• Reproductive and Developmental Biology
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• 제33권4호
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• pp.263-271
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• 2009

Cardiovascular diseases (CVDs) are one of the most cause of death around the world and fields of interest for cardiac stem cells. Also, current use of terminally differentiated adult cardiomyocytes for CVDs has limited regenerative capacity therefore any significant cell loss may result in the development of progressive heart failure. Human embryonic stem cells (hESCs) derived from blastocyst-stage embryos spontaneously have ability to differentiate via embryo-like aggregates (endoderm, ectoderm and mesoderm) in vitro into various cell types including cardiomyocyte. However, most effective molecule or optimized condition which can induce cardiac differentiation of hESCs is rarely studied. In this study, we developed both spontaneous and inductive cardiomyocyte-like cells differentiation from hESCs by treatment of induced-factors, 5-azacytidine, BMP-4 and cardiogenol C. On the one hand, spontaneous and inductive cardiomyocyte-like cells showed that cardiac markers are expressed for further analysis by RT-PCR and immunocytochemistry. Interestingly, BMP-4 greatly improved homogeneous population of the cardiomyocyte-like cells from hESCs CHA15 and H09. In conclusion, we verified that spontaneously differentiated cells showed cardiac specific markers which characterize cardiac cells, treated extrinsic factors can manage cellular signals and found that hESCs can undergo differentiation into cardiomyocytes better than spontaneous group. This finding offers an insight into the inductive factor of differentiated cardiomyocytes and provides some helpful information that may offer the potential of cardiomyocytes derived from hESCs using extrinsic factors.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.1.1-1.10
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• 2018

Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.49-59
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• 2023

Metabolic syndrome (MetS) involves multi-factorial conditions linked to an elevated risk of type 2 diabetes mellitus and cardiovascular disease. Pre-metabolic syndrome (pre-MetS) possesses two MetS components but does not meet the MetS diagnostic criteria. Although cardiac autonomic derangements are evident in MetS, there is little information on their status in pre-MetS subjects. In this study, we sought to examine cardiac autonomic functions in pre-MetS and to determine which MetS component is more responsible for impaired cardiac autonomic functions. A total of 182 subjects were recruited and divided into healthy controls (n=89) and pre-MetS subjects (n=93) based on inclusion and exclusion criteria. We performed biochemical profiles on fasting blood samples to detect pre-MetS. Using standardized protocols, we evaluated anthropometric data, body composition, baroreflex sensitivity (BRS), heart rate variability (HRV), and autonomic function tests (AFTs). We further examined these parameters in pre-MetS subjects for each MetS component. Compared to healthy controls, we observed a significant cardiac autonomic dysfunction (CAD) through reduced BRS, lower overall HRV, and altered AFT parameters in pre-MetS subjects, accompanied by markedly varied anthropometric, clinical and biochemical parameters. Furthermore, all examined BRS, HRV, and AFT parameters exhibited an abnormal trend and significant correlation toward hyperglycemia. This study demonstrates CAD in pre-MetS subjects with reduced BRS, lower overall HRV, and altered AFT parameters. Hyperglycemia was considered an independent determinant of alterations in all the examined BRS, HRV, and AFT parameters. Thus, hyperglycemia may contribute to CAD in pre-MetS subjects before progressing to MetS.

• Journal of Chest Surgery
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• 제56권3호
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• pp.155-161
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• 2023

