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1.
J Bone Miner Metab ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34626249

RESUMO

INTRODUCTION: Many previous studies have reported a positive relationship between alcohol and bone mineral density (BMD). However, the causality between alcohol and BMD has not been fully evaluated. MATERIALS AND METHODS: This study enrolled 8892 participants from the Dong-gu study. Mendelian randomization (MR) using two-stage least-squared regression was used to evaluate the association between the genetically predicted amount of alcohol consumption per day and BMD. The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as instrumental variables for alcohol consumption. Age, smoking history, and BMI were adjusted in the multivariate model. RESULTS: Self-reported alcohol consumption was positively related to total hip and lumbar spine BMD in both sexes. In multivariate Mendelian randomization analysis, the genetically predicted amount of alcohol consumption was positively associated with both total hip and lumbar spine BMD in men. Total hip BMD and lumbar spine BMD increased by 0.004 g/cm2 (95% confidence interval [CI] 0.002-0.007) and 0.007 g/cm2 (95% CI 0.004-0.011) with doubling of alcohol consumption. However, in women, genetically predicted alcohol consumption was not significantly associated with BMD. CONCLUSION: In our MR study, genetically predicted alcohol consumption was positively associated with BMD in men. This result suggests that the association between alcohol consumption and BMD is causal.

2.
BMJ Open ; 11(10): e052059, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716164

RESUMO

OBJECTIVE: This study aimed to investigate the nutritional status of children and adolescents from North Korean defector (NKD) families who are currently living in South Korea (SK) and compared with the status of those from SK families. DESIGN: A cross-sectional study comparing the prevalence of malnutrition, overweight and obesity between children and adolescents from NKD families and SK families. SETTING: Children and adolescents from NKD families were interviewed face-to-face directly, whereas the data about those from SK families acquired by using 2017 Korea National Health and Nutrition Examination Survey. Their nutritional status were estimated using the 2017 Korean National Growth Charts for children and adolescents. PARTICIPANTS: The total number of children and adolescents was 2136 consisting of 527 subjects from the NKD families and 1609 subjects from the SK families. RESULTS: The overall prevalence of stunting, wasting, underweight, overweight and obesity in NKD group was 8.9%, 10.2%, 10.4%, 11.2% and 12.2% respectively, and 1.9%, 7.1%, 5.9%, 9.2% and 9.3%, respectively, in SK families. The NKD group showed significantly higher prevalence than SK group in stunting (p<0.001), wasting (p=0.014), underweight (p<0.001), obesity (p=0.041) but not in overweight. CONCLUSIONS: The nutritional status of children and adolescents form NKD families was worse than that of those from SK families, and also higher prevalence of obesity.


Assuntos
Estado Nutricional , Magreza , Adolescente , Criança , Estudos Transversais , Transtornos do Crescimento/epidemiologia , Humanos , Inquéritos Nutricionais , Prevalência , República da Coreia/epidemiologia , Magreza/epidemiologia
3.
Clin Transl Sci ; 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719115

RESUMO

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08-3.29), bradycardia (aOR: 2.09, 95% CI: 1.24-3.53), and hypotension (aOR: 1.67, 95% CI: 1.03-2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.

4.
J Korean Med Sci ; 36(30): e195, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34342185

RESUMO

BACKGROUND: Several studies have reported conflicting results regarding the relationship between alcohol consumption and cortisol levels. However, the causality between alcohol consumption and cortisol levels has not been evaluated. METHODS: This study examined 8,922 participants from the Dong-gu Study. The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as an instrumental variable for alcohol consumption. The association between the genetically predicted alcohol consumption and cortisol level was evaluated with Mendelian randomization (MR) using two-stage least squares regression. RESULTS: Alcohol consumption was positively associated with the serum cortisol level in both sexes in the observational analysis. In the MR analysis, the genetically predicted alcohol consumption was positively related to the cortisol level in men, with cortisol levels increasing by 0.18 µg/dL per drink per day. However, there was no relationship in women in the MR analysis. CONCLUSION: The predicted alcohol consumption according to the ALDH2 rs671 polymorphism was positively related to the cortisol levels, suggesting a causal relationship between alcohol consumption and cortisol levels.

