 women who had been diagnosed with grade 1 or 2 SUI between July 2018 and March 2019. The exclusion criteria were pregnancy and a history of urogenital surgery. All participants were assessed at baseline and 8 weeks after intervention initiation. The bladder neck position (BNP), length of the urethra (LU), funneling index (FI), and rhabdosphincter thickness (RT) were measured. The Incontinence-Quality of Life (I-QOL) was used to assess incontinence-specific quality of life. Statistical significance level was set at p < 0.05. Results: Twenty-one patients with SUI used TES for 8 weeks. BNP and FI significantly decreased after intervention (p < 0.05). LU, anterior and posterior RT (indicators of external sphincter hypertrophy) significantly increased post-intervention (p < 0.05). The total I-QOL score increased from 64.81 to 71.86 after the intervention (p < 0.05). Conclusion: This intervention improved BNP, LU, FI, RT, and subjective indicators such as quality of life in women with SUI. Therefore, TES can be an effective non-surgical treatment method for improving SUI symptoms and quality of life in these patients.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.1
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• pp.111-119
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• 2020

In vascular smooth muscle, K⁺ channels, such as voltage-gated K⁺ channels (Kv), inward-rectifier K⁺ channels (Kir), and big-conductance Ca²⁺-activated K⁺ channels (BK_Ca), establish a hyperpolarized membrane potential and counterbalance the depolarizing vasoactive stimuli. Additionally, Kir mediates endothelium-dependent hyperpolarization and the active hyperemia response in various vessels, including the coronary artery. Pulmonary arterial hypertension (PAH) induces right ventricular hypertrophy (RVH), thereby elevating the risk of ischemia and right heart failure. Here, using the whole-cell patch-clamp technique, we compared Kv and Kir current densities (I_Kv and I_Kir) in the left (LCSMCs), right (RCSMCs), and septal branches of coronary smooth muscle cells (SCSMCs) from control and monocrotaline (MCT)-induced PAH rats exhibiting RVH. In control rats, (1) I_Kv was larger in RCSMCs than that in SCSMCs and LCSMCs, (2) I_Kv inactivation occurred at more negative voltages in SCSMCs than those in RCSMCs and LCSMCs, (3) I_Kir was smaller in SCSMCs than that in RCSMCs and LCSMCs, and (4) I_BKCa did not differ between branches. Moreover, in PAH rats, I_Kir and I_Kv decreased in SCSMCs, but not in RCSMCs or LCSMCs, and I_BKCa did not change in any of the branches. These results demonstrated that SCSMC-specific decreases in I_Kv and I_Kir occur in an MCT-induced PAH model, thereby offering insights into the potential pathophysiological implications of coronary blood flow regulation in right heart disease. Furthermore, the relatively smaller I_Kir in SCSMCs suggested a less effective vasodilatory response in the septal region to the moderate increase in extracellular K⁺ concentration under increased activity of the myocardium.

• Journal of the Korean Society of School Health
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• v.1 no.1
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• pp.114-132
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• 1988

