• Journal of Ginseng Research
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• 제45권6호
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• pp.683-694
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• 2021

Background: Ginsenoside Rg1 (Rg1) has been well documented to be effective against various cardiovascular disease. The aim of this study is to evaluate the effect of Rg1 on mechanical stress-induced cardiac injury and its possible mechanism with a focus on the calcium sensing receptor (CaSR) signaling pathway. Methods: Mechanical stress was implemented on rats through abdominal aortic constriction (AAC) procedure and on cardiomyocytes and cardiac fibroblasts by mechanical stretching with Bioflex Collagen I plates. The effects of Rg1 on cell hypertrophy, fibrosis, cardiac function, [Ca²⁺]_i, and the expression of CaSR and calcineurin (CaN) were assayed both on rat and cellular level. Results: Rg1 alleviated cardiac hypertrophy and fibrosis, and improved cardiac decompensation induced by AAC in rat myocardial tissue and cultured cardiomyocytes and cardiac fibroblasts. Importantly, Rg1 treatment inhibited CaSR expression and increase of [Ca²⁺]_i, which similar to the CaSR inhibitor NPS2143. In addition, Rg1 treatment inhibited CaN and TGF-b1 pathways activation. Mechanistic analysis showed that the CaSR agonist GdCl₃ could not further increase the [Ca²⁺]_i and CaN pathway related protein expression induced by mechanical stretching in cultured cardiomyocytes. CsA, an inhibitor of CaN, inhibited cardiac hypertrophy, cardiac fibrosis, [Ca²⁺]_i and CaN signaling but had no effect on CaSR expression. Conclusion: The activation of CaN pathway and the increase of [Ca²⁺]_i mediated by CaSR are involved in cardiac hypertrophy and fibrosis, that may be the target of cardioprotection of Rg1 against myocardial injury.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.203-210
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• 2015

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms has not been well investigated. In this study, we found that EGCG could significantly reduce natriuretic peptides type A (Nppa), brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy. Taken together, our findings provide the first evidence that the effect of EGCG against cardiac hypertrophy may be attributed to its activation on AMPK-dependent signaling pathway, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.

• Journal of Trauma and Injury
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• 제34권4호
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• pp.242-247
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• 2021

Purpose: Blunt cardiac injuries (BCI) have a wide clinical spectrum, ranging from asymptomatic myocardial contusion to cardiac rupture and death. BCIs rarely require surgical intervention, but can be rapidly fatal, requiring prompt evaluation and surgical treatment in some cases. The aim of this study was to identify potential factors associated with in-hospital mortality after surgery in patients with BCI. Methods: The medical records of 15 patients who had undergone emergency cardiac surgery for BCI between January 2014 and August 2020 were retrospectively reviewed. We included trauma patients older than 18 years admitted to Regional Trauma Center, Gachon University Gil Medical Center during the study period. Clinical and laboratory variables were compared between survivors and non-survivors. Results: Non-survivors showed a significantly higher Injury Severity Score (p=0.001) and Abbreviated Injury Scale in the chest region (p=0.001) than survivors. American Association for the Surgery of Trauma-Organ Injury Scale Grade V injuries were significantly more common in non-survivors than in survivors (p=0.031). Non-survivors had significantly more preoperative packed red blood cell (PRBC) transfusions (p=0.019) and were significantly more likely to experience preoperative cardiac arrest (p=0.001) than survivors. Initial pH (p=0.010), lactate (p=0.026), and base excess (BE; p=0.026) levels showed significant differences between the two groups. Conclusions: Initial pH, lactate, BE, ventricular injury, the amount of preoperative PRBC transfusions, and preoperative cardiac arrest were potential predictors of in-hospital mortality.

• Journal of Chest Surgery
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• 제48권6호
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• pp.422-425
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• 2015

Amyloid deposits in the heart are not exceptional in systemic amyloidosis. The clinical manifestations of cardiac amyloidosis may include restrictive cardiomyopathy, characterized by progressive diastolic and eventually systolic biventricular dysfunction; arrhythmia; and conduction defects. To the best of our knowledge, no previous cases of isolated tricuspid regurgitation as the initial manifestation of cardiac amyloidosis have been reported. We describe a rare case of cardiac amyloidosis that initially presented with severe tricuspid regurgitation in a 42-year-old woman who was successfully treated with tricuspid valve replacement. Unusual surgical findings prompted additional evaluation that established a diagnosis of plasma cell myeloma.

• 제어로봇시스템학회:학술대회논문집
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• 제어로봇시스템학회 2005년도 ICCAS
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• pp.1179-1182
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• 2005

To facilitate the cell based robot research, we presented a micro-mechanical force measurement system for the biological muscle actuators, which utilize glucose as a power source for potential application in a human body or blood vessels. The system is composed of a micro-manipulator, a force transducer with a glass probe, a signal processor, an inverted microscope and video recoding system. Using this measurement system, the contractile force and frequency of the cardiac myocytes were measured in real time and the magnitude of the contractile force of each cardiac myocyte on a different condition was compared. From the quantitative experimental results, we estimated that the force of cardiac myocytes is about $20{\sim}40\;{\mu}$N, and showed that there is difference between the control cells and the micro-patterned cells.

