Search

Isorhamnetin, a natural flavonoid, has strong antioxidant and antifibrotic effects, and a regulatory effect against Ca2+-handling. Atrial remodeling due to fibrosis and abnormal intracellular Ca2+ activities contributes to initiation and persistence of atrial fibrillation (AF). The present study investigated the effect of isorhamnetin on angiotensin II (AngII)-induced AF in mice. Wild-type male mice (C57BL/6J, 8 weeks old) were assigned to three groups: (1) control group, (2) AngII-treated group, and (3) AngII- and isorhamnetin-treated group. AngII (1000 ng/kg/min) and isorhamnetin (5 mg/kg) were administered continuously via an implantable osmotic pump for two weeks and intraperitoneally one week before initiating AngII administration, respectively. AF induction and electrophysiological studies, Ca2+ imaging with isolated atrial myocytes and HL-1 cells, and action potential duration (APD) measurements using atrial tissue and HL-1 cells were performed. AF-related molecule expression was assessed and histopathological examination was performed. Isorhamnetin decreased AF inducibility compared with the AngII group and restored AngII-induced atrial effective refractory period prolongation. Isorhamnetin eliminated abnormal diastolic intracellular Ca2+ activities induced by AngII. Isorhamnetin also abrogated AngII-induced APD prolongation and abnormal Ca2+ loading in HL-1 cells. Furthermore, isorhamnetin strongly attenuated AngII-induced left atrial enlargement and atrial fibrosis. AngII-induced elevated expression of AF-associated molecules, such as ox-CaMKII, p-RyR2, p-JNK, p-ERK, and TRPC3/6, was improved by isorhamnetin treatment. The findings of the present study suggest that isorhamnetin prevents AngII-induced AF vulnerability and arrhythmogenic atrial remodeling, highlighting its therapeutic potential as an anti-arrhythmogenic pharmaceutical or dietary supplement.

Background and Purpose: Isorhamnetin, a natural flavonoid, has strong antioxidant and anti-fibrotic effects, and a regulatory effect against Ca2+-handling. Atrial remodeling due to fibrosis and abnormal intracellular Ca2+ activities contributes to initiation and persistence of atrial fibrillation (AF). This study investigated the effect of isorhamnetin on angiotensin II (AngII)-induced AF in mice. Experimental Approach: Wild-type male mice (C57BL/6J, 8 weeks old) were assigned to three groups: (1) control group, (2) AngII-treated group, and (3) AngII-and isorhamnetin-treated groups. AngII (1000 ng/kg/min) and isorhamnetin (5 mg/kg) were administered continuously via an implantable osmotic pump for two weeks and intraperitoneally one week before initiating AngII administration, respectively. AF induction and electrophysiological studies, Ca2+ imaging with isolated atrial myocytes and HL-1 cells, and action potential duration (APD) measurements using HL-1 cells were performed. AF-related molecule expression was assessed and histopathological examination was performed. Key Results: Isorhamnetin decreased AF inducibility compared to the AngII group and restored AngII-induced atrial effective refractory period prolongation. Isorhamnetin eliminated abnormal diastolic intracellular Ca2+ activities induced by AngII. Isorhamnetin also abrogated AngII-induced APD prolongation and abnormal Ca2+ loading in HL-1 cells. Furthermore, isorhamnetin strongly attenuated AngII-induced left atrial enlargement and atrial fibrosis. AngII-induced elevated expression of AF-associated molecules, such as ox-CaMKII, p-RyR2, p-JNK, p-ERK, and TRPC3/6, was improved by isorhamnetin treatment. Conclusion and Implications: The findings of this study suggest that isorhamnetin prevents AngII-induced AF vulnerability and arrhythmogenic atrial remodeling via modulating CaMKII-RyR2 and TRPC-mediated MAPK pathways, highlighting its potential as an anti-arrhythmogenic pharmaceutical or dietary supplement.

