• Journal of Ginseng Research
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• v.47 no.6
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• pp.755-765
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• 2023

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca²⁺ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca²⁺ ([Ca²⁺]_i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca²⁺]_i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca²⁺]_i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca²⁺]_i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca²⁺ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca²⁺]_i.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.209-217
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• 2024

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.

• Journal of Korean Neurosurgical Society
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• v.67 no.4
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• pp.442-450
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• 2024

Objective : Cerebral hyperperfusion syndrome (CHS) manifests as a collection of symptoms brought on by heightened focal cerebral blood flow (CBF), afflicting nearly 30% of patients who have undergone superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis. The aim of this study was to investigate whether the amalgamation of magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) and apparent diffusion coefficient (ADC) imaging via MRI can discern cerebral hyperemia after STA-MCA anastomosis surgery. Methods : A retrospective study was performed of patients who underwent STA-MCA anastomosis due to Moyamoya disease or atherosclerotic steno-occlusive disease. A protocol aimed at preventing CHS was instituted, leveraging the use of MRI FLAIR. Patients underwent MRI diffusion with FLAIR imaging 24 hours after STA-MCA anastomosis. A high signal on FLAIR images signified the presence of hyperemia at the bypass site, triggering a protocol of hyperemia care. All patients underwent hemodynamic evaluations, including perfusion MRI, single-photon emission computed tomography (SPECT), and digital subtraction angiography, both before and after the surgery. If a high signal intensity is observed on MRI FLAIR within 24 hours of the surgery, a repeat MRI is performed to confirm the presence of hyperemia. Patients with confirmed hyperemia are managed according to a protocol aimed at preventing further progression. Results : Out of a total of 162 patients, 24 individuals (comprising 16 women and 8 men) exhibited hyperemia on their MRI FLAIR scans following the procedure. SPECT was conducted on 23 patients, and 11 of them yielded positive results. All 24 patients underwent perfusion MRI, but nine of them showed no significant findings. Among the patients, 10 displayed elevations in both CBF and cerebral blood volume (CBV), three only showed elevation in CBF, and two only showed elevation in CBV. Follow-up MRI FLAIR scans conducted 6 months later on these patients revealed complete normalization of the previously observed high signal intensity, with no evidence of ischemic injury. Conclusion : The study determined that the use of MRI FLAIR and ADC mapping is a competent means of early detection of hyperemia after STA-MCA anastomosis surgery. The protocol established can be adopted by other neurosurgical institutions to enhance patient outcomes and mitigate the hazard of permanent cerebral injury caused by cerebral hyperemia.

• Korean Circulation Journal
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• v.53 no.7
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• pp.425-451
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• 2023

Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, longterm anticoagulants are recommended according to the CHA₂DS₂-VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.

• Journal of the Korean Society of Radiology
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• v.83 no.4
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• pp.887-897
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• 2022

Purpose To evaluate the safety and efficacy of stent-assisted coil embolization (SAC) in acutely ruptured cerebral aneurysms without severe symptoms, and thus, the usefulness of the stent itself in patients with subarachnoid hemorrhages. Materials and Methods From January 2017 to June 2019, 118 patients were treated with coil embolization for acutely ruptured cerebral aneurysms without severe symptoms (Hunt & Hess grade ≤ 3). The periprocedural complications, six-month modified Rankin scores (mRS), and six-month radiologic outcomes were compared between 56 patients with SAC and 62 patients without SAC (non-SAC). Results The rate of good clinical outcomes (mRS ≤ 2), as well as the rate of hemorrhagic and ischemic complications, showed no significant difference between the SAC and non-SAC groups. Moreover, compared to the non-SAC group, the SAC group showed a lower recanalization rate on the six-month follow-up angiogram (20% vs. 39.3%, p = 0.001). Conclusion Although stent use was not significantly associated with clinical outcomes in coil embolization of ruptured cerebral aneurysms with non-severe symptoms (Hunt & Hess grade ≤ 3), it significantly decreased the rate of recanalization on follow-up cerebral angiograms.

