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Probiotic supplementation has sex-dependent effects on immune responses in association with the gut microbiota in community-dwelling older adults: a randomized, double-blind, placebo-controlled, multicenter trial.
Kim, CS, Jung, MH, Choi, EY, Shin, DM
Nutrition research and practice. 2023;(5):883-898
Abstract
BACKGROUND/OBJECTIVES Probiotics have been suggested as potent modulators of age-related disorders in immunological functions, yet little is known about sex-dependent effects of probiotic supplements. Therefore, we aimed to investigate sex-dependent effects of probiotics on profiles of the gut microbiota and peripheral immune cells in healthy older adults. SUBJECTS/METHODS In a randomized, double-blind, placebo-controlled, multicenter trial, healthy elderly individuals ≥ 65 yrs old were administered probiotic capsules (or placebo) for 12 wk. Gut microbiota was analyzed using 16S rRNA gene sequencing and bioinformatic analyses. Peripheral immune cells were profiled using flow cytometry for lymphocytes (natural killer, B, CD4+ T, and CD8+ T cells), dendritic cells, monocytes, and their subpopulations. RESULTS Compared with placebo, phylum Firmicutes was significantly reduced in the probiotic group in women, but not in men. At the genus level, sex-specific responses included reductions in the relative abundances of pro-inflammatory gut microbes, including Catabacter and unclassified_Coriobacteriales, and Burkholderia and unclassified Enterobacteriaceae, in men and women, respectively. Peripheral immune cell profiling analysis revealed that in men, probiotics significantly reduced the proportions of dendritic cells and CD14+ CD16- monocytes; however, these effects were not observed in women. In contrast, the proportion of total CD4+ T cells was significantly reduced in women in the probiotic group. Additionally, serum lipopolysaccharide-binding protein levels showed a decreasing tendency that were positively associated with changes in gut bacteria, including Catabacter (ρ = 0.678, P < 0.05) and Burkholderia (ρ = 0.673, P < 0.05) in men and women, respectively. CONCLUSIONS These results suggest that probiotic supplementation may reduce the incidence of inflammation-related diseases by regulating the profiles of the gut microbiota and peripheral immune cells in healthy elders in a sex-specific manner.
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Rivaroxaban Once-Daily vs. Dose-Adjusted Vitamin K Antagonist on Biomarkers in Acute Decompensated Heart Failure and Atrial Fibrillation (ROAD HF-AF): Rationale and Design of an Investigator-Initiated Multicenter Randomized Prospective Open-Labeled Pilot Clinical Study.
Cho, I, Oh, J, Kim, IC, Chung, H, Lee, JH, Kim, HM, Byun, YS, Yoo, BS, Choi, EY, Chung, WJ, et al
Frontiers in cardiovascular medicine. 2021;:765081
Abstract
Background: Clinical trials of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with chronic heart failure and atrial fibrillation (AF) have demonstrated reduced risks of stroke and bleeding compared with vitamin K antagonists (VKAs). Here, we aim to assess the clinical efficacy and safety of rivaroxaban, a NOAC, compared with warfarin, a VKA, and the effects of rivaroxaban on cardiovascular biomarkers in patients with acute decompensated heart failure (ADHF) with reduced ejection fraction (≤40%) and AF. Methods: Rivaroxaban Once-daily vs. dose-adjusted vitamin K antagonist on biomarkers in Acute Decompensated Heart Failure and Atrial Fibrillation (ROAD HF-AF) is a randomized, open-labeled, controlled, prospective, multicenter pilot study designed to assess cardiovascular biomarkers and the safety of rivaroxaban (20 or 15 mg in patients with creatinine clearance 30-49 mL/min per day) compared with VKA (target international normalized range: 2-3) in 150 patients hospitalized with ADHF and AF. The primary endpoint is the change in circulating high-sensitivity cardiac troponin (hsTn) during hospitalization. The secondary endpoints are bleeding, hospital stay duration, in-hospital mortality, and changes in cardiovascular, renal, and thrombosis biomarkers. Patients will be followed for 180 days. Conclusion: We hypothesize that rivaroxaban will reduce myocardial injury and hemodynamic stress, as reflected by the biomarker status, within 72 h in patients with ADHF and AF, compared with VKA. We hope to facilitate future biomarker-based, large-scale outcome trials using NOACs in patients with ADHF and AF, based on the results of this multicenter, randomized, controlled study.