5.
Antioxidants (Basel) ; 10(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34356372

RESUMO

4-Oxo-nonenal (4-ONE) is an endogenous lipid peroxidation product that is more reactive than 4-hydroxy-nonenal (4-HNE). We previously reported the arrhythmic potential of 4-HNE by suppression of cardiac human Ether-a-go-go Related Gene (hERG) K+ channels with prolonged action potential duration (APD) in cardiomyocytes. Here, we illustrate the higher arrhythmic risk of 4-ONE by modulating the cardiac hNaV1.5 channel currents (INaV). Although the peak amplitude of INaV was not significantly changed by 4-ONE up to 10 µM, the rate of INaV inactivation was slowed, and the late Na+ current (INaL) became larger by 10 µM 4-ONE. The chemical modification of specific residues in hNaV1.5 by 4-ONE was identified using MS-fingerprinting analysis. In addition to the changes in INaV, 4-ONE decreased the delayed rectifier K+ channel currents including the hERG current. The L-type Ca2+ channel current was decreased, whereas its inactivation was slowed by 4-ONE. The APD prolongation by 10 µM of 4-ONE was more prominent than that by 100 µM of 4-HNE. In the computational in silico cardiomyocyte simulation analysis, the changes of INaL by 4-ONE significantly exacerbated the risk of arrhythmia exhibited by the TdP marker, qNet. Our study suggests an arrhythmogenic effect of 4-ONE on cardiac ion channels, especially hNaV1.5.

6.
J Infect Public Health ; 14(9): 1151-1154, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34364306

RESUMO

The first surge of coronavirus disease 2019 (COVID-19) cases began on June 27, 2020 in Gwangju metropolitan city, located in the southwestern part of South Korea, with a population of 1,501,000. Local governments and the Korean Center for Disease Control and Prevention immediately started an epidemiologic investigation and traced the contacts of patients using a wide variety of data sources, including location data from mobile devices, credit card transaction, and closed-circuit television footage. Until July 16, 2020, 138 community transmission cases and 10 infection clusters were identified across the city. Through contact tracing, epidemiologic relatedness was found in 136 (98.6%) of 138 cases. Our investigation showed how the extensive and meticulous contact tracing suppressed COVID-19 outbreak in a populated city.


Assuntos
COVID-19 , Busca de Comunicante , Surtos de Doenças/prevenção & controle , Humanos , República da Coreia/epidemiologia , SARS-CoV-2
7.
Yonsei Med J ; 62(9): 792-798, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34427064

RESUMO

PURPOSE: In this prospective study, we evaluated the association between the serum levels of antioxidants uric acid (UA), albumin, and total bilirubin and the risk of cancer in a Korean population. MATERIALS AND METHODS: A total of 15882 subjects were followed up for cancer development and cancer-related death. During the follow-up period, 1619 cancer diagnoses and 617 cancer-related deaths were recorded. Cox proportional regression was performed to calculate the hazard ratio (HR) per standard deviation (SD) increment and 95% confidence interval (CI). The model was adjusted for covariates such as the age, sex, smoking, alcohol consumption, physical activity, education level, body mass index, and family history. Sensitivity analyses using the study subjects with physiological serum levels of each indicator were also performed. RESULTS: UA levels were positively correlated with cancer risk (HR per SD increment 1.04; 95% CI, 1.01-1.09), and albumin levels were inversely associated with the overall cancer risk (HR, 0.92; 95% CI, 0.88-0.96) and cancer-related death (HR, 0.86; 95% CI, 0.80-0.93). Total bilirubin levels were negatively correlated with the risk of cancer-related death (HR, 0.91; 95% CI, 0.83-0.99). By cancer type, UA was positively associated with prostate cancer, total bilirubin was positively associated with liver cancer, and albumin was inversely associated with lung cancer. CONCLUSION: The findings of this study support the role of antioxidants in carcinogenesis. Future large-cohort studies are needed to confirm the predictive value of albumin, UA, and total bilirubin levels in each type of cancer.


