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Objectives: This study investigated the associations between several obesity-related anthropometric indices and mortality in middle-aged and elderly populations to compare the indices' predictive ability with that of the body mass index (BMI). Methods: We analyzed data on 12 indices calculated from 19,805 community-based cohort participants (average age, 63.27 years; median follow-up, 13.49 years). Each index was calculated using directly measured values of height, weight, waist circumference (WC), and hip circumference (HC). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for each index using Cox regression and evaluated mortality prediction with the Harrell c-index. Results: Adding anthropometric indices to the basic mortality model (c-index 0.7723; 95% CI, 0.7647-0.7799) significantly increased the predictive power of BMI (c-index 0.7735; 95% CI, 0.7659-0.7811), a body shape index (ABSI, c-index 0.7735; 95% CI, 0.7659-0.7810), weight-adjusted waist index (WWI, c-index 0.7731; 95% CI, 0.7656-0.7807), and waist to hip index (WHI, c-index 0.7733; 95% CI, 0.7657-0.7809). The differences between the BMI model and the other 3 models were not statistically significant. Conclusion: In predicting all-cause mortality, the ABSI, WWI, and WHI models based on WC or HC had stronger predictive power than conventional risk factors but were not significantly different from the BMI model.
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We studied lysosomal Ca2+ in inflammasome. Lipopolysaccharide (LPS) + palmitic acid (PA) decreased lysosomal Ca2+ ([Ca2+]Lys) and increased [Ca2+]i through mitochondrial ROS, which was suppressed in Trpm2-KO macrophages. Inflammasome activation and metabolic inflammation in adipose tissue of high-fat diet (HFD)-fed mice were ameliorated by Trpm2 KO. ERâlysosome Ca2+ refilling occurred after lysosomal Ca2+ release whose blockade attenuated LPS + PA-induced inflammasome. Subsequently, store-operated Ca2+entry (SOCE) was activated whose inhibition suppressed inflammasome. SOCE was coupled with K+ efflux whose inhibition reduced ER Ca2+ content ([Ca2+]ER) and impaired [Ca2+]Lys recovery. LPS + PA activated KCa3.1 channel, a Ca2+-activated K+ channel. Inhibitors of KCa3.1 channel or Kcnn4 KO reduced [Ca2+]ER, attenuated increase of [Ca2+]i or inflammasome activation by LPS + PA, and ameliorated HFD-induced inflammasome or metabolic inflammation. Lysosomal Ca2+ release induced delayed JNK and ASC phosphorylation through CAMKII-ASK1. These results suggest a novel role of lysosomal Ca2+ release sustained by ERâlysosome Ca2+ refilling and K+ efflux through KCa3.1 channel in inflammasome activation and metabolic inflammation.
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Calcio , Retículo Endoplásmico , Inflamasomas , Inflamación , Lisosomas , Ratones Noqueados , Potasio , Animales , Inflamasomas/metabolismo , Ratones , Lisosomas/metabolismo , Calcio/metabolismo , Potasio/metabolismo , Inflamación/metabolismo , Retículo Endoplásmico/metabolismo , Lipopolisacáridos , Canales Catiónicos TRPM/metabolismo , Canales Catiónicos TRPM/genética , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/metabolismo , Ratones Endogámicos C57BL , Macrófagos/metabolismo , Masculino , Dieta Alta en GrasaRESUMEN
OBJECTIVE: The daily lives of adolescents have changed significantly because of COVID-19 pandemic. We investigated the effects of changes in daily life attributed to COVID-19 on allergic diseases among Korean adolescents. METHODS: Data from the 2021 Korea Youth Risk Behavior Survey were used. In total, 54,848 survey participants were included in the analysis. Allergic diseases included allergic rhinitis, atopic dermatitis, and asthma. Changes attributed to COVID-19 included family economic difficulties, physical activity, breakfast skipping frequency, alcohol consumption, smoking, and depressive moods. Chi-square tests and multiple logistic regression analyses were conducted to examine the impact of changes in daily life attributed to COVID-19 on allergic diseases. RESULTS: Among the Korean adolescents surveyed, 29.8% experienced a deterioration in their economic status due to COVID-19, 49.1% reported decreased physical activity, 2.8% reported increased alcohol consumption, 1.0% reported an increase in their smoking behavior, and 36.9% reported an increase in depressive moods. Those diagnosed with atopic dermatitis, allergic rhinitis, or asthma within the previous 12 months accounted for 17.1%, 6.2%, and 1.0% of the population, respectively. Adolescents who were significantly affected by COVID-19 in their daily lives were frequently diagnosed with allergic diseases within the last 12 months. CONCLUSION: Changes in daily life due to COVID-19, including decreased physical activity and increased depressive mood, were common in adolescents and were associated with an increased prevalence of allergic diseases. Since changes in daily life due to the pandemic may increase the burden of allergic disease, additional interventions for disease management should be considered.
