Association of epicardial fat with left ventricular diastolic function in subjects with metabolic syndrome: assessment using 2-dimensional echocardiography

Background Metabolic syndrome (MetS) is related with left ventricular diastolic dysfunction (LVDD) and poor cardiovascular outcome. Epicardial adipose tissue (EAT) thickness, measured by echocardiography, is increased in subjects with MetS. However, the association of EAT with LV diastolic function has not been evaluated in subjects with MetS. Methods In this retrospective study, EAT thickness was measured in 1,486 consecutive asymptomatic patients with no known heart disease who had transthoracic echocardiography during a self-referred healthcare exam. Subjects with a history of ischemic heart disease, cardiomyopathy or significant valvular heart disease were excluded. LVDD was defined as E/e ratio ≥ 15. Subjects were grouped into two groups, those with MetS and those without. Results MetS was present in 346 subjects. There was no difference in LV systolic function between the two groups. However compared to patients without MetS, patients with MetS had larger left atrium (LA) size and higher E/e ratio (38 ± 5 versus 35 ± 5 mm for LA and 10.0 ± 3.3 versus 8.7 ± 2.7 for E/e ratio in subjects with versus without MetS both p < 0.001). LVDD was found in 27 (7.8%) subjects with MetS, compared to 30 (2.6%) subjects without MetS (p < 0.001). In subjects with MetS, EAT was significantly correlated with LVDD, even after adjusting for other cardiometabolic risk factors such as age, systolic blood pressure, BMI, blood glucose and LDL cholesterol (OR 1.845, 95% CI 1.153-2.951, p = 0.011).This study was supported by Seoul National University Hospital (0420100700, 2010–1096).Peer Reviewe

Alpha-tocopherol exerts protective function against the mucotoxicity of particulate matter in amphibian and human goblet cells

Exposure to particulate matter (PM) in ambient air is known to increase the risk of cardiovascular disorders and mortality. The cytotoxicity of PM is mainly due to the abnormal increase of reactive oxygen species (ROS), which damage cellular components such as DNA, RNA, and proteins. The correlation between PM exposure and human disorders, including mortality, is based on long-term exposure. In this study we have investigated acute responses of mucus-secreting goblet cells upon exposure to PM derived from a heavy diesel engine. To this end, we employed the mucociliary epithelium of amphibian embryos and human Calu-3 cells to examine PM mucotoxicity. Our data suggest that acute exposure to PM significantly impairs mucus secretion and results in the accumulation of mucus vesicles in the cytoplasm of goblet cells. RNA-seq analysis revealed that acute responses to PM exposure significantly altered gene expression patterns; however, known regulators of mucus production and the secretory pathway were not significantly altered. Interestingly, pretreatment with alpha-tocopherol nearly recovered the hyposecretion of mucus from both amphibian and human goblet cells. We believe this study demonstrates the mucotoxicity of PM and the protective function of alpha-tocopherol on mucotoxicity caused by acute PM exposure from heavy diesel engines

The effect of non-optimal lipids on the progression of coronary artery calcification in statin-naïve young adults: results from KOICA registry