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Prognostic Factors for Severe Coronavirus Disease 2019 in Daegu, Korea.
Jang, JG, Hur, J, Choi, EY, Hong, KS, Lee, W, Ahn, JH
Journal of Korean medical science. 2020;(23):e209
Abstract
BACKGROUND Since its first detection in December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection has spread rapidly around the world. Although there have been several studies investigating prognostic factors for severe COVID-19, there have been no such studies in Korea. METHODS We performed a retrospective observational study of 110 patients with confirmed COVID-19 hospitalized at a tertiary hospital in Daegu, Korea. Demographic, clinical, laboratory, and outcome data were collected and analyzed. Severe disease was defined as a composite outcome of acute respiratory distress syndrome, intensive care unit care, or death. RESULTS Diabetes mellitus (odds ratio [OR], 19.15; 95% confidence interval [CI], 1.90-193.42; P = 0.012), body temperature ≥ 37.8°C (OR, 10.91; 95% CI, 1.35-88.36; P = 0.025), peripheral oxygen saturation < 92% (OR, 33.31; 95% CI, 2.45-452.22; P = 0.008), and creatine kinase-MB (CK-MB) > 6.3 (OR, 56.84; 95% CI, 2.64-1,223.78, P = 0.010) at admission were associated with higher risk of severe COVID-19. The likelihood of development of severe COVID-19 increased with an increasing number of prognostic factors. CONCLUSION In conclusion, we found that diabetes mellitus, body temperature ≥ 37.8°C, peripheral oxygen saturation < 92%, and CK-MB > 6.3 are independent predictors of severe disease in hospitalized COVID-19 patients. Appropriate assessment of prognostic factors and close monitoring to provide the necessary interventions at the appropriate time in high-risk patients may reduce the case fatality rate of COVID-19.
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Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial.
Sim, M, Kim, CS, Shon, WJ, Lee, YK, Choi, EY, Shin, DM
Scientific reports. 2020;10(1):12130
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Oxidative stress indicates a state where excessive reactive oxygen species (ROS) overwhelm the biological antioxidant capacity, leading to disruption of ROS homeostasis and cellular damage. The aim of this study was to investigate the effects of hydrogen-rich water (HW) consumption in healthy adults through the extensive analyses of antioxidant capacity, peripheral blood mononuclear cell subsets and their transcriptome profile and to compare the effects of HW consumption with those of plain water (PW) consumption. This study is a 4-week, parallel-designed, randomized, double-blind, and placebo-controlled trial. The enrolled participants were randomly assigned to either the PW group (n=19) or the HW group (n=22). Results show that four-week consumption of HW induced a substantial increase in the antioxidant capacity and a decrease in oxidative stress of DNAs, although no significant results were found in the comparison of an intervention (HW) and the placebo (PW) group. Furthermore, the frequencies of apoptotic cells were significantly reduced by HW. Authors conclude that consumption of HW may promote biological antioxidant capacity for adults >30 years more than younger individuals.