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Mutations within the SCN5A gene, which encodes the α-subunit 5 (NaV1.5) of the voltage-gated Na+ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the NaV1.5 current (INa) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of INa was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the coexpression of SCN1B with p.A385T/R504T revealed significant reduction of INa and slower recovery from inactivation, consistent with the loss-of-function in Na+ channels. The SCN1B dependent reduction of INa was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of NaV1.5, respectively.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) was first reported in December 2019 and the first case in Korea was confirmed on January 20, 2020. Due to the absence of therapeutic agents and vaccines, the Korean government implemented social distancing on February 29, 2020. This study aimed to examine the effect of physical activity (PA) on health through changes in multi-omics biomarkers with a 6-month of exercise intervention during the first wave of COVID-19 in Korea. METHODS: Twenty-seven healthy middle-aged women were recruited and 14 subjects completed the exercise intervention. The mean age (± SD) was 46.3 (± 5.33) and the mean BMI (± SD) was 24.9 (± 3.88). A total of three blood and stool samples were collected at enrollment, after period 1, and after period 2 (3-month intervals). The amount of PA was measured with an accelerometer and by questionnaire. Clinical variables were used, including blood pressure, grip strength, flexibility, and blood glucose levels and lipid markers obtained from laboratory tests. The concentration of blood metabolites was measured by targeted metabolomics. Fecal microbiome data were obtained by 16 S rRNA gene amplicon sequencing. RESULTS: During the second half period (period 2), Coronavirus disease 2019 occurred and spread out in Korea, and PA decreased compared with the first half period (period 1) (185.9 ± 168.73 min/week to 102.5 ± 82.30 min/week; p = 0.0101). Blood pressure, hemoglobin A1c (HbA1c), and low-density lipoprotein cholesterol (LDL-C) decreased in period 1 (p < 0.05) and tended to increase again during period 2 (p < 0.05). Forty metabolites were changed significantly during period 1 (FDR p < 0.05), and we found that 6 of them were correlated with changes in blood pressure, HbA1c, and LDL-C via network analysis. CONCLUSIONS: Our results may suggest that exercise improves health through changes in biomarkers at multi-omics levels. However, reduced PA due to COVID-19 can adversely affect health, emphasizing the necessity for sustained exercise and support for home-based fitness to maintain health. TRIAL REGISTRATION: The trial is retrospectively registered on ClinicalTrials.gov (NCT05927675; June 30, 2023).
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The c.453delC (p.Thr152Profs*14) frameshift mutation in KCNH2 is associated with an elevated risk of Long QT syndrome (LQTS) and fatal arrhythmia. Nevertheless, the loss-of-function mechanism underlying this mutation remains unexplored and necessitates an understanding of electrophysiology. To gain insight into the mechanism of the LQT phenotype, we conducted whole-cell patch-clamp and immunoblot assays, utilizing both a heterologous expression system and patient-derived induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) with 453delC-KCNH2. We also explored the site of translational reinitiation by employing LC/MS mass spectrometry. Contrary to the previous assumption of early termination of translation, the findings of this study indicate that the 453delC-KCNH2 leads to an N-terminally truncated hERG channel, a potential from a non-canonical start codon, with diminished expression and reduced current (IhERG). The co-expression with wildtype KCNH2 produced heteromeric hERG channel with mild dominant-negative effect. Additionally, the heterozygote patient-derived iPSC-CMs exhibited prolonged action potential duration and reduced IhERG, which was ameliorated with the use of a hERG activator, PD-118057. The results of our study offer novel insights into the mechanisms involved in congenital LQTS associated with the 453delC mutation of KCNH2. The mutant results in the formation of less functional N-terminal-truncated channels with reduced amount of membrane expression. A hERG activator is capable of correcting abnormalities in both the heterologous expression system and patient-derived iPSC-CMs.