BackgroundDespite the importance of attaining optimal lipid levels from a young age to secure long-term cardiovascular health, the detailed impact of non-optimal lipid levels in young adults on coronary artery calcification (CAC) is not fully explored. We sought to investigate the risk of CAC progression as per lipid profiles and to demonstrate lipid optimality in young adults.MethodsFrom the KOrea Initiative on Coronary Artery calcification (KOICA) registry that was established in six large volume healthcare centers in Korea, 2,940 statin-naïve participants aged 20–45 years who underwent serial coronary calcium scans for routine health check-ups between 2002 and 2017 were included. The study outcome was CAC progression, which was assessed by the square root method. The risk of CAC progression was analyzed according to the lipid optimality and each lipid parameter.ResultsIn this retrospective cohort (mean age, 41.3 years; men 82.4%), 477 participants (16.2%) had an optimal lipid profile, defined as triglycerides &lt;150 mg/dl, LDL cholesterol &lt;100 mg/dl, and HDL cholesterol &gt;60 mg/dl. During follow-up (median, 39.7 months), CAC progression was observed in 434 participants (14.8%), and more frequent in the non-optimal lipid group (16.5% vs. 5.7%; p &lt; 0.001). Non-optimal lipids independently increased the risk of CAC progression [adjusted hazard ratio (aHR), 1.97; p = 0.025], in a dose-dependent manner. Even in relatively low-risk participants with an initial calcium score of zero (aHR, 2.13; p = 0.014), in their 20 s or 30 s (aHR 2.15; p = 0.041), and without other risk factors (aHR 1.45; p = 0.038), similar results were demonstrable. High triglycerides had the greatest impact on CAC progression in this young adult population.ConclusionNon-optimal lipid levels were significantly associated with the risk of CAC progression in young adults, even at low-risk. Screening and intervention for non-optimal lipid levels, particularly triglycerides, from an early age might be of clinical value

Real-Time Monitoring of Neural Differentiation of Human Mesenchymal Stem Cells by Electric Cell-Substrate Impedance Sensing

Stem cells are useful for cell replacement therapy. Stem cell differentiation must be monitored thoroughly and precisely prior to transplantation. In this study we evaluated the usefulness of electric cell-substrate impedance sensing (ECIS) for in vitro real-time monitoring of neural differentiation of human mesenchymal stem cells (hMSCs). We cultured hMSCs in neural differentiation media (NDM) for 6 days and examined the time-course of impedance changes with an ECIS array. We also monitored the expression of markers for neural differentiation, total cell count, and cell cycle profiles. Cellular expression of neuron and oligodendrocyte markers increased. The resistance value of cells cultured in NDM was automatically measured in real-time and found to increase much more slowly over time compared to cells cultured in non-differentiation media. The relatively slow resistance changes observed in differentiating MSCs were determined to be due to their lower growth capacity achieved by induction of cell cycle arrest in G0/G1. Overall results suggest that the relatively slow change in resistance values measured by ECIS method can be used as a parameter for slowly growing neural-differentiating cells. However, to enhance the competence of ECIS for in vitro real-time monitoring of neural differentiation of MSCs, more elaborate studies are needed

Potentiated therapeutic angiogenesis by primed human mesenchymal stem cells in a mouse model of hindlimb ischemia

Background: Human bone marrow-derived mesenchymal stem cells (hMSCs) are advantageous for cell-based therapy to treat ischemic diseases owing to their capacity to secrete various paracrine factors with potent angiogenic activity. Materials methods: In this study, we describe a method to increase secreted levels of VEGF and HGF from hMSCs without genetic modification. Results: We demonstrated that transplantation of primed hMSCs into ischemic limbs led to significantly greater improvements in tissue perfusion and limb salvage by increasing capillary formation compared with nonprimed hMSCs. The primed hMSCs also exhibited greater survival in vivo and secreted human VEGF and HGF in the ischemic tissue, supporting enhanced angiogenesis and cell survival. Conclusion: These findings indicate that priming hMSCs via methods described in this study enhances secretion of critical proangiogenic factors resulting in an enhanced therapeutic effect of cells for the treatment of ischemic diseases.This research was supported by grants from the Korea Health Technology R&D Project (M-S Chang, A100823) and the Innovative Research Institute for Cell Therapy, National University Hospital (A062260), both sponsored by the Ministry of Health, Welfare and Family, Seoul, Republic of Korea.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000027724/1SEQ:1PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000027724ADJUST_YN:YEMP_ID:A075930DEPT_CD:862CITE_RATE:3.718FILENAME:첨부된 내역이 없습니다.DEPT_NM:치의과학과EMAIL:[email protected]_YN:YCONFIRM:

Retrospective Analysis of Peripheral Blood Stem Cell Transplantation for the Treatment of High-Risk Neuroblastoma