Abstract
The evidence for the beneficial effects of drinking hydrogen-water (HW) is rare. We aimed to investigate the effects of HW consumption on oxidative stress and immune functions in healthy adults using systemic approaches of biochemical, cellular, and molecular nutrition. In a randomized, double-blind, placebo-controlled study, healthy adults (20-59 y) consumed either 1.5 L/d of HW (n = 20) or plain water (PW, n = 18) for 4 weeks. The changes from baseline to the 4th week in serum biological antioxidant potential (BAP), derivatives of reactive oxygen, and 8-Oxo-2'-deoxyguanosine did not differ between groups; however, in those aged ≥ 30 y, BAP increased greater in the HW group than the PW group. Apoptosis of peripheral blood mononuclear cells (PBMCs) was significantly less in the HW group. Flow cytometry analysis of CD4+, CD8+, CD20+, CD14+ and CD11b+ cells showed that the frequency of CD14+ cells decreased in the HW group. RNA-sequencing analysis of PBMCs demonstrated that the transcriptomes of the HW group were clearly distinguished from those of the PW group. Most notably, transcriptional networks of inflammatory responses and NF-κB signaling were significantly down-regulated in the HW group. These finding suggest HW increases antioxidant capacity thereby reducing inflammatory responses in healthy adults.
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Prevalence of chronic cough and possible causes in the general population based on the Korean National Health and Nutrition Examination Survey.
Koo, HK, Jeong, I, Lee, SW, Park, J, Kim, JH, Park, SY, Park, HY, Rhee, CK, Kim, YH, Jung, JY, et al
Medicine. 2016;(37):e4595
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Although chronic cough is very common, its prevalence and causes have been rarely reported in the large general population including smokers. This study aimed to identify the prevalence of possible causes of chronic cough and their clinical impact.From Korean National Health and Nutrition Examination Survey (KNHANES) data including 119,280 adults aged over 40 years, 302 individuals with chronic cough were recruited irrespective of smoking status. Data from questionnaire, laboratory tests including spirometry, chest radiographs, and otorhinolaryngologic examination were analyzed.The prevalence of chronic cough in adults was 2.5% ± 0.2%. Current smokers occupied 47.7% ± 3.8% of study population and 46.8% ± 3.9% of the subjects showed upper airway cough syndrome (UACS). Based on spirometry, chronic obstructive pulmonary disease (COPD) was identified in 26.4% ± 3.5%. Asthma explained for 14.5% ± 2.8% of chronic cough. Only 4.1% ± 1.6% showed chronic laryngitis suggesting gastro-esophageal reflux-related cough. Abnormalities on chest radiography were found in 4.0% ± 1.2%. Interestingly, 50.3% ± 4.5% of study subjects had coexisting causes. In multivariate analysis, only current smoking (odds ratio [OR] 3.16, P < 0.001), UACS (OR 2.50, P < 0.001), COPD (OR 2.41, P < 0.001), asthma (OR 8.89, P < 0.001), and chest radiographic abnormalities (OR 2.74, P = 0.003) were independent risk factor for chronic cough. This pattern was not different according to smoking status excepting the prevalence of COPD.Smoking, COPD, and chest radiographic abnormalities should be considered as causes of chronic cough, along with UACS and asthma. Gastro-esophageal reflux-related cough is not prevalent in study population.
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Biochemical and clinical correlation of intraplaque neovascularization using contrast-enhanced ultrasound of the carotid artery.