• Korean Journal of Radiology
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• v.23 no.8
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• pp.828-834
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• 2022

Objective: This study aimed to assess the outcomes of outpatient day-care management of unruptured intracranial aneurysm (UIA), and to present the risks associated with different management strategies by comparing the outcomes and adverse events between outpatient day-care management and management with longer admission periods. Materials and Methods: This retrospective cohort study used prospectively registered data and was approved by a local institutional review board. We enrolled 956 UIAs from 811 consecutive patients (mean age ± standard deviation, 57 ± 10.7 years; male:female = 247:564) from 2017 to 2020. We compared the outcomes after embolization among the different admission-length groups (1, 2, and ≥ 3 days). The outcomes included pre- and post-modified Rankin Scale (mRS) scores and rates of adverse events, cure, recurrence, and reprocedure. Events were defined as any cerebrovascular problems, including minor and major stroke, death, or hemorrhage. Results: The mean admission period was 2 days, and 175 patients (191 aneurysms), 551 patients (664 aneurysms), and 85 patients (101 aneurysms) were discharged on the day of the procedure, day 2, and day 3 or later, respectively. During the mean 17-month follow-up period (range 6-53 months; 2757 patient years), no change in post-mRS was observed compared to pre-mRS in 99.6% of patients. Cure was achieved in 95.6% patients; minimal recurrence that did not require re-procedure occurred in 3.5% patients, and re-procedure was required in 2.3% (22 of 956) patients due to progressive enlargement of the recurrent sac during follow up (mean 17 months, range, 6-53 months). There were eight adverse events (0.8%), including five cerebrovascular (two major stroke, two minor strokes and one transient ischemic stroke), and three non-cerebrovascular events. Statistical comparison between groups with different admission lengths (1, 2, and ≥ 3 days) revealed no difference in the outcomes. Conclusion: This study revealed no difference in outcomes and adverse events according to the admission period, and suggested that UIA could be managed by outpatient day-care embolization.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.281-292
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• 2023

Background and Objectives: Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM) hold great promise as a cellular source of CM for cardiac function restoration in ischemic heart disease. However, the use of animal-derived xenogeneic substances during the biomanufacturing of hiPSC-CM can induce inadvertent immune responses or chronic inflammation, followed by tumorigenicity. In this study, we aimed to reveal the effects of xenogeneic substances on the functional properties and potential immunogenicity of hiPSC-CM during differentiation, demonstrating the quality and safety of hiPSC-based cell therapy. Methods and Results: We successfully generated hiPSC-CM in the presence and absence of xenogeneic substances (xeno-containing (XC) and xeno-free (XF) conditions, respectively), and compared their characteristics, including the contractile functions and glycan profiles. Compared to XC-hiPSC-CM, XF-hiPSC-CM showed early onset of myocyte contractile beating and maturation, with a high expression of cardiac lineage-specific genes (ACTC1, TNNT2, and RYR2) by using MEA and RT-qPCR. We quantified N-glycolylneuraminic acid (Neu5Gc), a xenogeneic sialic acid, in hiPSC-CM using an indirect enzyme-linked immunosorbent assay and liquid chromatography-multiple reaction monitoring-mass spectrometry. Neu5Gc was incorporated into the glycans of hiPSC-CM during xeno-containing differentiation, whereas it was barely detected in XF-hiPSC-CM. Conclusions: To the best of our knowledge, this is the first study to show that the electrophysiological function and glycan profiles of hiPSC-CM can be affected by the presence of xenogeneic substances during their differentiation and maturation. To ensure quality control and safety in hiPSC-based cell therapy, xenogeneic substances should be excluded from the biomanufacturing process.

• Journal of Korean Neurosurgical Society
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• v.67 no.1
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• pp.73-83
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• 2024

Objective : The Act on Life-Sustaining Treatment (LST) decisions for end-of-life patients has been effective since February 2018. An increasing number of patients and their families want to withhold or withdraw from LST when medical futility is expected. This study aimed to investigate the status of the Act on LST decisions for patients with acute cerebrovascular disease at a single hospital. Methods : Between January 2017 and December 2021, 227 patients with acute cerebrovascular diseases, including hemorrhagic stroke (n=184) and ischemic stroke (n=43), died at the hospital. The study period was divided into the periods before and after the Act. Results : The duration of hospitalization decreased after the Act was implemented compared to before (15.9±16.1 vs. 11.2±18.6 days, p=0.127). The rate of obtaining consent for the LST plan tended to increase after the Act (139/183 [76.0%] vs. 27/44 [61.4%], p=0.077). Notably, none of the patients made an LST decision independently. Ventilator withdrawal was more frequently performed after the Act than before (52/183 [28.4%] vs. 0/44 [0%], p<0.001). Conversely, the rate of organ donation decreased after the Act was implemented (5/183 [2.7%] vs. 6/44 [13.6%], p=0.008). Refusal to undergo surgery was more common after the Act was implemented than before (87/149 [58.4%] vs. 15/41 [36.6%], p=0.021) among the 190 patients who required surgery. Conclusion : After the Act on LST decisions was implemented, the rate of LST withdrawal increased in patients with acute cerebrovascular disease. However, the decision to withdraw LST was made by the patient's family rather than the patient themselves. After the execution of the Act, we also observed an increased rate of refusal to undergo surgery and a decreased rate of organ donation. The Act on LST decisions may reduce unnecessary treatments that prolong end-of-life processes without a curative effect. However, the widespread application of this law may also reduce beneficial treatments and contribute to a decline in organ donation.