Disease relapse after autologous peripheral blood stem cell transplantation (APBSCT) is the main cause of treatment failure in high-risk neuroblastoma (NBL). To reduce relapse, various efforts have been made such as CD34+ selection and double APBSCT. Here the authors reviewed the clinical features and outcomes of high-risk NBL patients and analyzed their survival. The medical records of 36 patients with stage III or IV NBL who underwent APBSCT at Seoul National University Children's Hospital between May 1996 and May 2004 were reviewed. Total 46 APBSCTs were performed in 36 patients. Disease free survival (DFS) and overall survival of all patients were 47.7% and 68.8%, respectively. The patients were allocated to three groups according to the APBSCT type. The DFS of CD34+ non-selected single APBSCT patients (N=13), CD34+ selected single APBSCT patients (N=14), and CD34+ selected double APBSCT patients (N=9) were 55.6%, 40.6%, and 50.0%, respectively, which were not significantly different. Thus the survival was not found to be affected by CD34+ selection or transplantation number. To improve long-term survival, various efforts should be made such as chemotherapy dose intensification, more effective tumor purging, and control of minimal residual disease via the use of differentiating and immune-modulating agents

Improved survival in patients with recurrent Wilms tumor: the experience of the Seoul National University Children's Hospital

The survival in cases with relapsed Wilms tumor is dismal. Recently, however the introduction of new therapeutic agents and experimental strategies has improved the survival. We analysed the survival of patients with relapsed Wilms tumor according to the treatment period. During the early period 1983-1993, patients who had received two drugs were treated with doxorubicin and the others were treated with cisplatin and etoposide, whereas during the late period 1994-2004, patients were treated with combinations of cyclophosphamide/etoposide and carboplatin/etoposide. During the early period, 8 of 57 experienced relapse, and 8 of 41 relapsed during the late period. Only 2 patients treated during the early period survived in complete response (CR), whereas during the late period, 5 patients remained alive in CR, and 3 of those received high-dose chemotherapy (HDC) with autologous peripheral stem cell rescue (SCR). The estimated 5 yr event-free survival rate was 37.5% in the entire study group, 50% for patients in the late period, and 25% for patients in the early period (p=0.38). The survival in patients with relapsed Wilms tumor dramatically improved during the late period and HDC with SCR was one of the effective salvage strategies

Air-stable n-type operation of Gd-contacted carbon nanotube field effect transistors

We report air-stable n -type operations of the single-walled carbon nanotube field effect transistors (SWNT-FETs) fabricated with Gd electrodes. Unlike previously reported n -type SWNT-FETs, our devices maintained their n -type operation characteristics in ambient atmosphere for more than two months. The shallow Gd films with a thickness below 20 nm are corroded by environmental oxygen, whereas the well-contacted Gd-SWNT interfaces underneath the thick Gd layers are protected from contaminations by air molecules. Theoretical studies based on the first-principles electronic structure calculations confirm that Gd layers have an excellent binding affinity to the SWNTs.open8

Polymorphisms in Apoptosis-Related Genes and TP53 Mutations in Non-Small Cell Lung Cancer

Apoptosis plays an essential role in the elimination of mutated or transformed cells from the body. Therefore, polymorphisms of apoptosis-related genes may lead to an alteration in apoptotic capacity, thereby affecting the occurrence of TP53 mutations in lung cancer. We investigated the relationship between potentially functional polymorphisms of apoptosis-related genes and TP53 mutations in non-small cell lung cancer (NSCLC). Twenty-seven single nucleotide polymorphisms in 20 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay in 173 NSCLCs and the associations with TP53 mutations in the entire coding exons (exons 2-11), including splicing sites of the gene, were analyzed. None of the 27 polymorphisms was significantly associated with the occurrence of TP53 mutations. This suggests that apoptosis-related genes may not play an important role in the occurrence of TP53 mutations in lung cancer