• Molecules and Cells
• /
• v.37 no.11
• /
• pp.785-794
• /
• 2014

Mitophagy, a cellular process that selectively targets dysfunctional mitochondria for degradation, is currently a hot topic in research into the pathogenesis and treatment of many human diseases. Considering that hypoxia causes mitochondrial dysfunction, which results in cell death, we speculated that selective activation of mitophagy might promote cell survival under hypoxic conditions. In the present study, we introduced the Regulator of calcineurin 1-1L (Rcan1-1L) to initiate the mitophagy pathway and aimed to evaluate the effect of Rcan1-1L-induced mitophagy on cell survival under hypoxic conditions. Recombinant adenovirus vectors carrying Rcan1-1L were transfected into human umbilical vein endothelial cells and human adult cardiac myocytes. Using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and Trypan blue exclusion assay, Rcan1-1L overexpression was found to markedly reverse cell growth inhibition induced by hypoxia. Additionally, Rcan1-1L overexpression inhibited cell apoptosis under hypoxic conditions, as detected by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis assay. Meanwhile, the mitochondria-mediated cell apoptotic pathway was inhibited by Rcan1-1L. In contrast, knockdown of Rcan1-1L accelerated hypoxia-induced cell apoptosis. Moreover, Rcan1-1L overexpression significantly reduced mitochondrial mass, decreased depolarized mitochondria, and downregulated ATP and reactive oxygen species production. We further delineated that the loss of mitochondrial mass was due to the activation of mitophagy induced by Rcan1-1L. Rcan1-1L overexpression activated autophagy flux and promoted translocation of the specific mitophagy receptor Parkin into mitochondria from the cytosol, whereas inhibition of autophagy flux resulted in the accumulation of Parkin-loaded mitochondria. Finally, we demonstrated that mitochondrial 1permeability transition pore opening was significantly increased by Rcan1-1L overexpression, which suggested that Rcan1-1L might evoke mitophagy through regulating mitochondrial permeability transition pores. Taken together, we provide evidence that Rcan1-1L overexpression induces mitophagy, which in turn contributes to cell survival under hypoxic conditions, revealing for the first time that Rcan1-1L-induced mitophagy may be used for cardioprotection.

• Genomics & Informatics
• /
• v.8 no.3
• /
• pp.108-115
• /
• 2010

Hypertension is the most prevalent disease worldwide and is itself a risk factor for cerebral, cardiac, and renal diseases. The inconsistency of candidate genes suggested by previous genomewide association studies (GWASs) may be due to not only differences in study design and genetic or environmental background but also the difference in the power of analysis between continuous traits and discrete traits. We analyzed 352,228 single nucleotide polymorphisms (SNPs) in 8842 unrelated Koreans obtained from Ansan and Ansung cohorts. We performed a series of GWA analyses using three different phenotype models; young hypertensive cases (278 subjects) versus elderly normotensive controls (680 subjects); the upper 25% (2211 hypertensive cases) versus the lower 25% of the SBP distribution (2211 hypotensive controls); and finally SBP and DBP as continuous traits (8842 subjects). The numbers of young hypertensive cases and elderly normotensive controls were not large enough to achieve genomewide significance. The model comparing the upper 25% subjects to the lower 25% of subjects showed a power that was approximate to that of QTL analysis. Two neighboring SNPs of the ATP2B1 gene, rs17249754 (SBP, p=$2.53^{-10}$; DBP, p=$1.28{\times}10^{-8}$) and rs7136259 (SBP, p=$1.30{\times}10^{-9}$; DBP, p=$6.41{\times}10^{-8}$), were associated with both SBP and DBP. Interestingly, a SNP of the RPL6 gene, rs11066280, revealed a significant genomewide association with SBP in men only (p=$3.85{\times}10^{-8}$), and four SNPs located near the MAN2A1 gene showed a strong association with DBP only in elderly men aged 60-70 years (e.g., rs6421827, p=$4.86{\times}10^{-8}$). However, we did not observe any gene variant attaining genomewide significance consistently in the three phenotype models except for the ATP2B1 gene variants. In general, the association signal with blood pressure was stronger in women than in men. Genes identified in GWASs are expected to open the way for prevention, early diagnosis, and personalized treatment of hypertension.