Assuntos
Neoplasias , Ácido Úrico , Bilirrubina , Humanos , Masculino , Neoplasias/epidemiologia , Estudos Prospectivos , República da Coreia/epidemiologia , Albumina Sérica
8.
Clin Exp Pediatr ; 64(11): 552-558, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34015896

RESUMO

The food shortage in North Korea is a serious situation that has spanned the mid-1990s to today. North Korean refugee children, even those born in North Korea, China, or South Korea, had poor nutritional status at birth; thus, their growth and nutritional status should be continuously monitored. This review focused on the health status of North Korean children and the nutritional status of North Korean refugee children upon settling in South Korea. Immediately after entering South Korea, North Korean refugee children were shorter and lighter than South Korean children and had a serious nutritional status. Over time, their nutrition status improved, but they remained shorter and lighter than South Korean children. A new obesity problem was also observed. Therefore, it is necessary to continuously monitor their growth and nutritional status.

9.
Pflugers Arch ; 473(4): 659-671, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33586023

RESUMO

Innate-like CD5+ B1a cells localized in serous cavities are activated by innate stimuli, such as lipopolysaccharide (LPS), leading to T cell-independent antibody responses. Although ion channels play crucial roles in the homeostasis and activation of immune cells, the electrophysiological properties of B1a cells have not been investigated to date. Previously, in the mouse B cell lymphoma cells, we found that the voltage-independent two-pore-domain potassium (K2P) channels generate a negative membrane potential and drive Ca2+ influx. Here, we newly compared the expression and activities of K2P channels in mouse splenic follicular B (FoB), marginal zone B (MZB), and peritoneal B1a cells. Next-generation sequencing analysis showed higher levels of transcripts for TREK-2 and TWIK-2 in B1a cells than those in FoB or MZB cells. Electrophysiological analysis, using patch clamp technique, revealed higher activity of TREK-2 with the characteristic large unitary conductance (~ 250 pS) in B1a than that in FoB or MZB cells. TREK-2 activity was further increased by LPS treatment (>2 h), which was more prominent in B1a than that in MZB or FoB cells. The cytosolic Ca2+ concentration of B cells was decreased by high-K+-induced depolarization (ΔRKCl (%)), suggesting the basal Ca2+ influx to be driven by negative membrane potential. The LPS treatment significantly increased the ΔRKCl (%) in B1a, though not in FoB and MZB cells. Our study was the first to compare the K2P channels in mouse primary B cell subsets, elucidating the functional upregulation of TREK-2 and augmentation of Ca2+ influx by the stimulation of Toll-like receptor 4 in B1a cells.

10.
Maturitas ; 143: 178-183, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33308626

RESUMO

OBJECTIVE: To assess the associations among the estimated glomerular filtration rate (eGFR), albumin to creatinine ratio (ACR), and all-cause and CVD mortality rate and to compare the performances of eGFRMDRD, eGFRCKD-EPI, and eGFRcys using receiver operating characteristic (ROC) analysis in Korean adults aged ≥ 50 years. METHODS: Of the 9,260 subjects who participated in the baseline survey of a prospective longitudinal study conducted in Korea, 9,009 (men: 3,574 (39.7%); women: 5,435 (60.3%)) were included in this analysis after the exclusion of 217 subjects with missing eGFR and 34 subjects with missing ACR data. MAIN OUTCOME MEASURE: The associations of eGFR and ACR with all-cause and CVD mortality were investigated using Cox proportional hazards models that included sex, age, waist circumference, smoking, alcohol intake, degree of physical activity, hypertension, diabetes, systolic blood pressure, log-HbA1c, total cholesterol, log-triglyceride, log-HDL and log-ACR or eGFR. RESULTS: After adjustment for covariates, independent associations were found between all-cause mortality and the eGFRcys (mL/min per 1.73 m2) [HR 1.23, 95% confidence interval (CI) 1.05-1.43 for 60-89 vs. ≥ 90; HR 1.87, 95% CI 1.49-2.34 for 45-59 vs. ≥ 90; HR 2.38, 95% CI 1.77-3.20 for 30-44 vs. ≥ 90; HR 2.82, 95% CI 1.89-4.23 for <30 vs. ≥ 90] and ACR (µg/mg creatinine) [HR 1.09, 95% CI 0.88-1.34 for Q2 vs. Q1; HR 1.34, 95% CI 1.10-1.63 for Q3 vs. Q1; HR 1.49, 95% CI 1.22-1.81 for Q4 vs. Q1]. In addition, independent associations of CVD mortality with the eGFRcys and ACR were significant. In the comparison of eGFR performance, the ROC-plot AUC for all-cause mortality was significantly greater for the eGFRcys than for the eGFRMDRD and eGFRCKD-EPI. CONCLUSION: The eGFRcys and ACR were associated independently with all-cause and CVD mortality after adjustment for covariates, including the eGFRcys and ACR. In addition, the ROC-plot AUC for all-cause mortality was greater for the eGFRcys than for the eGFRMDRD and eGFRCKD-EPI in Korean adults aged ≥ 50 years.