Aiming to appraise student's health status and recommend improvement and strengthening of the school health services, statistical analysis of the results of health examination were done with summarized data which were collected nation-wide through the Ministry of Education. After analysis of data obtained, the results of the study summarized as follows; 1) Requested Adequate care Requested Adequate care showed from 5 % to 3% in 1962 and 1984 respectively. In sexes, Requested Adequate in girls (2.8%) more apparent than in boys (2.5%) 2) Eyes i) Weak vision, abnormal refraction of eyes (myopia, hypermetropia and astigmatism), eye diseases (trachoma, others) were found as shown in the Table 2, Figure 3. Weak vision and abnormal refraction of eyes showed from 2 % (Elementary), 5 % ( Secondary) to 4 % (Elementary), 14 % (Secondary) in 1962 and 1984 respectively. In both sexes, the older the age of students the more weak vision and abnormal refraction of eyes had rapidly increased especially in over 15-year old. ii) Eye diseases (trachoma, others) showed from 2% to age of students the more diseases had students. 3) Ear, nose and pharynx Hearing disturbance, ear diseases (otitis mediae, others), nose (empyema, hypertrophy) and pharynx diseases were found as following 1) Hearing disturbance was found from 0.3%(Elementary), 1 %(Secondary) to 0.05 % (Elementary), 0.4 % (Secondary) in 1962 and 1984 respectively, however, recently the older the age of students the more had students. ii) Ear diseases showed from 1.7 % (Elementary) 1.0 % (Secondary) to 0.3 %(Elementary), 0.5%(Secondary) in 1962 and 1984 respectively. iii) In diseases of the nose and pharynx, tonsilitis showed from 2.5% (Elementary), 3.5 % (Secondary) to 1.8 % ( Elementary). 2.5% (Secondary) in 1962 and 1984 respectively. 4) Skin Infectious skin diseases and other skin diseases were found from 1.5% to 0.6% in 1962 am 1984 respectively. 5) Teeth Dental caries (in milk and permanent teeth) and otner oral diseases are shown from 12 % (Elementary), 8%(Secondary) to 75%( Elementary), 25% (Secondary) in 1962 and 1984 respectively. 6) Other defects and diseases A relatively higher morbidity was shown in the tubercular diseases, in anemia, and in heart diseases among the tuberculous diseases, nodular diseases, Pleurisy, heart diseases, anemia, beriberi, hernia, neurasthenia, speech difficulty, mental disorders, bone dysformity, motion difficulty of extremities. In both sexes, tuberculous diseases were found almost equally in both sexes and anemia in girls was more apparent than in boys. Trying to provide more effective health services in schools : i) A better and more effective physical examination should be carried out in each school and prior to the physical examination, the qualified daily observation of children by teacher should be keenly practiced. ii) According to the results of the required annual physical examination the leading cause of morbidity were dental caries, myopia, angina and otitis mediae and fore these diseases follow up should be carried out. iii) For prevention and treatment of diseases and defects health education for students in the classroom as well as to parents is urgently requested.

• Journal of Chest Surgery
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• v.43 no.6
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• pp.627-634
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• 2010

Background: The durability of the tissue valve is important in choice between a mechanical valve and a tissue valve in cardiac surgery. We studied the mid-term results of tissue valve in the aortic position. Material and Method: The subjects were 380 patients who had undergone aortic prosthesis replacement between May 1990 and March 2009. We retrospectively analyzed hospital and outpatient records: the mean age was $69{\pm}9$ years; the male to female ratio was 227 : 162; and the mean follow-up duration was $46.7{\pm}40.8$ months (range 0~196 months). Result: 389 surgical cases in total had been taken with 380 patients. Early death occurred in 15 patients (3.9%). Overall survival rate at 1, 5 and 10 years were 92.3%, 78.1% and 54.2% respectively. Freedom from reoperation at 1, 5 and 10 years were 98.4%, 97.1% and 91.7% respectively. Freedom from structural valvular deterioration at 1, 5 and 10 years were 96.1%, 92.3% and 88.0% respectively. In the multivariate analysis of preoperative risk factors, young age (p<0.001) was significant risk factor for reoperation. High peak velocity in the postoperative period (p=0.034) and young age (p=0.029) were significant risk factors for structural valvular deterioration. Old age (p=0.001), long bypass time (p=0.035), concomitant coronary artery bypass graft surgery (p=0.003) and preoperative low left ventricular ejection fraction (p=0.003) were significant factors for early mortality. Preoperative estimated glomerular filtration rate (< 60 mL/min) (p=0.025) and persistent left ventricular hypertrophy (p=0.032) were the risk factors for late mortality. Conclusion: This study showed that the freedom from reoperation and the freedom from structural valvular deterioration in aortic tissue valve replacement were acceptable. It will be necessary to conduct further studies with long-term follow-up and more patients.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.9-14
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• 2016

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the $Na^+-K^+$-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain ($3.0{\mu}mol/L$) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 ($3.0{\mu}mol/L$), an inhibitor for reverse mode of $Na^+-Ca^{2+}$ exchangers (NCX), but did not by L-type $Ca^{2+}$ channel blocker nifedipine ($1.0{\mu}mol/L$) or protein kinase A (PKA) selective inhibitor H-89 ($3.0{\mu}mol/L$). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline ($100.0{\mu}mol/L$), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP ($0.5{\mu}mol/L$) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 ($30{\mu}mol/L$), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