• BMB Reports
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• 제53권2호
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• pp.118-123
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• 2020

Cardiac regeneration with adult stem-cell (ASC) therapy is a promising field to address advanced cardiovascular diseases. In addition, extracellular vesicles (EVs) from ASCs have been implicated in acting as paracrine factors to improve cardiac functions in ASC therapy. In our work, we isolated human cardiac mesenchymal stromal cells (h-CMSCs) by means of three-dimensional organ culture (3D culture) during ex vivo expansion of cardiac tissue, to compare the functional efficacy with human bone-marrow derived mesenchymal stem cells (h-BM-MSCs), one of the actively studied ASCs. We characterized the h-CMSCs as CD90^low, c-kit^negative, CD105^positive phenotype and these cells express NANOG, SOX2, and GATA4. To identify the more effective type of EVs for angiogenesis among the different sources of ASCs, we isolated EVs which were derived from CMSCs with either normoxic or hypoxic condition and BM-MSCs. Our in vitro tube-formation results demonstrated that the angiogenic effects of EVs from hypoxia-treated CMSCs (CMSC-Hpx EVs) were greater than the well-known effects of EVs from BM-MSCs (BM-MSC EVs), and these were even comparable to human vascular endothelial growth factor (hVEGF), a potent angiogenic factor. Therefore, we present here that CD90^lowc-kit^negativeCD105^positive CMSCs under hypoxic conditions secrete functionally superior EVs for in vitro angiogenesis. Our findings will allow more insights on understanding myocardial repair.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.76-76
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• 2003

Pluripotent embryonic stem cells can differentiate into beating cardiomyocytes with proper culture conditions and stimulants via embryo-like aggregates. We describe here the use of mouse embryonic stem (mES03) cells as a reproducible differentiation system for cardiomyocyte. mES03 cells growing in colonies were dissociated and allowed to re-aggregated in suspension [embryoid body (EB) formation〕. To induce cardiomyocytic differentiation, cells were exposed to 0.75% dimethyl sulfoxide (DMSO) during EB formation for 4 days and then another 4 days without DMSO (4+/4-). Thus treated EB was plated onto gelatin-coated dishes for differentiation. Spontaneously contracting colonies which appeared in approximately 4~5 days upon differentiation were mechanically dissected, enzymatically dispersed, plated onto coverslips, and then incubated for another 48~72 hrs. By RT-PCR, robust expression of cardiac myosin heavy chain $\alpha$, cardiac muscle heavy polypeptide 7 $\beta$($\beta$-MHC), cardiac transcription factor GATA4, and skeletal muscle-specific $\alpha$$_1$-subunit of the L-type calcium channel ($\alpha$$_1$CaC $h_{sm}$ ) were detected as early as 8 days after EB formation, but message of cardiac muscle-specific $\alpha$$_1$-subunit of the L-type calcium channel ($\alpha$$_1$CaCh) were reveled at a low level. In contrast, expression of myosin light chain (MLC-2V) and atrial natriuretic factor (ANF) were not detected during EB formation for 8 days. However, a strong expression of the atrial-specific ANF gene was expressed from day 8 onward, which were remained constant in EB. (cardiac specialization and terminal differentiation stage). Electrophysiological examination of spontaneously contracting cells showed ventricle-like action potential 17 days after the EB formation. This study indicates that mES03 cell-derived cardiomyocytes via 4+/4- protocol displayed biochemical and electrophysiological properties of subpopulation of cardiomyocytes.

• Journal of Chest Surgery
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• 제39권11호
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• pp.810-814
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• 2006

배경: 심장에 발생하는 종양은 흔치 않다. 심장종양의 종양에 대한 임상적 특징과 수술 결과를 조사하였다. 대상 및 방법: 1990년 3월부터 2005년 12월까지 35명(남자14명, 여자 21명)의 환자를 대상으로 하였으며 평균 나이는 52.4세였다. 임상 및 병리학적 조사를 후향적으로 시행하였다. 수술은 좌심실 섬유종 1예를 제외한 전 예에서 완전 절제술을 시행하였다. 결과: 양성은 30예였으며 그중 점액종이 29예, 섬유종이 1예였다. 악성은 5예로 골육종, 미분류 점액성 육종, 간세포암, 신세포암, 그리고 난황낭암이 각 1예였다. 양성인 경우 수술 사망은 없었으며 완전절제 후 추적이 가능했던 27예의 경우 재발된 예는 없었다. 악성의 경우 4예가 술 후 6개월 이내에 사망하였다. 결론: 좌심방의 점액종이 가장 많았으며 양성의 경우 외과적 치료는 효과적이었으나 악성인 경우 예후는 매우 불량하였다.

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.67-67
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• 2006

• Reproductive and Developmental Biology
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• 제32권1호
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• pp.21-25
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• 2008

Bone marrow mesenchymal stem cells (BMMSCs) have the capacity for self-renewal and differentiation into a variety of cell types. They represent an attractive source of cells for gene and cell therapy. The purpose of this study is to direct the specific expression of the DsRed reporter gene in $Sca-1^+$ BMMSCs differentiated into a cardiomyogenic lineage. We constructed the prMLC-2v-DsRed vector expressing DsRed under the control of the 309 tp fragment of the rat MLC-2v 5'-flanking region. The specific expression of the DsRed reporter gene under the transcriptional control of the 309 bp fragment of the rat MLC-2v promoter was tested in 5-azacytidine healed-$Sca-1^+$ BMMSCs over 2 weeks after the prMLC-2v-DsRed transfection. The prMLC-2v-DsRed was specifically expressed in the $Sca-1^+$ BMMSCs with cardiomyogenic lineage differentiation and it demonstrates that the 309 bp sequences of the rat MLC-2v 5'-flanking region is sufficient to confer cardiac specific expression on a DsRed reporter gene. The cardiac-specific promoter-driven reporter vector provides an important tool for the study of stem cell differentiation and cell replacement therapy in ischemic cardiomyopathy.