Assuntos
Albuminúria/mortalidade , Doenças Cardiovasculares/mortalidade , Taxa de Filtração Glomerular , Idoso , Idoso de 80 Anos ou mais , Albuminúria/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Cistatina C , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia
11.
Biochem Biophys Res Commun ; 534: 590-596, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33199024

RESUMO

Calcium homeostasis modulator 1 (calhm1) proteins form an outwardly rectifying nonselective ion channel having exceedingly slow kinetics and low sensitivity to voltage that is shifted by lowering extracellular Ca2+ ([Ca2+]e). Here we found that physiological temperature dramatically facilitates the voltage-dependent activation of the calhm1 current (Icalhm1); increased amplitude (Q10, 7-15) and fastened speed of activation. Also, the leftward shift of the half-activation voltage (V1/2) was similary observed in the normal and lower [Ca2+]e. Since calhm1 is highly expressed in the brain and taste cells, the thermosensitivity should be considered in their electrophysiology.


Assuntos
Canais de Cálcio/metabolismo , Glicoproteínas de Membrana/metabolismo , Animais , Encéfalo/metabolismo , Cálcio/metabolismo , Canais de Cálcio/genética , Fenômenos Eletrofisiológicos , Células HEK293 , Humanos , Cinética , Glicoproteínas de Membrana/genética , Camundongos , Técnicas de Patch-Clamp , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Papilas Gustativas/metabolismo , Temperatura
12.
Int J Mol Sci ; 23(1)2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-35008778

RESUMO

Cardiac radioablation is emerging as an alternative option for refractory ventricular arrhythmias. However, the immediate acute effect of high-dose irradiation on human cardiomyocytes remains poorly known. We measured the electrical activities of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) upon irradiation with 0, 20, 25, 30, 40, and 50 Gy using a multi-electrode array, and cardiomyocyte function gene levels were evaluated. iPSC-CMs showed to recover their electrophysiological activities (total active electrode, spike amplitude and slope, and corrected field potential duration) within 3-6 h from the acute effects of high-dose irradiation. The beat rate immediately increased until 3 h after irradiation, but it steadily decreased afterward. Conduction velocity slowed in cells irradiated with ≥25 Gy until 6-12 h and recovered within 24 h; notably, 20 and 25 Gy-treated groups showed subsequent continuous increase. At day 7 post-irradiation, except for cTnT, cardiomyocyte function gene levels increased with increasing irradiation dose, but uniquely peaked at 25-30 Gy. Altogether, high-dose irradiation immediately and reversibly modifies the electrical conduction of cardiomyocytes. Thus, compensatory mechanisms at the cellular level may be activated after the high-dose irradiation acute effects, thereby, contributing to the immediate antiarrhythmic outcome of cardiac radioablation for refractory ventricular arrhythmias.

13.
PLoS One ; 15(11): e0241963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33156888

RESUMO

This study assessed the nutritional status of children and adolescents from North Korean refugee (NKR) families who have settled and are living in South Korea (SK). Among the 547 individuals who participated in the study, 526 were ultimately included after excluding 21 with missing height or weight data. Their nutritional status was estimated using the 2017 Korean National Growth Charts for children and adolescents. Stunting, underweight, wasting, and obesity were defined as a height-for-age z-score < -2.0, weight-for-age z-score < -2.0, weight-for-height z-score < -2.0, and body mass index z-score > 2.0, respectively. The overall prevalence of stunting, underweight, wasting, and obesity was 7.0%, 6.8%, 5.3%, and 9.1%, respectively. Meanwhile, the prevalence of stunting, underweight, wasting, and obesity was 5.4%, 7.0%, 7.6%, and 10.3% for individuals settled in SK for <5 years and 6.1%, 6.1%, 0.0%, and 13.3% for those living in SK for ≥5 years, respectively. Therefore, children and adolescents from NKR families experience the double burden of malnutrition and obesity.