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Células Madre Pluripotentes Inducidas , Síndrome de QT Prolongado , Humanos , Miocitos Cardíacos/metabolismo , Mutación del Sistema de Lectura , Células Madre Pluripotentes Inducidas/metabolismo , Canales de Potasio Éter-A-Go-Go/genética , Canal de Potasio ERG1/genética , Canal de Potasio ERG1/metabolismo , Heterocigoto , Mutación , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/metabolismoRESUMEN
Agrimonia pilosa Ledeb., an important medicinal herb in traditional East Asian medicine, is primarily used to treat abdominal pain, dysentery, and hemostasis. There are ten other reported species of Agrimonia plants, including Agrimonia coreana Nakai-a naturally growing species in South Korea-and Agrimonia eupatoria Linn. Although recent studies have isolated numerous active constituents and investigated their effects, the medicinal utility of this herb is not yet fully explored. Through patch-clamp recording, a previous study reported that Agrimonia plant extracts inhibit the function of Ca2+ release-activated Ca2+ channels (CRACs). Herein, we aimed to identify and isolate the main compounds in A. coreana responsible for CRAC inhibition while assessing the anti-inflammatory effects mediated by this inhibition. We demonstrated for the first time that alphitolic acid isolated from A. coreana has a dose-dependent inhibitory effect on CRAC activity and, thus, an inhibitory effect on intracellular calcium increase. Furthermore, analysis of human CD4+ T cell proliferation via the carboxyfluorescein diacetate succinimidyl ester method revealed that alphitolic acid inhibited T cell proliferation in a concentration-dependent manner. Our findings provide a theoretical basis for the potential therapeutic use of alphitolic acid in the treatment of inflammatory diseases.
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Agrimonia , Humanos , Linfocitos T , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Antiinflamatorios/farmacologíaRESUMEN
BACKGROUND: Tuberculosis is an infectious disease influenced by social factors rather than a simple infectious disease. In this study, we investigated the relationship between tuberculosis rates and socioeconomic status. METHODS: This study was conducted using data of the 49,483 participants of the Korean National Health and Nutrition Examination Survey (KNHANES) VI-VIII (2013-2021). The relationships between tuberculosis rates and the quartiles of monthly household income and education level were examined using a multivariate logistic regression analysis. RESULTS: The KNHANES data revealed that the prevalence of tuberculosis as substantially related to monthly household income (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.1-32.0 for lowest vs. highest incomes) and education level (OR, 3.8; 95% CI, 1.2-12.0 for 10-12 years vs. ≥13 years; OR, 4.1; 95% CI, 1.2-14.8 for ≤ 6 years vs. ≥13 years). Furthermore, current tuberculosis treatment was significantly related to monthly household income and education level. CONCLUSION: There were substantial correlations between tuberculosis rates and socioeconomic status in South Korea.
