Trimethylamine N-oxide ameliorates hepatic damage including reduction of hepatic bile acids and cholesterol in Fxr-null mice.

There are conflicting animal experiments on the effect of trimethylamine N-oxide (TMAO), the dietary metabolite, on non-alcoholic fatty liver disease (NAFLD). This study aims to determine the effect of TMAO on NAFLD. A diet containing 0.3% TMAO was fed to farnesoid X receptor (Fxr)-null mice, a model of NAFLD, for 13 weeks. Fxr-null mice fed TMAO showed significant reductions in liver damage markers but not wild-type mice. Hepatic bile acid and cholesterol levels were significantly decreased, and triacylglycerol levels tended to decrease in TMAO-fed Fxr-null mice. Changes in mRNA levels of hepatic bile acid and cholesterol transporters and synthetic enzymes were observed, which could explain the decreased hepatic bile acid and cholesterol levels in Fxr-null mice given the TMAO diet but not in the wild-type mice. These results suggest that TMAO intake ameliorates liver damage in Fxr-null mice, further altering bile acid/cholesterol metabolism in an FXR-independent manner.

Simple risk scoring using sinus rhythm electrocardiograms predicts the incidence of atrial fibrillation in the general population.

Atrial fibrillation (AF) is an arrhythmic disease. Prediction of AF development in healthy individuals is important before serious complications occur. We aimed to develop a risk prediction score for future AF using participants' data, including electrocardiogram (ECG) measurements and information such as age and sex. We included 88,907 Japanese participants, aged 30-69 years, who were randomly assigned to derivation and validation cohorts in a ratio of 1:1. We performed multivariate logistic regression analysis and obtained the standardised beta coefficient of relevant factors and assigned scores to them. We created a score based on prognostic factors for AF to predict its occurrence after five years and applied it to validation cohorts to assess its reproducibility. The risk score ranged from 0 to 17, consisting of age, sex, PR prolongation, QT corrected for heart rate prolongation, left ventricular hypertrophy, premature atrial contraction, and left axis deviation. The area under the curve was 0.75 for the derivation cohort and 0.73 for the validation cohort. The incidence of new-onset AF reached over 2% at 10 points of the risk score in both cohorts. Thus, in this study, we showed the possibility of predicting new-onset AF using ECG findings and simple information.

Association between anthropometric indices and 5-year hypertension incidence in the general Japanese population.

No existing reports demonstrate the association between anthropometric indices (body mass index, waist circumference, body roundness index, a body shape index) and hypertension according to sex and age in the general Japanese population. This retrospective analysis involved individuals aged 30-69 years who underwent annual medical checkups at Kagoshima Koseiren Hospital in 2005-2019, and who did not meet hypertension criteria at baseline. The outcome was hypertension incidence after 5 years, and its association with baseline anthropometric indices was evaluated using multivariable logistic regression analysis by sex and age. In 41,902 participants (age 52.3 ± 10.2 years, 47.7% men), 7622 individuals (18.2%) developed hypertension after 5 years. Body mass index, waist circumference, and body roundness index were significantly associated with the development of hypertension in both men and women across all age categories from 30 s to 60 s. In the population with a body mass index <25 kg/m2, waist circumference and body roundness index were significantly associated with hypertension after 5 years. A body shape index was significantly associated with the development of hypertension in men in their 40 s and 50 s but not in women of any age group. The area under the curve values were lower for a body shape index than for body mass index, waist circumference, and body roundness index in both men and women of all age groups. A body shape index was not a stronger indicator for 5-year hypertension incidence than body mass index, waist circumference, or body roundness index in both men and women across age groups from their 30s-60 s. The results of this study will help to more efficiently identify populations at high risk of developing hypertension and provide preventive interventions. A total of 41,902 participants from health checkup programs were stratified by gender and age to investigate the association between baseline anthropometric indices and hypertension incidence over a 5-year period. BMI, WC, and BRI were almost equally effective and showed a better association with risk of developing hypertension in women and young adults compared to men and old adults. Conversely, ABSI showed no greater association than BMI or WC in any age group in both men and women. ABSI, a body shape index; AUC, area under the curve from receiver operating characteristic curve analysis; BMI, body mass index; BRI, body roundness index; WC, waist circumference.