Kim, HS, Woo, JS, Kim, BY, Jang, HH, Hwang, SJ, Kwon, SJ, Choi, EY, Kim, JB, Cheng, X, Jin, E, et al
Atherosclerosis. 2014;(2):579-583
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Abstract
OBJECTIVE Several biomarkers reflecting inflammatory or proteolytic activity have been known to represent plaque vulnerability. Moreover, a recent study confirmed that contrast-enhanced ultrasound (CEUS) can visualize intraplaque neovascularization (IPN) and demonstrate plaque vulnerability. In this study, we tried to demonstrate that IPN detected by CEUS was correlated with several well-known biomarkers and clinical outcome in patients with coronary artery disease (CAD). METHODS Patients with stable CAD were screened by conventional carotid ultrasound and patients with carotid plaque thickness more than 2 mm were performed by CEUS for the presence of IPN. Plasma levels of biomarkers and clinical outcomes were evaluated. RESULTS Among consecutive 89 patients fulfilled the inclusion criteria, 30 patients without IPN (group 1) and 59 patients with IPN (group 2) were analyzed. There were no significant difference in baseline characteristics except for mean age (62.9±10.1 yrs versus 68.4±9.6 yrs, p=0.015). On multivariate analysis, only MMP-9 (p=0.021, 95% CI 1.002-1.027) showed a significant association with IPN. But patients with IPN showed only trend for a history of cardiovascular disease (CVD) (44% versus 30%, p=0.19) and one-year cardiovascular events (CVE) (6.8% versus 3.3%, p=0.50) compared to group 1. Maximum plaque thickness (p=0.04, 95% CI 1.230-6.322) showed a significant correlation with the clinical outcome including CVD or CVE. CONCLUSION MMP-9 correlated with IPN on CEUS. For clinical implication, however, large prospective studies are needed.
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Resting heart rate as predictor for left ventricular dysfunction and heart failure: MESA (Multi-Ethnic Study of Atherosclerosis).
Opdahl, A, Ambale Venkatesh, B, Fernandes, VRS, Wu, CO, Nasir, K, Choi, EY, Almeida, ALC, Rosen, B, Carvalho, B, Edvardsen, T, et al
Journal of the American College of Cardiology. 2014;(12):1182-1189
Abstract
OBJECTIVES The objective of this study was to investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. BACKGROUND The association of resting heart rate to HF and LV function has not been well described in an asymptomatic multi-ethnic population. METHODS Resting heart rate was measured in participants in the MESA (Multi-Ethnic Study of Atherosclerosis) trial at inclusion. Incident HF was registered (n = 176) during follow-up (median 7 years) in those who underwent cardiac magnetic resonance imaging (n = 5,000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1,056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume, and mass in addition to resting heart rate. RESULTS Cox analysis demonstrated that for 1 beat/min increase in resting heart rate, there was a 4% greater adjusted relative risk for incident HF (hazard ratio: 1.04; 95% CI: 1.02 to 1.06; p < 0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even when all coronary heart disease events were excluded from the model. CONCLUSIONS Elevated resting heart rate was associated with increased risk for incident HF in asymptomatic participants in the MESA trial. Higher heart rate was related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).
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Apoptosis in dilated cardiomyopathy.
Hong, BK, Kwon, HM, Byun, KH, Kim, D, Choi, EY, Kang, TS, Kang, SM, Chun, KJ, Jang, Y, Kim, HS, et al
The Korean journal of internal medicine. 2000;(1):56-64
Abstract
OBJECTIVE Cardiomyopathy, a popular diagnosis that always obscures more than it reveals, nevertheless has several characteristic histological features. These prominently include widespread focal myocardial fibrosis and associated hypertrophy of surviving cardiac myocyte. In fact, focal noninflammatory degeneration (not necrosis) has been demonstrated as a feature of many forms of cardiac hypertrophy. We hypothesized that this loss of myocardial cells in dilated cardiomyopathy (DCMP) may result from cell death by apoptosis. METHODS Endomyocardial biopsy specimens from the right ventricles of six patients who suffered from DCMP were studied, and myocardial specimens from two persons who died in motor vehicle accidents were used as negative controls. For identification of apoptosis, immunohistochemistry with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling was performed. In addition, apoptosis was confirmed morphologically by confocal laser scanning microscopy with propidium iodide. RESULTS Apoptosis, that was represented by an apoptotic index ranging from 19.8 to 25.4%, could be extensively seen in myocytes and also rarely in non-myocytes of interstitium and vascular endothelium. Morphologically, there were a lot of nuclei with clumps of condensed chromatin, suggestive of apoptosis. CONCLUSION The present study demonstrated that myocyte loss in DCMP might be mainly due to the apoptosis of myocytes and interstitial cells, rather than inflammation or cell necrosis.