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Enfermedades Transmisibles , Tuberculosis , Humanos , Encuestas Nutricionales , Clase Social , Renta , República de Corea/epidemiología , Prevalencia , Tuberculosis/epidemiologíaRESUMEN
Acute upper gastrointestinal bleeding (UGIB) is one of the most urgent medical conditions, with peptic ulcer bleeding (PUB) accounting for most gastrointestinal bleeding cases. The Japanese scoring system was developed to predict the probability of intervention in patients with UGIB, and it is more effective than other scoring systems, according to several studies. This study aimed to verify whether the Japanese scoring system is better than other scoring systems in predicting the probability of intervention when limited to PUB in patients with UGIB. We enrolled patients who presented with symptoms of UGIB and were diagnosed with peptic ulcers using endoscopy. The performances of the scoring systems in predicting patient outcomes were validated and compared using the receiver-operating characteristic curve analysis. Additionally, we used the chi-square test, Fisher exact test, and the t test to analyze the association between the patients characteristics and clinical outcomes. Of the 1228 patients diagnosed with peptic ulcers, 90.6% underwent endoscopy. rebleeding occurred in 12.5% of the patients, and 2.5% of the patients died within 30 days. The Japanese score was the most effective in predicting the need for endoscopic intervention for PUB. Sex, systolic blood pressure, hematemesis, syncope, blood urea nitrogen level, and the American Society of Anesthesiologists score were predictive factors for the probability of endoscopic intervention in patients with PUB. The Japanese score is an effective predictor of the probability of endoscopic intervention in patients with PUB.
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Úlcera Péptica Hemorrágica , Úlcera Péptica , Humanos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Úlcera Péptica/complicaciones , Úlcera Péptica/diagnóstico , Úlcera Péptica Hemorrágica/diagnóstico , Úlcera Péptica Hemorrágica/terapia , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVES: In previous studies, high homocysteine levels were associated with high cardiovascular mortality. However, these results were inconsistent with those of randomized controlled trials. We aimed to evaluate the causal role of homocysteine on all-cause and cardiovascular mortality using Mendelian randomization (MR) analysis. METHODS: This study included the 10,005 participants in the Namwon Study. In conventional observational analysis, age, sex, survey years, lifestyles, body mass index, comorbidities, and serum folate level were adjusted using multivariate Cox proportional regression. MR using 2-stage least squares regression was used to evaluate the association between genetically predicted plasma homocysteine levels and mortality. Age, sex, and survey years were adjusted for each stage. The methylenetetrahydrofolate reductase (MTHFR) polymorphism was used as an instrumental variable for predicting plasma homocysteine levels. RESULTS: Observed homocysteine levels were positively associated with all-cause (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.26-1.54) and cardiovascular (HR, 1.62; 95% CI, 1.28-2.06) mortality when plasma homocysteine levels doubled. However, these associations were not significant in MR analysis. The HRs of doubling genetically predicted plasma homocysteine levels for all-cause and cardiovascular mortality were 0.99 (95% CI, 0.62-1.57) and 1.76 (95% CI, 0.54-5.77), respectively. CONCLUSIONS: This MR analysis did not support a causal role for elevated plasma homocysteine concentrations in premature deaths.
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PURPOSE: The outcomes of colorectal endoscopic submucosal dissection (ESD) in 15-19-mm tumors are unclear. This study compared the effectiveness and safety of colorectal ESD for 15-19-mm tumors and tumors exceeding that size. METHODS: From August 2018 to December 2020, 213 cases of colorectal tumors removed by colorectal ESD at a tertiary hospital were enrolled in this study. The cases were divided into two groups according to the pathologically measured size of the resected lesion: an intermediate group (15-19 mm, n = 62) and a large group (≥ 20 mm, n = 151). The en bloc resection rate, complete resection rate, and complications were investigated retrospectively. RESULTS: The en bloc resection rate was significantly higher in the intermediate than large group (100% vs. 94%, p = 0.049), and the mean total procedure time was shorter in the intermediate than large group (29.2 [Formula: see text] 12.6 vs. 48.4 [Formula: see text] 28.8 min, p < 0.001). However, the mean procedure speed was significantly lower in the intermediate than large group (0.25 [Formula: see text] 0.10 vs. 0.28 [Formula: see text] 0.11 cm2/min, p = 0.031). The complete resection rate, post-procedural bleeding, and perforation rate were not significantly different between the two groups. In multivariate analyses, the total procedure time and mean procedure speed were significantly associated with lesion size. CONCLUSION: Colorectal ESD of 15-19-mm lesions is effective, and has a shorter procedure time and higher en bloc resection rate than the same procedure for larger lesions.