Cardio-Ankle Vascular Index and Left Atrial Reverse Remodeling After Ablation for Atrial Fibrillation.

Arterial stiffness has been reported to cause left atrial (LA) remodeling due to increased left ventricular filling pressure, resulting in atrial fibrillation (AF). This study aimed to evaluate the association between LA reverse remodeling (LARR) after AF ablation and cardio-ankle vascular index (CAVI), an indicator of arterial stiffness.This study included 333 patients with AF (171 with paroxysmal AF and 162 with nonparoxysmal AF) and LA enlargement (LA volume index ≥ 34 mL/m2) who underwent AF ablation between December 2008 and July 2021. CAVI was evaluated preoperatively during AF (n = 155, 46.5%) or sinus rhythm (n = 178, 53.5%). Participants were divided into groups with LARR (n = 133, 39.9%) and without LARR (n = 200, 60.1%) according to whether the degree of decrease in LA volume index on transthoracic echocardiography 6 months after ablation was ≥ 15% or < 15%, respectively.Sinus rhythm was maintained in 168 (50.5%) patients within 3-6 months after the index procedure. Univariate analysis revealed that preoperative CAVI (7.80 ± 1.22 versus 8.57 ± 1.09, P < 0.001) was significantly lower, and the maintenance of sinus rhythm (61.6% versus 43.0%, P = 0.0011) was higher in the group with LARR. Multivariate logistic regression analysis revealed that preoperative CAVI was independently associated with LARR (odds ratio, 0.60, 95% confidence interval, 0.46-0.78, P < 0.001).In patients with AF and LA enlargement, CAVI is independently associated with LA reverse remodeling after catheter ablation.

Treatment With Small Molecule Inhibitors of Advanced Glycation End-Products Formation and Advanced Glycation End-Products-Mediated Collagen Cross-Linking Promotes Experimental Aortic Aneurysm Progression in Diabetic Mice.

Background Although diabetes attenuates abdominal aortic aneurysms (AAAs), the mechanisms by which diabetes suppresses AAAs remain incompletely understood. Accumulation of advanced glycation end- (AGEs) reduces extracellular matrix (ECM) degradation in diabetes. Because ECM degradation is critical for AAA pathogenesis, we investigated whether AGEs mediate experimental AAA suppression in diabetes by blocking AGE formation or disrupting AGE-ECM cross-linking using small molecule inhibitors. Methods and Results Male C57BL/6J mice were treated with streptozotocin and intra-aortic elastase infusion to induce diabetes and experimental AAAs, respectively. Aminoguanidine (AGE formation inhibitor, 200 mg/kg), alagebrium (AGE-ECM cross-linking disrupter, 20 mg/kg), or vehicle was administered daily to mice from the last day following streptozotocin injection. AAAs were assessed via serial aortic diameter measurements, histopathology, and in vitro medial elastolysis assays. Treatment with aminoguanidine, not alagebrium, diminished AGEs in diabetic AAAs. Treatment with both inhibitors enhanced aortic enlargement in diabetic mice as compared with vehicle treatment. Neither enhanced AAA enlargement in nondiabetic mice. AAA enhancement in diabetic mice by aminoguanidine or alagebrium treatment promoted elastin degradation, smooth muscle cell depletion, mural macrophage accumulation, and neoangiogenesis without affecting matrix metalloproteinases, C-C motif chemokine ligand 2, or serum glucose concentration. Additionally, treatment with both inhibitors reversed suppression of diabetic aortic medial elastolysis by porcine pancreatic elastase in vitro. Conclusions Inhibiting AGE formation or AGE-ECM cross-linking enhances experimental AAAs in diabetes. These findings support the hypothesis that AGEs attenuate experimental AAAs in diabetes. These findings underscore the potential translational value of enhanced ECM cross-linking as an inhibitory strategy for early AAA disease.