Assuntos
Transtornos do Crescimento/epidemiologia , Obesidade Pediátrica/epidemiologia , Refugiados , Magreza/epidemiologia , Síndrome de Emaciação/epidemiologia , Adolescente , Estatura , Peso Corporal , Criança , Pré-Escolar , República Democrática Popular da Coreia , Feminino , Humanos , Masculino , Estado Nutricional , Prevalência , República da Coreia/epidemiologia , República da Coreia/etnologia
14.
Antiviral Res ; 184: 104955, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33091434

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is considered as the most significant global public health crisis of the century. Several drug candidates have been suggested as potential therapeutic options for COVID-19, including remdesivir, currently the only authorized drug for use under an Emergency Use Authorization. However, there is only limited information regarding the safety profiles of the proposed drugs, in particular drug-induced cardiotoxicity. Here, we evaluated the antiviral activity and cardiotoxicity of remdesivir using cardiomyocytes-derived from human pluripotent stem cells (hPSC-CMs) as an alternative source of human primary cardiomyocytes (CMs). In this study, remdesivir exhibited up to 60-fold higher antiviral activity in hPSC-CMs compared to Vero E6 cells; however, it also induced moderate cardiotoxicity in these cells. To gain further insight into the drug-induced arrhythmogenic risk, we assessed QT interval prolongation and automaticity of remdesivir-treated hPSC-CMs using a multielectrode array (MEA). As a result, the data indicated a potential risk of QT prolongation when remdesivir is used at concentrations higher than the estimated peak plasma concentration. Therefore, we conclude that close monitoring of the electrocardiographic/QT interval should be advised in SARS-CoV-2-infected patients under remdesivir medication, in particular individuals with pre-existing heart conditions.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , COVID-19/virologia , Miócitos Cardíacos/virologia , Células-Tronco Pluripotentes/citologia , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/farmacologia , Alanina/farmacologia , Amidas/farmacologia , Animais , Antimaláricos/farmacologia , COVID-19/complicações , COVID-19/tratamento farmacológico , Chlorocebus aethiops , Cloroquina/farmacologia , Eletrocardiografia , Citometria de Fluxo , Cardiopatias/complicações , Humanos , Hidroxicloroquina/farmacologia , Microscopia de Fluorescência , Miócitos Cardíacos/efeitos dos fármacos , Células-Tronco Pluripotentes/virologia , Pirazinas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Vero , Ensaio de Placa Viral
15.
PLoS One ; 15(5): e0232899, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392240

RESUMO

Various nanopatterning techniques have been developed to improve cell proliferation and differentiation efficiency. As we previously reported, nanopillars and pores are able to sustain human pluripotent stem cells and differentiate pancreatic cells. From this, the nanoscale patterns would be effective environment for the co-culturing of epithelial and mesenchymal cell types. Interestingly, the nanopatterning selectively reduced the proliferative rate of mesenchymal cells while increasing the expression of adhesion protein in epithelial type cells. Additionally, co-cultured cells on the nanopatterning were not negatively affected in terms of cell function metabolic ability or cell survival. This is in contrast to conventional co-culturing methods such as ultraviolet or chemical treatments. The nanopatterning appears to be an effective environment for mesenchymal co-cultures with typically low proliferative rates cells such as astrocytes, neurons, melanocytes, and fibroblasts without using potentially damaging treatments.