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Humanos , Colonoscopía/métodos , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Disección/métodos , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Mucosa Intestinal/cirugía , Mucosa Intestinal/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: The association between bilirubin and atrial fibrillation (AF) has been evaluated previously in observational studies but with contradictory results. This study evaluated the causal association between serum bilirubin level and AF using Mendelian randomization (MR) analysis. METHODS: This cross-sectional study includes 8,977 participants from the Dong-gu Study. In the observational analysis, multivariate logistic regression was performed to evaluate the association between bilirubin and prevalent AF. To evaluate the causal association between bilirubin and AF, MR analysis was conducted by using the UGT1A1 rs11891311 and rs4148323 polymorphisms as instrumental variables. RESULTS: Elevated serum bilirubin levels were associated with an increased risk for AF in observational analysis (total bilirubin: odds ratio [OR], 1.31; 95% confidence interval [95% CI], 1.15-1.48 per 1 standard deviation [SD]; direct bilirubin: OR, 1.31; 95% CI, 1.18-1.46 per 1 SD), whereas the genetically predicted serum bilirubin levels in MR analysis did not show this association (total bilirubin: OR, 1.02; 95% CI, 0.67-1.53 per 1 SD; direct bilirubin: OR, 1.03; 95% CI, 0.61-1.73 per 1 SD). CONCLUSIONS: Genetically predicted bilirubin levels were not associated with prevalent AF. Thus, the observational association between serum bilirubin levels and AF may be non-causal and affected by reverse causality or unmeasured confounding.
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OBJECTIVES: This study aimed to evaluate the potential interaction between kidney function and the non-linear association between serum calcium levels and cardiovascular disease (CVD) mortality. METHODS: This study included 8927 participants enrolled in the Dong-gu Study. Albumin-corrected calcium levels were used and categorized into 6 percentile categories: <2.5th, 2.5-25.0th, 25.0-50.0th, 50.0-75.0th, 75.0-97.5th, and >97.5th. Restricted cubic spline analysis was used to examine the non-linear association between calcium levels and CVD mortality. Cox proportional hazard regression was used to estimate hazard ratios (HRs) for CVD mortality according to serum calcium categories. All survival analyses were stratified by the estimated glomerular filtration rate. RESULTS: Over a follow-up period of 11.9±2.8 years, 1757 participants died, of whom 219 died from CVD. A U-shaped association between serum calcium and CVD mortality was found, and the association was more evident in the low kidney function group. Compared to the 25.0-50.0th percentile group for serum calcium levels, both low and high serum calcium tended to be associated with CVD mortality (<2.5th: HR, 6.23; 95% confidence interval [CI], 1.16 to 33.56; >97.5th: HR, 2.56; 95% CI, 0.76 to 8.66) in the low kidney function group. In the normal kidney function group, a similar association was found between serum calcium levels and CVD mortality (<2.5th: HR, 1.37; 95% CI, 0.58 to 3.27; >97.5th: HR, 1.65; 95% CI, 0.70 to 3.93). CONCLUSIONS: We found a non-linear association between serum calcium levels and CVD mortality, suggesting that calcium dyshomeostasis may contribute to CVD mortality, and kidney function may modify the association.