Genetic deficiency of protein inhibitor of activated STAT3 suppresses experimental abdominal aortic aneurysms.

Aim: Signal transducer and activator of transcription (STAT) signaling is critical for the pathogenesis of abdominal aortic aneurysms (AAAs). Though protein inhibitor of activated STAT3 (PIAS3) negatively modulates STAT3 activity, but its role in AAA disease remains undefined. Method: AAAs were induced in PIAS3 deficient (PIAS3-/-) and wild type (PIAS3+/+) male mice via transient intra-aortic elastase infusion. AAAs were assessed by in situ measurements of infrarenal aortic external diameters prior to (day 0) and 14 days after elastase infusion. Characteristic aneurysmal pathologies were evaluated by histopathology. Results: Fourteen days following elastase infusion, aneurysmal aortic diameter was reduced by an approximately 50% in PIAS3-/- as compared to PIAS3+/+ mice. On histological analyses, PIAS3-/- mice showed less medial elastin degradation (media score: 2.5) and smooth muscle cell loss (media score: 3.0) than those in PIAS3+/+ mice (media score: 4 for both elastin and SMC destruction). Aortic wall leukocyte accumulation including macrophages, CD4+ T cells, CD8+ T cells and B cells as well as mural neovessel formation were significantly reduced in PIAS3-/- as compared to PIAS3+/+ mice. Additionally, PIAS3 deficiency also downregulated the expression levels of matrix metalloproteinases 2 and 9 by 61% and 70%, respectively, in aneurysmal lesion. Conclusion: PIAS3 deficiency ameliorated experimental AAAs in conjunction with reduced medial elastin degradation and smooth muscle cell depletion, mural leukocyte accumulation and angiogenesis.

Development of predictive equation and score for 5-year metabolic syndrome incidence in Japanese adults.

BACKGROUND: Predicting metabolic syndrome (MetS) is important for identifying high-risk cardiovascular disease individuals and providing preventive interventions. We aimed to develop and validate an equation and a simple MetS score according to the Japanese MetS criteria. METHODS: In total, 54,198 participants (age, 54.5±10.1 years; men, 46.0%), with baseline and 5-year follow-up data were randomly assigned to 'Derivation' and 'Validation' cohorts (ratio: 2:1). Multivariate logistic regression analysis was performed in derivation cohort and scores were assigned to factors corresponding to ß-coefficients. We evaluated predictive ability of the scores using area under the curve (AUC), then applied them to validation cohort to assess reproducibility. RESULTS: The primary model ranged 0-27 points had an AUC of 0.81 (sensitivity: 0.81, specificity: 0.81, cut-off score: 14), and consisted of age, sex, blood pressure (BP), body mass index (BMI), serum lipids, glucose measurements, tobacco smoking, and alcohol consumption. The simplified model (excluding blood tests) ranged 0-17 points with an AUC of 0.78 (sensitivity: 0.83, specificity: 0.77, cut-off score: 15) and included: age, sex, systolic BP, diastolic BP, BMI, tobacco smoking, and alcohol consumption. We classified individuals with a score <15 and ≥15 points as low- and high-risk MetS, respectively. Furthermore, the equation model generated an AUC of 0.85 (sensitivity: 0.86, specificity: 0.55). Analysis of the validation and derivation cohorts yielded similar results. CONCLUSION: We developed a primary score, an equation model, and a simple score. The simple score is convenient, well-validated with acceptable discrimination, and could be used for early detection of MetS in high-risk individuals.

Clinical significance of atherosclerotic risk factors differs in early and advanced stages of plaque formation: A longitudinal study in the general population.