• Journal of Chest Surgery
• /
• v.45 no.5
• /
• pp.295-300
• /
• 2012

Background: With growing attention to the aortopathy associated with aortic valve diseases, the number of candidates for accompanying ascending aorta and/or root replacement is increasing among the patients who require aortic valve replacement (AVR). However, such procedures have been considered more risky than AVR alone. This study aimed to compare the surgical outcome of isolated AVR and AVR combined with aortic procedures. Materials and Methods: A total of 86 patients who underwent elective AVR between 2004 and June 2010 were divided into two groups: complex AVR (n=50, AVR with ascending aorta replacement in 24 and the Bentall procedure in 26) and simple AVR (n=36). Preoperative characteristics, surgical data, intra- and postoperative allogenic blood transfusion requirement, the postoperative clinical course, and major complications were retrospectively reviewed and compared. Results: The preoperative mean logistic European System for Cardiac Operative Risk Evaluation (%) did not differ between the groups: $11.0{\pm}7.8%$ in the complex AVR group and $12.3{\pm}8.0%$ in the simple AVR group. Although complex AVR required longer cardiopulmonary bypass ($152.4{\pm}52.6$ minutes vs. $109.7{\pm}22.7$ minutes, p=0.001), the quantity of allogenic blood products did not differ ($13.4{\pm}14.7$ units vs. $13.9{\pm}11.2$ units). There was no mortality, mechanical circulatory support, stroke, or renal failure requiring hemodialysis/filtration. No difference was found in the incidence of bleeding (40% vs. 33.3%) which was defined as red blood cell transfusion ${\geq}5$ units, reoperation, or intentional delayed closure. The incidence of mediastinitis (2.0% vs. 0%), ventilator ${\geq}24$ hours (4.0% vs. 2.8%), atrial fibrillation (18.0% vs. 25.0%), mean intensive care unit stay (34.5 hours vs. 38.8 hours), and median hospital stay (8 days vs. 7 days) did not differ, either. Conclusion: AVR combined with additional aortic or root replacement showed an excellent outcome and recovery course equivalent to that after isolated AVR.

• Journal of Clinical Nutrition
• /
• v.10 no.2
• /
• pp.45-50
• /
• 2018

Purpose: Intense multidisciplinary team effort is required for the intestinal rehabilitation of patients afflicted with the short bowel syndrome (SBS). These include enteral and parenteral nutrition (PN) support, monitoring of complications related to treatment, and considering further medical or surgical options for intestinal adaptation. Methods: In the Intestinal Rehabilitation Team (IRT) at the Samsung Medical Center, we have experienced 20 cases of adult SBS requiring multidisciplinary intestinal rehabilitation. This study is a retrospective review of the collected medical records. Results: Of the 20 subjects treated, 12 patients were male and 8 patients were female. At the time of referral to the IRT, the mean age was 51.5 years, and the mean body weight was 50.1 kg, which was 90% of the usual body weight. The diseases or operative managements preceding massive bowel resection were malignancy in 11 cases, cardiac surgery in 2 cases, trauma in 2 cases and one case, each of tuberculosis, corrosive esophagitis, atrial fibrillation, simultaneous pancreas and kidney transplantation, and perforated appendicitis. Of these, there were 14 survivals and 6 mortalities. The fatalities were attributed to progression of disease, intestinal failure-associated liver disease, and sepsis (unrelated to intestinal failure) (2 cases each). Among the 14 surviving patients, 8 patients have been weaned off PN, whereas 6 are still dependent on PN (mean PN dependence 36%). Conclusion: This paper reports the results of multidisciplinary intestinal rehabilitation of adult short bowel patients treated at the Samsung Medical Center. Further studies are required to improve survival and enteral tolerance of these patients.