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Calcio , Enfermedades Cardiovasculares , Humanos , Adulto , Factores de Riesgo , Riñón , República de Corea/epidemiologíaRESUMEN
This study aimed to investigate the coronavirus disease 2019 (COVID-19) infection prevention and control (IPC) practices and related factors among paramedics. We selected 249 paramedics using convenience sampling from three areas in Korea. Data on the demographics, infection-related characteristics, awareness, and practice of IPC were collected using self-reported questionnaires. The mean IPC practice score was 4.47 ± 0.54. The compliance with IPC practices was relatively high among those with a disease history (B = 0.194, p = 0.045) and who were aware of the safety management standard guidelines. Provision of sufficient protective equipment and infection prevention monitoring were associated with higher IPC practice scores. Education for increasing awareness of the recent IPC guidelines and the allocation of personal protective equipment would be helpful in improving the practice.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Paramédico , Equipo de Protección Personal , Brotes de Enfermedades/prevención & control , República de Corea/epidemiologíaRESUMEN
Insulin and insulin-like growth factor 1 (IGF-1) signaling regulate cellular growth and glucose metabolism in the myocardium. However, their physiological role in the cells of the cardiac conduction system has never been explored. Therefore, we sought to determine the spatiotemporal function of insulin/IGF-1 receptors in the sinoatrial node (SAN). We generated cardiac conduction cell-specific inducible IGF-1 receptor (IGF-1R) knockout (KO) (CSIGF1RKO), insulin receptor (IR) KO (CSIRKO), and IR/IGF-1R double-KO (CSDIRKO) mice and evaluated their phenotypes. Telemetric electrocardiography revealed regular sinus rhythm in CSIGF1RKO mice, indicating that IGF-1R is dispensable for normal pacemaking. In contrast, CSIRKO and CSDIRKO mice exhibited profound sinus bradycardia. CSDIRKO mice showed typical sinus node dysfunction characterized by junctional rhythm and sinus pauses on electrocardiography. Interestingly, the lack of an insulin receptor in the SAN cells of CSIRKO and CSDIRKO mice caused sinus nodal fibrosis. Mechanistically, hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) protein expression significantly decreased in the CSIRKO and CSDIRKO mice relative to the controls. A patch-clamp study of the SAN cells of CSIRKO mice revealed a significant decrease in the funny current, which is responsible for spontaneous diastolic depolarization in the SAN. This result suggested that insulin receptor loss reduces the heart rate via downregulation of the HCN4 channel. Additionally, HCN1 expression was decreased in CSDIRKO mice, explaining their sinus node dysfunction. Our results reveal a previously unrecognized role of insulin/IGF-1 signaling in sinus node structural maintenance and pacemaker function.
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Síndrome del Seno Enfermo , Nodo Sinoatrial , Ratones , Animales , Nodo Sinoatrial/metabolismo , Síndrome del Seno Enfermo/metabolismo , Receptor de Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Insulina/metabolismoRESUMEN
BACKGROUND: α-Mangostin is a xanthone isolated from the pericarps of mangosteen fruit with, and has analgesic properties. Although the effects suggest an interaction of α-mangostin with ion channels in the nociceptive neurons, electrophysiological investigation of the underlying mechanism has not been performed. HYPOTHESIS: We hypothesized that α-Mangostin exerts its analgesic effects by modulating the activity of various ion channels in dorsal root ganglion (DRG) neurons. METHODS: We performed a whole-cell patch clamp study using mouse DRG neurons, HEK293T cells overexpressing targeted ion channels, and ND7/23 cells. Molecular docking (MD) and in silico absorption, distribution, metabolism, and excretion (ADME) analyses were conducted to obtain further insights into the binding sites and pharmacokinetics, respectively. RESULTS: Application of α-mangostin (1-3 µM) hyperpolarized the resting membrane potential (RMP) of small-sized DRG neurons by increasing background K+ conductance and thereby inhibited action potential generation. At micromolar levels, α-mangostin activates TREK-1, TREK-2, or TRAAK, members of the two-pore domain K+ channel (K2P) family known to be involved in RMP formation in DRG neurons. Furthermore, capsaicin-induced TRPV1 currents were potently inhibited by α-mangostin (0.43 ± 0.27 µM), and partly suppressed tetrodotoxin-sensitive voltage-gated Na+ channel (NaV) currents. MD simulation revealed that multiple oxygen atoms in α-mangostin may form stable hydrogen bonds with TREKs, TRAAK, TRPV1, and NaV channels. In silico ADME tests suggested that α-mangostin may satisfy the drug-likeness properties without penetrating the blood-brain barrier. CONCLUSION: The analgesic properties of α-mangostin might be mediated by the multi-target modulation of ion channels, including TREK/TRAAK activation, TRPV1 inhibition, and reduction of the tetrodotoxin-sensitive NaV current. The findings suggest that the phytochemical can be a multi-ion channel-targeting drug and an alternative drug for effective pain management.