BACKGROUND: Carotid plaque is a well-known prognostic factor for cardiovascular diseases. It is unclear which risk factors are associated with the transformation of carotid plaque over time. In this longitudinal study, we examined the risk factors related to carotid plaque progression. METHODS: We enrolled 738 men without medication (mean age: 55 ± 10 years) who underwent the first and second health examinations. We measured carotid plaque thickness (PT) at three points of the right and left carotid artery. Plaque score (PS) was calculated by summing all the PTs. We divided the PS into three groups: None-group (PS <1.1), Early-group (1.1 ≤ PS <5.1), and Advanced-group (PS ≥5.1). We analyzed the relationship between PS progression and parameters such as age, body mass index, systolic blood pressure (SBP), fasting blood sugar, low-density lipoprotein cholesterol (LDL-C), and smoking and exercise habits. RESULTS: In multivariable logistic regression analysis, age and SBP were independent factors for PS progression from none to early stages (age, OR 1.07, p = 0.002; SBP, 10 mmHg, OR 1.27, p = 0.041). Age, follow-up period and LDL-C were independently associated factors for PS progression from early to advanced stages (age, OR 1.08,p < 0.001; follow-up period OR1.19, p = 0.041; LDL-C, 10 mg/dL, OR 1.10, p = 0.049). CONCLUSIONS: SBP was independently associated with the progress of early atherosclerosis, while LDL-C was independently associated with the progression of advanced atherosclerosis in the general population. Further studies are needed to assess whether early control of SBP and LDL-C levels can reduce the occurrence of future cardiovascular events.

The soothing effect of phlorotannins on cedar pollinosis in Cry j 1-stimulated mice.

The antiallergic properties of phlorotannins, algal polyphenols, have been widely reported. This study examined the soothing effect of phlorotannin concentrate (PTC) from Eisenia nipponica on cedar pollinosis in Cry j 1-stimulated mice. PTC reduced the mice's sneezing and nasal rubbing, which was attributed to decreased levels of immunoglobulin E and Th2-type cytokines [interleukin (IL)-4, IL-5, and IL-13].

Prognostic predictors in patients with cardiopulmonary arrest: A novel equation for evaluating the 30-day mortality.

BACKGROUND: Early prediction of outcomes after cardiopulmonary arrest (CPA) is important for considering the best support. Our purpose was to evaluate predictors of the 30-day mortality in patients with CPA after return of spontaneous circulation (ROSC) and to assess an equation for calculating the 30-day mortality using clinical parameters. METHODS: We retrospectively analyzed the data of 194 consecutive patients with CPA and ROSC in a derivation study (2015-2022). We compared clinical parameters between the survived (n = 78) and dead (n = 116) patients. We derived an equation for estimated probability of death based on clinical parameters, using multivariate logistic regression analysis. The reliability of the equation was validated in 80 additional patients with CPA. RESULTS: The 30-day mortality was associated with sex, witnessed cardiac arrest, bystander cardiopulmonary resuscitation (CPR), CPA due to acute myocardial infarction, pupil diameter, Glasgow Coma Scale score (GCS), presence of light reflex, arterial or venous pH, lactate levels, initial ventricular fibrillation (VF), CPA time, and age. The derived logistic regression equation was as follows: Estimated probability of death = 1 / (1 + e-x), x = (0.25 × bystander CPR) + (0.44 × pupil diameter) - (0.14 × GCS) + (0.09 × lactate) - (1.87 × initial VF) + (0.07 × CPA time) + (0.05 × age) - 7.03. The cut-off value for estimated probability of death calculated by this equation was 54.5 %, yielding a sensitivity, specificity, and accuracy of 86.2 %, 80.8 %, and 84.5 %, respectively. In the validation model, these values were 81.8 %, 85.7 %, and 82.5 %, respectively. CONCLUSIONS: The 30-day mortality may be calculated after ROSC in patients with CPA using simple clinical parameters. This equation may facilitate further best support for patients with CPA.

Cutoff Values of Brachial-Ankle Pulse Wave Velocity for Atherosclerotic Risks by Age and Sex in the Japanese General Population.