Background: Surgical closure of an atrial septal defect (ASD) is infrequently indicated during infancy. We evaluated the clinical characteristics and outcomes of patients who underwent surgical ASD closure during infancy. Methods: A single-center retrospective review was performed for 39 patients (19 males) who underwent surgical ASD closure during infancy between 1993 and 2020. The median body weight percentile at the time of operation was 9.3. Results: During a median follow-up of 60.9 months, 4 late deaths occurred due to chronic respiratory failure. A preoperative history of bronchopulmonary dysplasia (BPD) was the only risk factor for late mortality identified in Cox regression (hazard ratio, 3.54; 95% confidence interval [CI], 1.75-163.04; p=0.015). The 5-year survival rate was significantly lower in patients with preoperative history of BPD (97.0% vs. 50.0%, p<0.001) and preoperative ventilatory support (97.1% vs. 40.4%, p<0.001). There were significant postoperative increases in left ventricular end-diastolic (p=0.017), end-systolic (p=0.014), and stroke volume (p=0.013) indices. A generalized estimated equation model showed significantly better postoperative improvement in body weight percentiles in patients with lower weight percentiles at the time of operation (<10th percentile, p=0.01) and larger indexed ASD diameter (≥45 mm/m², p=0.025). Conclusion: Patients with ASD necessitating surgical closure during infancy are extremely small preoperatively and remain small even after surgical closure. However, postoperative somatic growth was more prominent in smaller patients with larger defects, which may be attributable to an increase in postoperative cardiac output due to changes in ventricular septal configuration. The benefits of ASD closure in patients with BPD are undetermined.

• Molecules and Cells
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• 제43권4호
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• pp.408-418
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• 2020

The sinus node (SN) is located at the apex of the cardiac conduction system, and SN dysfunction (SND)-characterized by electrical remodeling-is generally attributed to idiopathic fibrosis or ischemic injuries in the SN. SND is associated with increased risk of cardiovascular disorders, including syncope, heart failure, and atrial arrhythmias, particularly atrial fibrillation. One of the histological SND hallmarks is degenerative atrial remodeling that is associated with conduction abnormalities and increased right atrial refractoriness. Although SND is frequently accompanied by increased fibrosis in the right atrium (RA), its molecular basis still remains elusive. Therefore, we investigated whether SND can induce significant molecular changes that account for the structural remodeling of RA. Towards this, we employed a rabbit model of experimental SND, and then compared the genome-wide RNA expression profiles in RA between SND-induced rabbits and sham-operated controls to identify the differentially expressed transcripts. The accompanying gene enrichment analysis revealed extensive pro-fibrotic changes within 7 days after the SN ablation, including activation of transforming growth factor-β (TGF-β) signaling and alterations in the levels of extracellular matrix components and their regulators. Importantly, our findings suggest that periostin, a matricellular factor that regulates the development of cardiac tissue, might play a key role in mediating TGF-β-signaling-induced aberrant atrial remodeling. In conclusion, the present study provides valuable information regarding the molecular signatures underlying SND-induced atrial remodeling, and indicates that periostin can be potentially used in the diagnosis of fibroproliferative cardiac dysfunctions.

• Clinical and Experimental Pediatrics
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• 제53권6호
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• pp.680-687
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• 2010

Patients with congenital heart diseases (CHD) are confronted with early- and late-onset complications, such as conduction disorders, arrhythmias, myocardial dysfunction, altered coronary flow, and ischemia, throughout their lifetime despite successful hemodynamic and/or anatomical correction. Rhythm disturbance is a well-known and increasingly frequent cause of morbidity and mortality in patients with CHD. Predisposing factors to rhythm disturbances include underlying cardiac defects, hemodynamic changes as part of the natural history, surgical repair and related scarring, and residual hemodynamic abnormalities. Acquired factors such as aging, hypertension, diabetes, obesity, and others may also contribute to arrhythmogenesis in CHD. The first step in evaluating arrhythmias in CHD is to understand the complex anatomy and to find predisposing factors and hemodynamic abnormalities. A practical stepwise approach can lead to diagnosis and prompt appropriate interventions. Electrophysiological assessment and management should be done with integrated care of the underlying heart defects and hemodynamic abnormalities. Catheter ablation and arrhythmia surgery have been increasingly applied, showing increasing success rates with technological advancement despite complicated arrhythmia circuits in complex anatomy and the difficulty of access. Correction of residual hemodynamic abnormalities may be critical in the treatment of arrhythmia in patients with CHD.