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Ganglios Espinales , Neuronas , Ratones , Humanos , Animales , Tetrodotoxina/metabolismo , Tetrodotoxina/farmacología , Células HEK293 , Simulación del Acoplamiento MolecularRESUMEN
The implantable cardioverter-defibrillator (ICD) is an effective method to prevent sudden cardiac death in high-risk patients. However, the transvenous lead is incompatible with large-area electrophysiological mapping and cannot accommodate selective multichannel precision stimulations. Moreover, it involves high-energy shocks, resulting in pain, myocardial damage, and recurrences of ventricular tachyarrhythmia (VTA). We present a method for VTA treatment based on subthreshold electrical stimulations using a stretchable epicardial multichannel electrode array, which does not disturb the normal contraction or electrical propagation of the ventricle. In rabbit models with myocardial infarction, the infarction was detected by mapping intracardiac electrograms with the stretchable epicardial multichannel electrode array. Then, VTAs could be terminated by sequential electrical stimuli from the epicardial multichannel electrode array beginning with low-energy subthreshold stimulations. Last, we used these subthreshold stimulations to prevent the occurrence of additional VTAs. The proposed protocol using the stretchable epicardial multichannel electrode array provides opportunities toward the development of innovative methods for painless ICD therapy.
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Desfibriladores Implantables , Infarto del Miocardio , Taquicardia Ventricular , Conejos , Animales , Taquicardia Ventricular/terapia , Taquicardia Ventricular/epidemiología , Taquicardia Ventricular/etiología , Desfibriladores Implantables/efectos adversos , Ventrículos Cardíacos , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Muerte Súbita Cardíaca/epidemiología , Infarto del Miocardio/terapia , Infarto del Miocardio/etiologíaRESUMEN
A reduced estimated glomerular filtration rate (eGFR) is a predictor for mortality in patients with acute myocardial infarction (AMI). This study aimed to compare mortality according to the GFR and eGFR calculation methods during long-term clinical follow-ups. Using the Korean Acute Myocardial Infarction Registry-National Institutes of Health Data, 13,021 patients with AMI were included in this study. Patients were divided into the surviving (n=11,503, 88.3%) and deceased (n=1,518, 11.7%) groups. Clinical characteristics, cardiovascular risk factors, and 3-year mortality-related factors were analyzed. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations. The surviving group was younger than the deceased group (62.6±12.4 vs. 73.6±10.5 years, p<0.001), whereas the deceased group had higher hypertension and diabetes prevalences than the surviving group. A high Killip class was more frequently observed in the deceased group. eGFR was significantly lower in the deceased group (82.2±24.1 vs. 55.2±28.6 ml/min/1.73 m2, p<0.001). Multivariate analysis revealed that low eGFR was an independent risk factor for mortality during the 3-year follow-up. The CKD-EPI equation was more useful for predicting mortality than the MDRD equation (0.766; 95% confidence interval [CI], 0.753-0.779 vs. 0.738; 95% CI, 0.724-0.753; p=0.001). Decreased renal function was a significant predictor of mortality after 3 years in patients with AMI. The CKD-EPI equation was more useful for predicting mortality than the MDRD equation.
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AIM: To assess the growth status of North Korean refugee adolescents (NKRA) living in South Korea (SK) and compare their growth status with that of SK adolescents (SKA). SUBJECTS AND METHODS: NKRA were interviewed from 2017 to 2020, whereas the data for SKA were from the 2016 to 2018 Korea National Health and Nutrition Examination Surveys. SKA and NKRA were matched by age and gender in a 3:1 ratio and 534 SKA and 185 NKRA were enrolled. RESULTS: After adjusting for the covariates, NKRA had greater prevalences of thinness (odds ratio [OR], 11.5; 95% confidence interval [CI], 2.9-45.6) and obesity (OR, 12.0; 95% CI, 3.1-46.1) than SKA, but were not of short stature. In comparison with SKA in low-income families, NKRA had similarly greater prevalences of thinness and obesity, but not of short stature. As the length of stay of NKRA in SK increased, the prevalence of short stature and thinness did not decrease, while the prevalence of obesity increased significantly. CONCLUSION: Although they had lived in SK for several years, NKRA had greater prevalences of thinness and obesity than SKA and the prevalence of obesity increased significantly with the length of stay in SK.