AIM: In this study, we aim to analyze the correlation between brachial-ankle pulse wave velocity (baPWV) and Suita score or Framingham risk score and obtain the cutoff value of baPWV by sex and age for cardiovascular risk, as assessed by these scores in the large Japanese annual health checkup data. METHODS: In total, 25,602 participants (14,539 men and 11,063 women), who had their annual health checkups, were included in this study. Cutoff values of baPWV for the moderate- and high-risk groups stratified by sex and age were obtained using a receiver operating characteristic (ROC) curve analysis. RESULTS: As per our findings, the Suita score demonstrated better correlations with baPWV than the Framingham risk score in both sexes (men, Suita score R2=0.41 and Framingham risk score R2=0.37; women, Suita score R2=0.54 and Framingham risk score R2=0.33). The ROC curve analysis demonstrated the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score, and they are as follows: in men, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,520 cm/s in the 60s, and 1,880 cm/s in the 70s. In women, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,570 cm/s in the 60s, and 1,800 cm/s in the 70s. CONCLUSIONS: We demonstrated that baPWV significantly correlated with the Suita score or Framingham risk score in both men and women, with the former presenting a stronger correlation than the latter. We propose the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score.

Social Frailty and Meaningful Activities among Community-Dwelling Older Adults with Heart Disease.

Patients with heart disease are more likely to experience social frailty due to physical inactivity, which may affect meaningful activities such as hobbies. This study aimed to investigate (1) the association between heart disease and social frailty in community-dwelling older adults and (2) the characteristics of meaningful activities in community-dwelling older adults with heart disease. Data from 630 older adults who participated in a community-based health survey were obtained, including clinical history, meaningful activities, social frailty and psychosomatic functions. Participants were divided into two groups: those with heart disease (n = 79) and those without (n = 551), and comparisons were made. Social frailty was observed in 23.7% of participants with heart disease, and logistic regression revealed significant associations with heart disease and social frailty after adjusting for potential covariates (OR, 1.97; 95% CI, 1.06 3.67; p = 0.032). Participants with heart disease did not differ significantly in terms of satisfaction or performance; their frequency of engagement in meaningful activities was significantly lower than without heart disease (p = 0.041). These results suggest that heart disease and social frailty are associated in community-dwelling older adults, and that this demographic is inclined to engage in meaningful activities less frequently.

Insufficient blood pressure control is independently associated with increased arterial stiffness.

Hypertension is a risk factor for atherosclerosis. Achieving the therapeutic target value of blood pressure (BP) prevents the onset of cardiovascular events; however, it is not clear how antihypertensive drug use and BP control status relate to arterial stiffness. The purpose of this study is to investigate the relationship between BP control status with or without antihypertensive drugs and arterial stiffness. Nine hundred eighty individuals (mean age: 68 ± 11 years) who participated in a community-based cohort study were enrolled. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). Higher BP was defined as a systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Participants were divided into four groups: normal, non higher BP without antihypertensive drugs (n = 421); untreated, higher BP without antihypertensive drugs (n = 174); good control, non higher BP with antihypertensive drugs (n = 209); and poor control, higher BP with antihypertensive drugs (n = 176). In multivariable logistic analysis adjusted for age, sex, dyslipidemia and diabetes mellitus medication use, obesity, smoking, alcohol drinking, and heart rate at the CAVI measurement for a high CAVI-using a borderline cutoff value of 8.0-the other three groups were significantly associated with a high CAVI when compared with the normal group. By contrast, multivariable logistic analysis of a high CAVI using an abnormal cutoff value of 9.0 demonstrated that the poor control and untreated groups were significantly associated with a high CAVI, whereas the good control group was not. In conclusion, even with antihypertensive drugs, poor BP control is independently associated with a high CAVI.

Association of blood pressure and dietary intake of Sunomono, Japanese vinegared side dishes, in community-dwelling Japanese: A cross-sectional study.