Dilated cardiomyopathy (DCM) remains among the most refractory heart diseases because of its complicated pathogenesis, and the key molecules that cause it remain unclear.To elucidate the molecules and upstream pathways critical for DCM pathogenesis, we performed meta-analysis and co-expression analysis of RNA-sequencing (RNA-seq) datasets from publicly available databases. We analyzed three RNA-seq datasets containing comparisons of RNA expression in left ventricles between healthy controls and DCM patients. We extracted differentially expressed genes (DEGs) and clarified upstream regulators of cardiovascular disease-related DEGs by Ingenuity Pathway Analysis (IPA). Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) analysis were also used to identify the hub gene candidates strongly associated with DCM.In total, 406 samples (184 healthy, 222 DCM) were used in this study. Overall, 391 DEGs [absolute fold change (FC) ≥ 1.5; P 0.01], including 221 upregulated and 170 downregulated ones in DCM, were extracted. Seven common hub genes (LUM, COL1A2, CXCL10, FMOD, COL3A1, ADAMTS4, MRC1) were finally screened. IPA showed several upstream transcriptional regulators, including activating (NFKBIA, TP73, CALR, NFKB1, KLF4) and inhibiting (CEBPA, PPARGC1A) ones. We further validated increased expression of several common hub genes in the transverse aortic constriction-induced heart failure model.In conclusion, meta-analysis and WGCNA using RNA-seq databases of DCM patients identified seven hub genes and seven upstream transcriptional regulators.

This paper proposes a touch panel interface to support an explanation of pains by choosing options. Medical staffs of rehabilitation must understand pain information of patients. Patients would explain their pains with words and gestures. The explanation of pain depends on the expression of the patient. If the patient does not explain his/her pains accurately, the medical staff may not have enough treatment for the patient. The proposed interface provides patients with support to explain their pains. The users input four types of pain information: the occurring condition, the part of the body, the feeling of pain, and the degree of pain. The four types of information can be input by choosing options. The interface users can explain their pains regardless of their vocabulary. We carried out an experiment to verify the efficiency of the proposed interface. We found that the proposed interface could support users to explain their pains.

Oxidative stress could be a possible mechanism and a therapeutic target of atrial fibrillation (AF). However, the effects of the xanthine oxidase (XO) inhibition for AF remain to be fully elucidated. We investigated the effects of a novel XO inhibitor febuxostat on AF compared with allopurinol in hypertension rat model. Five-week-old Dahl salt-sensitive rats were fed either low-salt (LS) (0.3% NaCl) or high-salt (HS) (8% NaCl) diet. After 4 weeks of diet, HS diet rats were divided into three groups: orally administered to vehicle (HS-C), febuxostat (5 mg/kg/day) (HS-F), or allopurinol (50 mg/kg/day) (HS-A). After 4 weeks of treatment, systolic blood pressure (SBP) was significantly higher in HS-C than LS, and it was slightly but significantly decreased by treatment with each XO inhibitor. AF duration was significantly prolonged in HS-C compared with LS, and significantly suppressed in both HS-F and HS-A (LS; 5.8 ± 3.5 s, HS-C; 33.9 ± 23.7 s, HS-F; 15.0 ± 14.1 s, HS-A; 20.1 ± 11.9 s: P

Programmed death ligand 2 (PD-L2) is the second ligand of programmed death 1 (PD-1) protein. In autoimmune myocarditis, the protective roles of PD-1 and its first ligand programmed death ligand 1 (PD-L1) have been well documented, however, the role of PD-L2 remains unknown. In this study, we report that PD-L2 deficiency exacerbates myocardial inflammation in mice with experimental autoimmune myocarditis (EAM). EAM was established in wild-type (WT) and PD-L2-deficient mice by immunization with murine cardiac myosin peptide. We found that PD-L2-deficient mice had more serious inflammatory infiltration in the heart and a significantly higher myocarditis severity score than WT mice. PD-L2-deficient dendritic cells (DCs) enhanced CD4+ T cell proliferation in the presence of T cell receptor and CD28 signaling. These data suggest that PD-L2 on DCs protects against autoreactive CD4+ T cell expansion and severe inflammation in mice with EAM.