• Journal of Chest Surgery
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• v.39 no.10 s.267
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• pp.775-778
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• 2006

Hypertrophic cardiomyopathy is characterized by inappropriate hypertrophy of the myocardium and is associated with various clinical presentations ranging from complete absence of symptoms to sudden, unexpected death. These are caused by dynamic obstruction of the left ventricular outflow tract and surgical approaches were initiated. But, the complete resection of hypertrophied midventricular septum is impossible by standard, transaortic approach, because of narrow vision and limited approach. And it leads to inadequate excision, will leave residual left ventricular out-flow tract obstruction or systolic anterior motion of mitral leaflet, and limit symptomatic improvement and patient's survival. We report a case of extended septal myectomy for hypertrophic cardiomyopathy of mid-septum in a child. The extended septal myectomy was performed by aortotomy and left ventricular apical incision, and made possible the complete resection of mid-ventricular septum, abnormal papillary muscles and chordae. The patient's symptom was improved and the postoperative course was uneventful.

• Journal of fish pathology
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• v.8 no.1
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• pp.57-67
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• 1995

Twenty-four hours, acute toxicity and the histopathological effect of formaline to flounder, Paralichthys olivaceus larvae were examined. The $LC_{50}$ values obtained to farmaline were 2,520 ppm in 1 hour treatment. 1.610 ppm in 2 hours treatment, 868 ppm in 4 hours treatment and 141 ppm in 24 hours treatment. Many pathological features such as hypertrophy of mucous and epithelial cells in secondary gill lamella, hyaline droplet degeneration of tubular epithelial cells in the proximal convoluted segment of renal tubules, focal or massive necrosis in liver cells and pycnotic nucleus in heart cells were recognized. The above results were discussed in relation to the application of formaline as therapeutic agent in flounder disease.

• Toxicological Research
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• v.35 no.1
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• pp.45-63
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• 2019

In view of the growing industrial use of Bacterial cellulose (BC), and taking into account that it might become airborne and be inhaled after industrial processing, assessing its potential pulmonary toxic effects assumes high relevance. In this work, the murine model was used to assess the effects of exposure to respirable BC nanofibrils (nBC), obtained by disintegration of BC produced by Komagataeibacter hansenii. Murine bone marrow-derived macrophages ($BMM{\Phi}$) were treated with different doses of nBC (0.02 and 0.2 mg/mL, respectively 1 and $10{\mu}g$ of fibrils) in absence or presence of 0.2% Carboxymethyl Cellulose (nBCMC). Furthermore, mice were instilled intratracheally with nBC or nBCMC at different concentrations and at different time-points and analyzed up to 6 months after treatments. Microcrystaline $Avicel-plus^{(R)}$ CM 2159, a plant-derived cellulose, was used for comparison. Markers of cellular damage (lactate dehydrogenase release and total protein) and oxidative stress (hydrogen peroxidase, reduced glutathione, lipid peroxidation and glutathione peroxidase activity) as well presence of inflammatory cells were evaluated in brochoalveolar lavage (BAL) fluids. Histological analysis of lungs, heart and liver tissues was also performed. BAL analysis showed that exposure to nBCMC or CMC did not induce major alterations in the assessed markers of cell damage, oxidative stress or inflammatory cell numbers in BAL fluid over time, even following cumulative treatments. $Avicel-plus^{(R)}$ CM 2159 significantly increased LDH release, detected 3 months after 4 weekly administrations. However, histological results revealed a chronic inflammatory response and tissue alterations, being hypertrophy of pulmonary arteries (observed 3 months after nBCMC treatment) of particular concern. These histological alterations remained after 6 months in animals treated with nBC, possibly due to foreign body reaction and the organism's inability to remove the fibers. Overall, despite being a safe and biocompatible biomaterial, BC-derived nanofibrils inhalation may lead to lung pathology and pose significant health risks.