• Journal of the Korean Society of Radiology
• /
• v.12 no.7
• /
• pp.869-877
• /
• 2018

This study analyzed the current status of MRI (frequency, amount of treatment) based on the history of application of the MRI health insurance benefit standard and health insurance claim data. MRI examinations began as a health insurance benefit in 2005. In 2005, the indications were restricted for some diseases, but coverage for benefits in 2010, 2013, 2016, and 2018 was expanded. In 2021, the Ministry of Health and Welfare decided to apply health insurance for all MRI examinations. From 2010 to 2017, the number of MRI examinations increased by 86.7% in 2017 compared to 2010, and the amount of treatment increased by 53.5%. According to general characteristics, the number of MRI examinations was higher in women than in men. By age, the number of examinations was the highest among ages 70-79. Outpatient examinations were more frequent than inpatient examinations, and the number of examinations in the tertiary hospitals was the highest among the types of hospitals. The number of brain MRI examinations was the highest in each exam site. In December 2013, the standard of MRI was expanded for heart disease and Crohn's disease, the number of cardiac MRI and abdominal MRI examinations increased in 2014 compared to 2013. However, the number of examinations is small and not associate with the disease, it would be difficult to say that it affected the increase in the total number of MRI examinations. To assess health insurance sustainability and policy effectiveness, monitoring will be necessary.

• Pediatric Infection and Vaccine
• /
• v.28 no.2
• /
• pp.66-81
• /
• 2021

The coronavirus disease 2019 pandemic has been continuously spreading throughout the world. As of July 15, 2021, there have been more than 188 million confirmed cases and more than 4.06 million deaths. Although the incidence of severe infections is relatively low in children and adolescents compared to adults, a complication called multisystem inflammatory syndrome in children (MIS-C) may occur in some cases at approximately 2-6 weeks after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. MIS-C can be seen in patients of various ages, from young infants to adolescents, and may present with diverse clinical manifestations. While fever present in a great majority of patients, symptoms suggesting the involvement of the digestive or nervous system and the skin and mucous membranes (Kawasaki disease-like symptoms) also appear in many cases. Cardiac involvement may also be observed, including left ventricular dysfunction, myocarditis, coronary artery dilatation, and coronary aneurysm. In some cases, hypotension or shock can occur, and mechanical ventilation or treatment in the intensive care unit may be necessary. Fortunately, recovery is generally reported after appropriate treatment. MIS-C is a rare but important complication of SARS-CoV-2 infection in children and adolescents. As such, it is important to recognize the clinical symptoms and provide appropriate treatment at an early stage. In this review, the epidemiology, clinical symptoms, suggested pathophysiology, diagnostic approach, and treatment of MIS-C will be discussed.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.21 no.1
• /
• pp.22-27
• /
• 2021

Propionic acidemia (PA) is an inherited autosomal recessive disorder, due to the deficiency of propionyl-CoA carboxylase (PCC). PCC is the enzyme which catalyzes the conversion of propionyl-CoA to D-methylmalonyl-CoA, and it is critical for the metabolism of amino acids, odd-chain fatty acids, and side chains of cholesterol. The clinical manifestations present mostly at the neonatal period with life-threatening metabolic acidosis and hyperammonemia. Here, we described a case of a 16-year-old Korean boy with late-onset PA who presented with embolic cerebral infarction due to dilated cardiomyopathy (DCMP) with left ventricular noncompaction. And he has family history of sudden cardiac death, so we performed metabolic screening and genetic tests. Elevated levels of 3-hydroxypropionic acid, methylcitric acid and propionylglycerine were detected in urine. Plasma acylcarnitine profile showed elevated propionylcarnitine (C3). Diagnosis of PA was confirmed by genetic analysis, which revealed compound heterozygous mutations, c.[1151T>G] (p.[Phe384Cys]) and c.[1228C>T] (p.[Arg410Trp]) in PCCB gene. His heart function is in improving state and the results of biochemical analysis are stable with heart failure medication and metabolic managements. We present a case of patient without episodes of metabolic decompensation who manifests DCMP as the first symptom of PA.