Assuntos
Técnicas de Cocultura/instrumentação , Células Epiteliais , Células-Tronco Mesenquimais , Nanoestruturas , Animais , Adesão Celular , Proliferação de Células , Sobrevivência Celular , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Fibroblastos/citologia , Fibroblastos/fisiologia , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Camundongos , Propriedades de Superfície
16.
BMB Rep ; 53(8): 437-441, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32336319

RESUMO

In accordance with requirements of the ICH S7B safety pharmacology guidelines, numerous next-generation cardiotoxicity studies using human stem cell-derived cardiomyocytes (CMs) are being conducted globally. Although several stem cell-derived CMs are being developed for commercialization, there is insufficient research to verify if these CMs can replace animal experiments. In this study, in vitro high-efficiency CMs derived from human embryonic stem cells (hESC-CMs) were compared with Sprague-Dawley rats as in vivo experimental animals, and primary cultured in vitro rat-CMs for cardiotoxicity tests. In vivo rats were administrated with two consecutive injections of 100 mg/kg isoproterenol, 15 mg/kg doxorubicin, or 100 mg/kg nifedipine, while in vitro rat-CMs and hESC-CMs were treated with 5 µM isoproterenol, 5 µM doxorubicin, and 50 µM nifedipine. We have verified the equivalence of hESC-CMs assessments over various molecular biological markers, morphological analysis. Also, we have identified the advantages of hESC-CMs, which can distinguish between species variability, over electrophysiological analysis of ion channels against cardiac damage. Our findings demonstrate the possibility and advantage of high-efficiency hESC-CMs as next-generation cardiotoxicity assessment. [BMB Reports 2020; 53(8): 437-441].


Assuntos
Cardiotoxicidade/metabolismo , Células-Tronco Embrionárias/metabolismo , Miócitos Cardíacos/fisiologia , Animais , Cardiotoxicidade/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Doxorrubicina/farmacologia , Doxorrubicina/toxicidade , Humanos , Células-Tronco Pluripotentes Induzidas , Isoproterenol/farmacologia , Isoproterenol/toxicidade , Masculino , Nifedipino/farmacologia , Nifedipino/toxicidade , Ratos , Ratos Sprague-Dawley
17.
Int J Stem Cells ; 13(2): 287-294, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32323512

RESUMO

Cell labeling technologies are required to monitor the fate of transplanted cells in vivo and to select target cells for the observation of certain changes in vitro. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been transplanted for the treatment of heart injuries or used in vitro for preclinical cardiac safety assessments. Cardiomyocyte (CM) labeling has been used in these processes to facilitate target cell monitoring. However, the functional effect of the labeling agent on hiPSC-CMs has not been studied. Therefore, we investigated the effects of labeling agents on CM cellular functions. 3'-Dioctadecyloxacarbocyanine perchlorate (DiO), quantum dots (QDs), and a DNA plasmid expressing EGFP using Lipo2K were used to label hiPSC-CMs. We conclude that the hiPSC-CM labeling with DiO and QDs does not induce arrhythmogenic effects but rather improves the mRNA expression of cardiac ion channels and Ca2+ influx by L-type Ca2+ channels. Thus, DiO and QD labeling agents may be useful tools to monitor transplanted CMs, and further in vivo influences of the labeling agents should be investigated in the future.

18.
J Korean Med Sci ; 35(9): e14, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32141245

RESUMO

BACKGROUND: Elevated blood pressure is a major preventable cause of cardiovascular diseases. Alcohol consumption is a well-known risk factor of elevated blood pressure. The aldehyde dehydrogenase 2 (ALDH2) polymorphism is common in Eastern Asians, and inactive ALDH2 genotypes are associated with both avoiding alcohol consumption and aldehyde accumulation. Therefore, this study assessed the associations between alcohol consumption and hypertension and blood pressure according to the ALDH2 genotypes. METHODS: This study consists of 8,526 participants in the Dong-gu Study. Multivariate logistic regression was used to calculate the odds ratio (OR) according to alcohol consumption after stratifying by gender and ALDH2 genotypes. Multivariate linear regression was performed to estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP) according to the amount of alcohol consumed. RESULTS: In men, alcohol consumption was positively associated with both SBP and DBP in active ALDH2 carriers, but not in inactive ALDH2 carriers. In active ALDH2 carriers, compared to non-drinkers, the OR of hypertension was 1.16 (95% confidence interval [CI], 0.91-1.49) for < 1 drink/day, and 1.44 (95% CI, 1.15-1.80) for ≥ 1 drink/day in men. With each 1 drink/day increase, SBP and DBP increased by 3 and 1 mmHg in men, respectively. There was no significant association between ALDH2 genotypes and hypertension and blood pressure in women. CONCLUSION: ALDH2 genotype modified the association between alcohol consumption and blood pressure in men. There was a positive relationship between alcohol consumption and blood pressure in active ALDH2 carriers, but no significant relationship in inactive ALDH2 carriers.