Objective: Vinegar has been reported to have a hypotensive effect. We aimed to investigate the relationship between the consumption of vinegar-based side dishes and blood pressure. Research methods & procedures: This cross-sectional study included 746 individuals (257 men and 489 women) aged ≥40 years from Tarumizu, Kagoshima, Japan. Nutrient intake was estimated based on the brief-type self-administered diet history questionnaire. The intake frequency of vinegar-based side dishes (Sunomono and pickles) was determined using a self-administered diet history questionnaire. Participants who did not consume vinegar-based side dishes for a month were defined as having no Sunomono or pickle eating habit. Blood pressure was categorized into four groups according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension. The association between the intake of vinegar-based side dishes and blood pressure categories was analyzed using ordinal logistic regression analysis adjusted for age, body mass index, smoking history, excessive alcohol intake, living situation, energy intake, protein intake, sodium intake, potassium intake, and seaweed intake. Results: Approximately 13.6% men and 6.1% women had no Sunomono eating habits. In men, eating Sunomono, but not pickles, was significantly related to blood pressure categories (estimate, -0.702; 95% CI, -1.122 to -0.310), whereas more frequent consumption of Sunomono did not show an improvement in the blood pressure category. The relationship between eating Sunomono and blood pressure categories was not recognized in women. Conclusion: This was the first study assessing the association between consumption of vinegar-based side dishes and blood pressure categories. We highlighted the effect of Sunomono consumption on blood pressure categories in men. Consumption of Sunomono may improve blood pressure in men.

Estimation of the Risk of Postoperative Hypertension Following Minor to Moderate Surgery Using an Echocardiogram and Biomarkers.

This study aimed to determine independent factors for developing postoperative hypertension using 4 biomarkers in patients receiving oral and maxillofacial surgery under general anesthesia. Brain natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity myocardial troponin T (hs-TnT), and high-sensitivity myocardial troponin I (hs-TnI) were measured and preoperative echocardiograms were examined. Episodes of systolic blood pressure (SBP) ≥ 170 mmHg or diastolic blood pressure ≥ 100 mmHg within 1 week after surgery were considered postoperative hypertension. We analyzed 213 (130 men; 83 women) patients, who were divided into a postoperative hypertension group (HT group, n = 32) and a normal group (N group, n = 181). The HT group showed a higher LVMI (113.5 versus 100.1), higher E/e' of the lateral wall (9.1 versus 7.7), and higher BNP (39.2 versus 22.9 pg/mL), NT-proBNP (400.1 versus 143.9 pg/mL), and hs-TnT (15.6 versus 10.3 ng/L) concentrations compared to the N group. NT-proBNP and hs-TnT concentrations positively associated with E/e', but BNP and hs-TnI did not. NT-proBNP (AUC = 0.64, cutoff value: 117.0 pg/mL) and hs-TnT (AUC = 0.61, cutoff value: 11.0 ng/L) concentrations were effective for discriminating E/e' ≥ 12. Multivariate logistic regression analyses showed that risk factors responsible for developing postoperative hypertension were NT-proBNP and hs-TnT using biomarkers and E/e' as independent variables, and NT-proBNP and SBP at admission using biomarkers and SBP at admission as independent variables. These findings suggest that NT-proBNP and hs-TnT concentrations, and SBP at admission, are useful to predict postoperative hypertension after minor to moderate surgery, and that left ventricular filling pressure is a primary factor associated with postoperative hypertension.

Association of Sleep Duration and Cardio-Ankle Vascular Index in Community-Dwelling Older Adults.

AIM: This study aims to investigate the association of the Cardio-Ankle Vascular Index (CAVI) with self-reported sleep duration and sleep quality in community-dwelling older adults aged ≥ 65 years. METHODS: The Tarumizu Study was a cohort of community-based health checkups conducted in the Tarumizu City, Japan, in 2018 and 2019. In total, 997 participants aged ≥ 65 years (median age, 74 years) were examined. We obtained the average sleep duration and sleep quality using self-reported questionnaires and classified them into three separate groups according to sleep duration (＜6 h, 6-8 h, and ≥ 8 h) and sleep quality (good, medium, and poor). The arterial stiffness was measured using the CAVI. RESULTS: As per our findings, the CAVI was significantly higher in the ≥ 8 h sleep group (CAVI=9.6±1.3) than in the ＜6 h (CAVI=9.1±1.1) or 6-8 h (CAVI=9.1±1.2) groups (p＜0.001). After adjustment for age, sex, systolic blood pressure, current smoking status, body mass index, frequency of exercise, educational background, frailty, sleep medication, sleep quality, and nap duration, multivariable regression analysis demonstrated that the CAVI was significantly higher in the ≥ 8 h group than in the 6-8 h group (p=0.016). In contrast, multivariable regression analysis showed that there was no significant association between sleep quality and CAVI. CONCLUSIONS: A significant association was noted between long sleep duration (≥ 8 h) and elevated CAVI in community-dwelling older adults aged ≥ 65 years. We, therefore, suggest that long sleep duration, not sleep quality, is correlated with arterial stiffness in older adults.