Aging and obesity are the most prominent risk factors for onset of atrial fibrillation (AF). Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme that catalyzes nicotinamide adenine dinucleotide (NAD) activity. Nampt and NAD are essential for maintenance of cellular redox homeostasis and modulation of cellular metabolism, and their expression levels decrease with aging and obesity. However, a role for Nampt in AF is unknown. The present study aims to test whether there is a role of Nampt/NAD axis in the pathogenesis of obesity-induced AF. Male C57BL/6J (WT) mice and heterozygous Nampt knockout (NKO) mice were fed with a normal chow diet (ND) or a high-fat diet (HFD). Electrophysiological study showed that AF inducibility was significantly increased in WT+HFD, NKO+ND, and NKO+HFD mice compared with WT+ND mice. AF duration was significantly longer in WT+HFD and NKO+ND mice and further prolonged in NKO+HFD mice compared with WT+ND mice and the calcium handling pathway was altered on molecular level. Also, treatment with nicotinamide riboside, a NAD precursor, partially restored the HFD-induced AF perpetuation. Overall, this work demonstrates that partially deletion of Nampt facilitated HFD-induced AF through increased diastolic calcium leaks. The Nampt/NAD axis may be a potent therapeutic target for AF.

Macrophages are fundamental components of inflammation in post‐myocardial infarction (MI) and contribute to adverse cardiac remodelling and heart failure. However, the regulatory mechanisms in macrophage activation have not been fully elucidated. Previous studies showed that myeloid‐associated immunoglobulin–like receptor II (MAIR‐II) is involved in inflammatory responses in macrophages. However, its role in MI is unknown. Thus, this study aimed to determine a novel role and mechanism of MAIR‐II in MI. We first identified that MAIR‐II–positive myeloid cells were abundant from post‐MI days 3 to 5 in infarcted hearts of C57BL/6J (WT) mice induced by permanent left coronary artery ligation. Compared to WT, MAIR‐II–deficient (Cd300c2 −/−) mice had longer survival, ameliorated cardiac remodelling, improved cardiac function and smaller infarct sizes. Moreover, we detected lower pro‐inflammatory cytokine and fibrotic gene expressions in Cd300c2 −/−‐infarcted hearts. These mice also had less infiltrating pro‐inflammatory macrophages following MI. To elucidate a novel molecular mechanism of MAIR‐II, we considered macrophage activation by Toll‐like receptor (TLR) 9–mediated inflammation. In vitro, we observed that Cd300c2 −/− bone marrow–derived macrophages stimulated by a TLR9 agonist expressed less pro‐inflammatory cytokines compared to WT. In conclusion, MAIR‐II may enhance inflammation via TLR9‐mediated macrophage activation in MI, leading to adverse cardiac remodelling and poor prognosis.

We call a positive integer N a 4-perfect number if the sum of all divisors of N is equal to 4N. In this paper, we give some sufficient conditions such that an odd integer exactly divisible by \(3^2\) cannot be 4-perfect. Moreover, we refine Euler’s structure theorem on odd 4-perfect numbers given by Broughan and Zhou in the case where N is exactly divisible by \(3^2\).

A 71-year-old woman was admitted with dyspnea. An electrocardiogram revealed ST-segment elevation, and echocardiography showed akinesis in the left ventricular apex with hyperkinesis of the base. Coronary angiography revealed no stenosis, and left ventriculography indicated ballooning of the left ventricular apex and apical ventricular septal perforation. We diagnosed the patient with Takotsubo syndrome complicated by ventricular septal perforation, which was surgically repaired. Although ventricular septal perforation is recognized as a life-threatening complication after acute myocardial infarction, it can also occur after Takotsubo syndrome. The early recognition and management of this condition can help prevent morbidity and mortality.

Aging and obesity are the most prominent risk factors for onset of atrial fibrillation (AF). Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme that catalyzes nicotinamide adenine dinucleotide (NAD) activity. Nampt and NAD are essential for maintenance of cellular redox homeostasis and modulation of cellular metabolism, and their expression levels decrease with aging and obesity. However, a role for Nampt in AF is unknown. The present study aims to test whether there is a role of Nampt/NAD axis in the pathogenesis of obesity-induced AF. Male C57BL/6J (WT) mice and heterozygous Nampt knockout (NKO) mice were fed with a normal chow diet (ND) or a high-fat diet (HFD). Electrophysiological study showed that AF inducibility was significantly increased in WT+HFD, NKO+ND, and NKO+HFD mice compared with WT+ND mice. AF duration was significantly longer in WT+HFD and NKO+ND mice and further prolonged in NKO+HFD mice compared with WT+ND mice and the calcium handling pathway was altered on molecular level. Also, treatment with nicotinamide riboside, a NAD precursor, partially restored the HFD-induced AF perpetuation. Overall, this work demonstrates that partially deletion of Nampt facilitated HFD-induced AF through increased diastolic calcium leaks. The Nampt/NAD axis may be a potent therapeutic target for AF.