Assuntos
Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial/genética , Pressão Sanguínea/fisiologia , Hipertensão/diagnóstico , Alelos , Feminino , Frequência do Gene , Genótipo , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético , República da Coreia/epidemiologia , Fatores de Risco
19.
Maturitas ; 133: 54-59, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32005424

RESUMO

OBJECTIVES: To assess the association between low muscle mass and osteoporosis in the Korean general population. METHODS: We analyzed 14,429 participants (6,261 men and 8,168 women) from the 2009-2011 Korean National Health and Nutrition Examination Survey (KNHANES) aged 20 years or more. MAIN OUTCOME MEASURE: The association of low muscle mass with osteoporosis was investigated using multivariate logistic regression models that included age, marital status, residence, current smoking, monthly drinking, physical activities, strength exercise, comorbidity, and the use of dietary supplements, and in women postmenopausal status and experience of pregnancy. RESULTS: After adjusting for covariates, low muscle mass was significantly associated with osteoporosis in the lumbar spine and femoral neck in both men (lumbar spine: OR 1.73, 95 % CI 1.08-2.76; femoral neck: OR 3.39, 95 % CI 1.69-6.80) and women (lumbar spine: OR 1.52, 95 % CI 1.17-1.97; femoral neck: OR 2.09, 95 % CI 1.56-2.80). Also, the association between low muscle mass and osteoporosis was significant in men and women in every age group except for men aged 50-64 years. CONCLUSION: Low muscle mass was significantly associated with osteoporosis in both men and women for all age groups, except for men aged 50-64 years.


Assuntos
Músculo Esquelético/patologia , Atrofia Muscular/epidemiologia , Osteoporose/epidemiologia , Adulto , Idoso , Feminino , Colo do Fêmur , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , República da Coreia/epidemiologia
20.
Clin Exp Pharmacol Physiol ; 47(1): 38-48, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31444788

RESUMO

Endothelium-dependent vasorelaxation is partly mediated by small-conductance (SK3) and intermediate-conductance Ca2+ -activated K+ channels (SK4) in the endothelium that results in endothelium-dependent hyperpolarization (EDH). Apart from the electrical propagation through myoendothelial gap junctions, the K+ released from the endothelium facilitates EDH by increasing inward rectifier K+ channel (Kir) conductance in smooth muscle cells. The EDH-dependent relaxation of coronary artery (CA) and Kir current in smooth muscle cells (CASMCs) of hypertensive animals are poorly understood despite the critical role of coronary flow in the hypertrophic heart. In spontaneously hypertensive (SHR) and control (WKY) rats, we found attenuation of the CA relaxation by activators of SK3 and SK4 (NS309 and 1-EBIO) in SHR. In isolated CASMCs, whole-cell patch-clamp study revealed larger IKir in SHR than WKY, whereas the myocytes of skeletal and cerebral arteries showed smaller IKir in SHR than WKY. While the treatment with IKir inhibitor (0.1 mmol/L Ba2+ ) alone did not affect the WKY-CA, the SHR-CA showed significant contractile response, suggesting relaxing influence of the higher IK ir in the CASMCs of SHR. Furthermore, the attenuation of NS309-induced relaxation of CA by the combined treatment with 0.1 mmol/L Ba2+ was more prominent in SHR than WKY. Our study firstly shows a distinct increase of IK ir in the CASMCs of SHR, which could partly compensate for the attenuated relaxation via endothelial SK3 and SK4.


Assuntos
Vasos Coronários/metabolismo , Endotélio Vascular/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Canais de Potássio Cálcio-Ativados/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Vasodilatação/fisiologia , Acetilcolina/metabolismo , Animais , Hipertensão/metabolismo , Potenciais da Membrana/fisiologia , Artérias Mesentéricas/metabolismo , Contração Muscular/fisiologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
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