Background:Stent edge-related restenosis (SER) remains a potential limitation of drug-eluting stent (DES). Hinge motion at the stent edge could lead to mechanical stress and contribute to incidents ...of SER. We investigated the effect of hinge motion on SER after implantation of current-generation DES in the right coronary artery (RCA), where excessive vessel movement is commonly observed.Methods and Results:Of 647 consecutive lesions in the RCA treated with second-generation or later DESs, 426 with follow-up angiography were included in this study. Intravascular imaging analysis was performed for 584 stent edges and reference segments. Binary restenosis occurred in 42 lesions (9.9%), and 55% were SERs. The hinge angle was significantly larger in the SER group than in the other restenosis or the no-restenosis group (17.9° vs. 11.6° and 10.6°, respectively; P<0.001). Lesions with an excessive hinge angle (>11.5°) had an increased rate of target lesion revascularization (19.1% vs. 7.2%; P<0.001) during the median follow-up period of 1,578 days. In per-edge analysis, hinge angle and residual plaque burden were independent predictors of SER. The coexistence of excessive hinge motion and residual plaque burden had a synergistic effect on stenotic progression in quantitative angiographic analysis (Pinteraction<0.001) at follow-up angiography.Conclusions:Substantial stress determined by angulation at a stent edge and its interaction with residual plaque can be considered as one plausible mechanism for SER.
Although myocarditis following immune checkpoint inhibitor (ICI) therapy is rarely reported, it is considered clinically important because of its high mortality rate. Although various tests may be ...used for early diagnosis, abnormalities suggestive of myocarditis may not be detected. We report a case of ICI-induced myositis and concurrent asymptomatic myocarditis with mild cardiac marker elevation following nivolumab therapy in a 79-year-old man with metastatic gastric cancer. In this case, cardiac magnetic resonance imaging was useful for diagnosis. Treatment with oral prednisolone rapidly improved the patient's symptoms and creatine kinase levels. Follow-up examination revealed no flare-up of myositis and exacerbation of myocarditis. Since ICI-induced myositis is often complicated by myocarditis, this case report highlights the importance of detecting concurrent myocarditis in patients with ICI-induced myositis through intensive cardiac assessments to improve clinical outcomes.
Fucoidan is an active component of seaweed that has been shown to inhibit proliferation and induce apoptotic cell death in several tumor cells. However, the detailed mechanisms underlying this ...process have not yet been elucidated. In the present report, we investigated the effect of fucoidan on the induction of apoptosis in human breast cancer MCF-7 cells. Our data demonstrated that fucoidan reduced the viable cell number of MCF-7 cells in a dose- and time-dependent manner. In contrast, fucoidan did not affect the viable cell number of normal human mammary epithelial cells. Results from the apoptosis assay demonstrated that fucoidan induced internucleosomal DNA fragmentation, chromatin condensation, activation of caspase-7, -8, and -9, and cleavage of poly(ADP ribose) polymerase. Furthermore, expression of Bid was decreased, whereas truncated Bid was increased by fucoidan treatment. There was also a decline in cytosolic Bax and a striking increase of cytosolic cytochrome c. Caspase-8-specific inhibitor, z-ITED-fmk, canceled the cytotoxicity of fucoidan, activation of caspase-7, -8, and -9, and a series of changes in Bax, Bid, and cytochrome c. However, caspase-9-specific inhibitor exerted a moderate inhibitory effect on the cytotoxicity of fucoidan. These data indicated that fucoidan could induce apoptotic cell death through a caspase-8-dependent pathway in MCF-7 cells.
Prevention of postprandial hypertriglyceridemia is an important consideration for reducing the risk of developing cardiovascular disease. While blueberry fruits have been reported to ameliorate lipid ...metabolism in humans, there are only few research reports on the effects of blueberry leaves (BL). Here, we investigated the efficacy of BL on postprandial hyperlipidemia in subjects with high fasting triacylglycerol (TG) concentrations. Randomized, double-blind, cross-over design study was conducted. The subjects consumed a BL containing beverage or a placebo beverage before a fat-enriched test meal. Blood samples were collected prior to and 1, 2, 3, 4, and 5 hours after consuming the test beverage. The postprandial serum TG and remnant-like particle cholesterol (RLP-C) concentrations were significantly lower in the BL beverage compared with those in the placebo beverage. Additionally, BL was more effective in subjects with high fasting ghrelin with gastric emptying function. In current study, fasting ghrelin correlated with the increase in postprandial serum TG, suggesting that BL ameliorates hypertriglyceridemia through delayed gastric emptying. In conclusion, this pilot study suggests that BL may be useful as an early dietary therapy for treating postprandial hyperlipidemia.