• Korean Journal of Radiology
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• v.21 no.9
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• pp.1055-1064
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• 2020

Objective: To assess the incremental prognostic value of coronary computed tomography angiography (CCTA) in comparison to a clinical risk model (Framingham risk score, FRS) and coronary artery calcium score (CACS) for future cardiac events in ischemic stroke patients without chest pain. Materials and Methods: This retrospective study included 1418 patients with acute stroke who had no previous cardiac disease and underwent CCTA, including CACS. Stenosis degree and plaque types (high-risk, non-calcified, mixed, or calcified plaques) were assessed as CCTA variables. High-risk plaque was defined when at least two of the following characteristics were observed: low-density plaque, positive remodeling, spotty calcification, or napkin-ring sign. We compared the incremental prognostic value of CCTA for major adverse cardiovascular events (MACE) over CACS and FRS. Results: The prevalence of any plaque and obstructive coronary artery disease (CAD) (stenosis ≥ 50%) were 70.7% and 30.2%, respectively. During the median follow-up period of 48 months, 108 patients (7.6%) experienced MACE. Increasing FRS, CACS, and stenosis degree were positively associated with MACE (all p < 0.05). Patients with high-risk plaque type showed the highest incidence of MACE, followed by non-calcified, mixed, and calcified plaque, respectively (log-rank p < 0.001). Among the prediction models for MACE, adding stenosis degree to FRS showed better discrimination and risk reclassification compared to FRS or the FRS + CACS model (all p < 0.05). Furthermore, incorporating plaque type in the prediction model significantly improved reclassification (integrated discrimination improvement, 0.08; p = 0.023) and showed the highest discrimination index (C-statistics, 0.85). However, the addition of CACS on CCTA with FRS did not add to the prediction ability for MACE (p > 0.05). Conclusion: Assessment of stenosis degree and plaque type using CCTA provided additional prognostic value over CACS and FRS to risk stratify stroke patients without prior history of CAD better.

• Journal of Cardiovascular Imaging
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• v.31 no.1
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• pp.51-61
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• 2023

BACKGROUND: Valvular heart disease (VHD) is a common cause of cardiovascular morbidity and mortality worldwide; however, its epidemiological profile in Korea requires elucidation. METHODS: In this nationwide retrospective cohort study from the Korean valve survey, which collected clinical and echocardiographic data on VHD from 45 medical centers, we identified 4,089 patients with VHD between September and October 2019. RESULTS: The aortic valve was the most commonly affected valve (n = 1,956 [47.8%]), followed by the mitral valve (n = 1,598 [39.1%]) and tricuspid valve (n = 1,172 [28.6%]). There were 1,188 cases of aortic stenosis (AS) and 926 cases of aortic regurgitation. The most common etiology of AS was degenerative disease (78.9%). The proportion of AS increased with age and accounted for the largest proportion of VHD in patients aged 80-89 years. There were 1,384 cases of mitral regurgitation (MR) and 244 cases of mitral stenosis (MS). The most common etiologies for primary and secondary MR were degenerative disease (44.3%) and non-ischemic heart disease (63.0%), respectively, whereas rheumatic disease (74.6%) was the predominant cause of MS. There were 1,172 tricuspid regurgitation (TR) cases, of which 46.9% were isolated and 53.1% were associated with other valvular diseases, most commonly with MR. The most common type of TR was secondary (90.2%), while primary accounted for 6.1%. CONCLUSIONS: This report demonstrates the current epidemiological status of VHD in Korea. The results of this study can be used as fundamental data for developing Korean guidelines for VHD.