The Immunomodulating Effect of Phlorotannins from a Brown Alga, Eisenia nipponica, on Mice Stimulated with Ovalbumin through T Cell Regulation.

The immunomodulating effect of phlorotannin was investigated in mice stimulated by ovalbumin. When analyzing the main components of phlorotannin concentrate (PTC) from Eisenia nipponica, seven phlorotannins [eckol, 6,6'-bieckol, 6,8'-bieckol, 8,8'-bieckol, dieckol, phlorofucofuroeckol (PFF)-A, and PFF-B] were detected. These phlorotannins accounted for approximately 80% of PTC. Oral administration of PTC to mice daily for 21 days reduced serum immunoglobulin E (IgE) and total IgG1 levels attributable to Th2 cells. The production of splenic cytokines [interleukin (IL)-10 and transforming growth factor-ß1] and Treg cell-mediated expression of forkhead box protein P3 mRNA were significantly increased whereas the production of inflammatory cytokines (interferon-γ, IL-4, IL-5, and IL-17) by Th1, Th2, and Th17 cells was markedly suppressed. IL-21 production and basic leucine zipper ATF-like transcription factor mRNA expression attributable to follicular helper T (Tfh) cells were also suppressed. Flow cytometric analyses demonstrated increased number of Treg cells despite a decrease in the total T cell population. An increase in total B cells was also observed by the flow cytometric analyses in addition to increases in IL-10 production, which activates B cells. In contrast, the significantly suppressed production of inflammatory cytokines and moderate increase in Treg cell subpopulation indicated a direct impact of PTC on inflammatory lymphocytes (Th1, Th2, Th17, and Tfh). Thus, PTC may exert antiallergic effects by immunomodulation of T cells and inactivation of inflammatory lymphocyte.

Decrease in red cell distribution width as a useful predictor of success after catheter ablation for atrial fibrillation: a retrospective multi-center study.

Red cell distribution width (RDW) is reportedly associated with cardiovascular events, including atrial fibrillation (AF). We investigated whether the RDW values were associated with the outcomes of catheter ablation for AF. This retrospective multicenter study included 501 patients with AF (239 paroxysmal AF cases, 196 persistent AF cases, and 66 long-standing persistent AF cases) who underwent initial AF ablation between March 2017 and May 2018. The RDW values were evaluated before and at 1-3 months after the procedure. The patients were stratified based on the recurrence of AF within 1 year after the index procedure with a blanking period of 3 months into recurrence group (107 patients, 21.4%) and no-recurrence group (394 patients, 78.6%). There were no significant differences in preoperative RDW values between the groups (p = 0.37). The RDW value did not change significantly after the ablation in the recurrence group (13.55-13.60%, p = 0.37), although it decreased significantly in the no-recurrence group (13.64-13.37%, p < 0.001). Multivariate Cox proportional hazards regression analyses revealed that a postoperative change in RDW (ΔRDW) was independently associated with AF recurrence (hazard ratio 2.00, 95% confidence interval 1.42-2.76, p < 0.001). Receiver operating characteristic curve analysis revealed that a ΔRDW cut-off value of - 0.1% provided a c-statistic of 0.65 for predicting AF recurrence. Decrease in RDW during the blanking period after ablation independently predicted the 1-year success of AF ablation.