• Reproductive and Developmental Biology
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• 제35권4호
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• pp.457-461
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• 2011

JAZF1 (Juxtaposed with Another Zinc Finger gene 1) transcription factor are Zn-finger proteins that bind to the nuclear orphan receptor TAK/TR4 (Nakajima et al., 2004). The nuclear orphan receptor TAK1/TR4 functions as a positive as well as a negative regulator of transcription. It was recently reported that congenital cardiovascular malformations are significantly more frequent in Neurofibromatosis 1 (NF1) patients with microdeletion syndrome than in those with classical NF1. JAZF1 was expressed in adult heart of patients with microdeletion syndrome. JAZF1 is highly conserved among various species include zebrafish. We hypothesized that the expression of zebrafish Jazf1 may lead to severe forms of congenital heart disease that allow the survival of newborns and adults. In this study, we created Jazf1 transgenic zebrafish which over-express zebrafish Jazf1 cDNA under control of the CMV promoter. Our results suggested that Jazf1 expression may play an important role in zebrafish cardiac development.

• Toxicological Research
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• 제35권3호
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• pp.233-239
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• 2019

Nerium oleander (N. oleander) is a well-known poisonous shrub that is frequently grown in gardens and public areas and contains numerous toxic compounds. The major toxic components are the cardiac glycosides oleandrin and neriin. The aim of our study was to evaluate the toxic effects of an ethanolic N. oleander leaf extract on haematological, cardiac, inflammatory, and serum biochemical parameters, as well as histopathological changes in the heart. N. oleander extract was orally administered for 14 and 30 consecutive days at doses of 100 and 200 mg of dried extract/kg of body weight in 0.5 mL of saline. The results showed significant increases in mean corpuscular volume, white blood cell counts, platelet counts, interleukins (IL-1 and IL-6), tumour necrosis factor alpha, C reactive protein, alanine aminotransferase, lactate dehydrogenase, creatine kinase and creatine kinase MB, especially at high doses. Marked pathological changes were perceived in the heart tissue. Thus, it can be concluded that exposure to N. oleander leaf extract adversely affects the heart and liver.

• 한국환경과학회지
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• 제23권5호
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• pp.793-800
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• 2014

This study was conducted to observe the influences of Crataegus pinnatifida BUNGE extract on lipid concentration in hypercholesterolemic rats (Sprague Dawley, male) fed the experimental diets for 5 weeks. Body weight gain was remarkably lower in the Crataegus pinnatifida BUNGE extract intake group than in the hypercholesterolemic rats. Total cholesterol concentration was remarkably lower in the extract of Crataegus pinnatifida BUNGE supplement in hypercholesterolemic rats than in the hypercholesterolemic model. Whereas, concentrations of HDL-cholesterol, ratio of HDL-cholesterol concentration to total cholesterol were remarkably higher in the extract of Crataegus pinnatifida BUNGE supplement in hypercholesterolemic rats than in the hypercholesterolemic model. Atherosclerotic index (AI), cardiac risk factor (CRF) were remarkably lower in the extract of Crataegus pinnatifida BUNGE supplement in hypercholesterolemic rats than in the hypercholesterolemic model. From the above research, Crataegus pinnatifida BUNGE extract was effective on the lipid concentrations in sera of dietary hypercholesterolemic rats.

• Journal of Chest Surgery
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• 제6권2호
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• pp.189-194
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• 1973

A cardiac injury is one of the most dramatic and demanding emergencies than may be cared by the surgeon. Four patients who sustained penetrating wound of the heart have been experienced in the Depart-ment of Thoracic Surgery, Kyungpook National University Hospital. They were 3 males and one female. The age was between 21 and 25. All of this series had stab wounds on the heart by instruments of scissors, gimlet, kitchen knife and glass. Injured sites were two cases of right ventricle, one of the right atrium and one of indifinitive with pericardial laceration. Three of these patients have been successfully treated by emergency thoracotomy with 3-0 silk sutures for myocardial penetrating wounds. One of these patients occurred cardiac arrest during surgery and expired, who was in penetrated right ventricular injury through which massive bleeded. The classic clinical description of tamponade, Beck`s triad, seemed to be useful for making diagnosis of the tamponade but not entirely reliable as diagnostic criterion of the tamponade. In the studing of 3 tamponade cases in these series, the triad of Beck was presented in only two cases. Elevated venous pressure was thought to be a valuable diagnostic factor in pericardial tamponade.