• Journal of Life Science
• /
• v.33 no.1
• /
• pp.64-72
• /
• 2023

Despite several advances in identification of cardiac transcription factors, there are still needs to find new bioactive molecules that promote cardiomyogenesis from stem cells to highly efficient myocardial differentiation. We analyzed Illumina expression microarray data of mouse embryonic stem cells (mESCs)-derived cardiomyocytes. 276 genes were upregulated (≥ 4fold) in mESCs-derived cardiomyocytes compared undifferentiated ESCs. Secreted phosphoprotein 2 (Spp2) is one of candidates and is known to inhibit bone morphogenetic protein 2 (BMP2) signal transduction as a pseudoreceptor for BMP2. However, its function in cardiomyogenesis is unknown. We confirmed that Spp2 expression increased during the differentiation into functional cardiomyocytes using mESCs, TC-1/Kh2 and E14. Interestingly, Spp2 secretion transiently increased 3 days after formation of embryoid bodies (EBs), indicating that the extracellular secretion of Spp2 is involved in the differentiation of ESCs into cardiomyocytes. To characterize Spp2, we performed experiments using the C2C12 mouse myoblast cell line, which has the property of shifting the differentiation pathway from myoblastic to osteoblastic by treatment with BMP2. Similar to the differentiation of ESCs, transcription of Spp2 increased as C2C12 myoblasts differentiated into myotubes. In particular, Spp2 secretion increased dramatically in the early stage of differentiation. Furthermore, treatment with Spp2-Flag recombinant protein promoted the differentiation of C2C12 myoblasts into myotubes. Taken together, we suggest a novel bioactive protein Spp2 that differentiates ESCs into cardiomyocytes. This may be useful for understanding the molecular pathways of cardiomyogenesis and for experimental or clinical promotion of stem cell therapy for ischemic heart diseases.

• Journal of Korean Clinical Nursing Research
• /
• v.29 no.1
• /
• pp.24-41
• /
• 2023

Purpose: This study aimed to update the previously published nursing practice guideline for prevention of venous thromboembolism (VTE). Methods: The guideline was updated according to the manuals developed by National Institute for Health and Care Excellence (NICE) and Scottish Intercollegiate Guidelines Network (SIGN), and a Handbook for Clinical Practice Guideline Developer Version 10. Results: The updated nursing practice guideline for prevention of VTE was consisted of 16 domains, 46 subdomains, and 216 recommendations. The recommendations in each domain were: 4 general issues, 8 assessment of risk and bleeding factors, 5 interventions for prevention of VTE, 18 mechanical interventions, 36 pharmacological interventions, 36 VTE prevention starategies for medical patients, 25 for cancer patients, 13 for pregnancy, 8 for surgical patients, 7 for thoractic and cardiac surgery, 16 for orthopedic surgery, 10 for cranial and spinal surgery, 5 for vascular surgery, 13 for other surgery, 3 educations and information, and 2 documentation and report. For these recommendations, the level of evidence was 32.1% for level I, 51.8% for level II, and 16.1% for level III according to the infectious diseases society of America (IDSA) rating system. A total of 112 new recommendations were developed and 49 previous recommendations were deleted. Conclusion: The updated nursing practice guideline for prevention of VTE is expected to serve as an evidence-based practice guideline for prevention of VTE in South Korea. It is recommended that this guideline will disseminate to clinical nursing settings nationwide to improve the effectiveness of prevention of VTE practice.

• Genomics & Informatics
• /
• v.20 no.4
• /
• pp.44.1-44.13
• /
• 2022

Brugada syndrome (BS) is an autosomal dominant inheritance cardiac arrhythmia disorder associated with sudden death in young adults. Thailand has the highest prevalence of BS worldwide, and over 60% of patients with BS still have unclear disease etiology. Here, we performed a new viral metagenome analysis pipeline called VIRIN and validated it with whole genome sequencing (WGS) data of HeLa cell lines and hepatocellular carcinoma. Then the VIRIN pipeline was applied to identify viral integration positions from unmapped WGS data of Thai males, including 100 BS patients (case) and 100 controls. Even though the sample preparation had no viral enrichment step, we can identify several virus genes from our analysis pipeline. The predominance of human endogenous retrovirus K (HERV-K) viruses was found in both cases and controls by blastn and blastx analysis. This study is the first report on the full-length HERV-K assembled genomes in the Thai population. Furthermore, the HERV-K integration breakpoint positions were validated and compared between the case and control datasets. Interestingly, Brugada cases contained HERV-K integration breakpoints at promoters five times more often than controls. Overall, the highlight of this study is the BS-specific HERV-K breakpoint positions that were found at the gene coding region "NBPF11" (n = 9), "NBPF12" (n = 8) and long non-coding RNA (lncRNA) "PCAT14" (n = 4) region. The genes and the lncRNA have been reported to be associated with congenital heart and arterial diseases. These findings provide another aspect of the BS etiology associated with viral genome integrations within the human genome.