A natural pigment, anthocyanin, extracted from purple sweet potato was complexed with smectite group layered clay minerals, a synthetic saponite and a natural montmorillonite. The resulting biohybrid with the synthetic saponite exhibited a clear color change between blue and pink upon exposure to acidic (HCl) and basic (ammonia) vapors. The color change is similar to that of anthocyanin molecule in solution which is due to the change in the molecular structure of anthocyanin. The response for the color change was within 10 min upon exposure to the vapors and was reversible. The present biohybrid composed of environmentally benign chemically stable and non toxic components is regarded as a possible candidate of environmental sensors and smart pigments.

Neutrophils are recruited into the heart at an early stage following a myocardial infarction (MI). These secrete several proteases, one of them being neutrophil elastase (NE), which promotes inflammatory responses in several disease models. It has been shown that there is an increase in NE activity in patients with MI, however, the role of NE in MI remains unclear. Therefore, the present study aimed to investigate the role of NE in the pathogenesis of MI in mice. NE expression peaked on day 1 in the infarcted hearts. In addition, NE deficiency improved survival and cardiac function post-MI, limiting fibrosis in the noninfarcted myocardium. Sivelestat, an NE inhibitor, also improved survival and cardiac function post-MI. Flow cytometric analysis showed that the numbers of heart-infiltrating neutrophils and inflammatory macrophages (CD11b+F4/80+CD206low cells) were significantly lower in NE-deficient mice than in wild-type (WT) mice. At the border zone between intact and necrotic areas, the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells was lower in NE-deficient mice than in WT mice. Western blot analyses revealed that the expression levels of insulin receptor substrate 1 and phosphorylation of Akt were significantly upregulated in NE-knockout mouse hearts, indicating that NE deficiency might improve cardiac survival by upregulating insulin/Akt signaling post-MI. Thus, NE may enhance myocardial injury by inducing an excessive inflammatory response and suppressing Akt signaling in cardiomyocytes. Inhibition of NE might serve as a novel therapeutic target in the treatment of MI.

Objectives This study sought to determine the feasibility of a novel simplified ablation protocol targeting only the pulmonary vein antrum using the radiofrequency hot-balloon catheter in patients with paroxysmal atrial fibrillation. Background Radiofrequency hot-balloon (RHB) catheter has been recently introduced into clinical practice for pulmonary vein isolation (PVI). The authors hypothesized that a novel simplified ablation protocol targeting only the PV antrum with energy application for a longer time (single-shot technique) could be an alternative approach to achieve PVI, while avoiding unnecessary energy application at the PV ostium. Methods A total of 61 consecutive paroxysmal atrial fibrillation patients (age 64.1 ± 10.9 years, 48 male) who underwent antrum RHB-PVI were enrolled. Energy applications were performed following the pre-specified protocol only targeting the PV antrum. If the PVI was not achieved after 2 energy applications using the RHB, a touch-up ablation was performed. Results Of 241 PV, including 3 left common PV, 194 (80%) were isolated exclusively using the RHB. The target PVI average per group of 15 consecutive procedures improved from 75% (initial 15) to 89% (last 16) of patients. The injected volume was greatest in the right superior PV (13.1 ± 2.0 ml) and the smallest in the left inferior PV (10.8 ± 1.1 ml), and 23 PV (9.5%) required over 15 ml (estimated balloon diameter of 30 mm). Periprocedural complications were noted in 3 patients (4.9%), but phrenic nerve injury was not observed. Sinus rhythm maintenance at 12-month follow-up was achieved in 57 patients (93%). Conclusions A novel simplified antrum RHB-PVI appears to be a feasible technique for the treatment of paroxysmal atrial fibrillation.

Carbon nanomaterials are used as an electrode of electric double layer capacitors (EDLCs). In this research, we used arc black (AcB) and carbon nanoballoon (CNB) as the electrode material. AcB was produced by an arc discharge of graphite in N 2 atmosphere, and CNB was formed by a heat treatment of AcB. CNB is graphitic, and the particle shape is hollow. CNB has a higher specific capacitance than AcB at a high scan rate. In order to increase the specific capacitance of EDLC, CNB was oxidized at 625 °C in the air. By oxidization, the outer shell of CNB forms wrinkle. We call this material oxidized CNB (Ox-CNB). AcB, CNB, and Ox-CNB were used for the EDLC electrodes and were compared with commercially available activated carbon (AC). Cyclic voltammetry and electrochemical impedance spectroscopy of the EDLC electrodes were measured by an electrochemical measurement system. The specific capacitance of Ox-CNB (29 F/g) was larger than that of AC (16 F/g) at a scan rate of 500 mV/s. Furthermore, Ox-CNB had a high conductivity as a result of impedance measurement. Ox-CNB is an excellent electrode material of EDLC when using at a high charge/discharge rate.

Although a previous randomized study showed that the use of atrial natriuretic peptide (carperitide) improved the long-term prognosis of patients with heart failure, its effect on short-term prognosis remains unclear. We retrospectively identified patients who were admitted to our tertiary-care center with acute decompensated heart failure (ADHF) between April 2009 and December 2013.We divided the eligible patients into two groups: patients who started receiving carperitide on the day of admission (carperitide group) and those who did not receive carperitide during hospitalization (control group). We compared the in-hospital mortality between the two groups using propensity scores derived from 40 baseline variables. We identified 879 eligible patients (mean age, 75.2 years; male, 56.7%), including 336 (38.2%) in the carperitide group and 543 (61.8%) in the control group. One-to-one propensity score matching created 177 pairs. Although the unmatched analysis found a significantly lower in-hospital mortality in the carperitide group than in the control group (3.3% vs. 7.9%, respectively, p = 0.005), the propensity score-matched analysis found no significant difference in in-hospital mortality between the two groups [4.0% vs. 5.1%, p = 0.609; risk difference, −1.1%, 95% confidence interval (CI), −5.5–3.2%]. Logistic regression analysis with adjustment for propensity scores also found no significant association between carperitide use and in-hospital mortality (adjusted odds ratio, 0.61; 95% CI, 0.29 to 1.28; p = 0.605). The present retrospective study showed that carperitide use as the initial treatment was not significantly associated with lower in-hospital mortality in patients with ADHF.

We propose a new method that emulates the expressive appearance of paintbrush strokes on paper. In our system, brush footprint characteristics are modeled using Hidden Markov Models (HMMs). Once the model is trained by a data set of given strokes, it estimates the most likely sequence of footprints for a given input line. The main difference between our method and other ones that use direct texture mapping lies in the estimation of the dynamic behavior of the footprints with respect to input lines. Since our method models simultaneously the physical characteristics of the brush and the drawing styles, it transforms input lines to aesthetic strokes which are really close to true ones, made with a real brush on a paper.

When carbon nanocoils (CNCs) are used in fuel cell electrodes, the diffusion of fuel and gas, and the removal of reaction products, becomes considerably smoother. In this paper, we used CNC as an anode or cathode catalyst support material in direct methanol fuel cells (DMFCs). Other carbon nanoparticles, Arc-Black (AcB) and Vulcan, were also used as catalyst supports to compare with the CNCs. Catalysts were loaded onto nanocarbon materials using the polyol method. We measured the methanol oxidation current of PtRu catalysts loaded on the carbon nanomaterials and the catalyst on CNC showed the highest current. Compared with the catalyst layers of AcB and Vulcan, the catalyst layer of CNCs was confirmed to have several voids. As for the cathode catalysts, the power density of Pt/CNC was 1.2 times higher than that of Pt/Vulcan and 1.6 times higher than that of Pt/AcB.

Carbon nanomaterials with different structures were mixed for an electric double layer capacitor (EDLC) electrode. We used two kinds of carbon nanomaterial: arc black (AcB) and a carbon nanoballoon (CNB). Arc black was synthesized by arc discharge. CNB was produced by heating the prepared AcB at 2400 °C. AcB mostly consists of an amorphous component and has a large specific surface area. On the other hand, CNB has a graphitic surface and a high conductivity. To utilize their characteristics, AcB and CNB were used as the main materials of the EDLC electrode in weight ratios of 1:1, 2:1, and 1:2. The obtained EDLC electrode was filled with 1 M H2SO4 as the electrolyte. As a result, by mixing AcB and CNB, both the power and energy densities became higher than those of AcB or CNB alone. The EDLC mixed in 1:1 weight ratio of AcB and CNB showed the highest performance, with a higher electric power density than activated carbon (AC).