The aim of this study was to evaluate the involvement of nanoparticles prepared from Allium cepa L. as anti-inflammatory agents. In the present study, we identified nanoparticles from Allium cepa L. ...using the ultracentrifugation exosome purification method. The nanoparticles were referred to as 17,000× g and 200,000× g precipitates, and they contained quercetins, proteins, lipids, and small-sized RNA. The nanoparticles inhibited nitric oxide production from lipopolysaccharide (LPS)-stimulated RAW264 cells without cytotoxic properties. Cellular incorporation was confirmed by laser microscopic observation after PKH26 staining. The inhibition of caveolae-dependent endocytosis and macropinocytosis significantly prevented the incorporation of the nanoparticles but had no effect on the inhibition of nitric oxide in RAW264 cells. Collectively, the identified nanoparticles were capable of inhibiting the LPS response via extracellular mechanisms. Taken together, the way of consuming Allium cepa L. without collapsing the nanoparticles is expected to provide an efficient anti-inflammatory effect.
The generalization of deep neural network algorithms to a broader population is an important challenge in the medical field. We aimed to apply self-supervised learning using masked autoencoders ...(MAEs) to improve the performance of the 12-lead electrocardiography (ECG) analysis model using limited ECG data. We pretrained Vision Transformer (ViT) models by reconstructing the masked ECG data with MAE. We fine-tuned this MAE-based ECG pretrained model on ECG-echocardiography data from The University of Tokyo Hospital (UTokyo) for the detection of left ventricular systolic dysfunction (LVSD), and then evaluated it using multi-center external validation data from seven institutions, employing the area under the receiver operating characteristic curve (AUROC) for assessment. We included 38,245 ECG-echocardiography pairs from UTokyo and 229,439 pairs from all institutions. The performances of MAE-based ECG models pretrained using ECG data from UTokyo were significantly higher than that of other Deep Neural Network models across all external validation cohorts (AUROC, 0.913-0.962 for LVSD, p < 0.001). Moreover, we also found improvements for the MAE-based ECG analysis model depending on the model capacity and the amount of training data. Additionally, the MAE-based ECG analysis model maintained high performance even on the ECG benchmark dataset (PTB-XL). Our proposed method developed high performance MAE-based ECG analysis models using limited ECG data.
Limited data exists on ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) managed by a well-organized cardiac care network in a metropolitan area. We analyzed the Tokyo CCU ...network database in 2009–2010. Of 4329 acute myocardial infarction (AMI) patients including STEMI (
n
= 3202) and NSTEMI (
n
= 1127), percutaneous coronary intervention (PCI) was performed in 88.8 % of STEMI and 70.4 % of NSTEMI patients. Mean onset-to-door and door-to-balloon times in STEMI patients were shorter than those in NSTEMI patients (167 vs 233 and 60 vs 145 min, respectively,
p
< 0.001). Coronary artery bypass graft surgery was performed in 4.2 % of STEMI and 11.4 % of NSTEMI patients. In-hospital mortality was significantly higher in STEMI patients than NSTEMI patients (7.7 vs 5.1 %,
p
< 0.007). Independent correlates of in-hospital mortality were advanced age, low blood pressure, and high Killip classification, statin-treated dyslipidemia and PCI within 24 h were favorable predictors for STEMI. High Killip classification, high heart rate, and hemodialysis were significant predictors of in-hospital mortality, whereas statin-treated dyslipidemia was the only favorable predictor for NSTEMI. In conclusion, patients with MI received PCI frequently (83.5 %) and promptly (door-to-balloon time; 66 min), and had favorable in-hospital prognosis (in-hospital mortality; 7.0 %). In addition to traditional predictors of in-hospital death, statin-treated dyslipidemia was a favorable predictor of in-hospital mortality for STEMI and NSTEMI patients, whereas hemodialysis was the strongest predictor for NSTEMI patients.
White adipose tissue expands rapidly due to increased adipocyte number (hyperplasia) and size (hypertrophy), which results in obesity. Adipogenesis is a process of the formation of mature adipocytes ...from precursor cells. Additionally, obesity-related metabolic complications, such as fatty liver and insulin resistance, are linked to adipogenesis. On the contrary, autophagy is a catabolic process; essential to maintain cellular homeostasis via the degradation or recycling of unnecessary or damaged components. Importantly, autophagy dictates obesity and adipogenesis. Hence, a clear understanding of how autophagy regulates adipogenesis is crucial for drug development and the prevention and treatment of obesity and its associated disorders, such as type 2 diabetes, cardiovascular disease, and cancer. In this review, we highlighted recent findings regarding the crosstalk between adipogenesis and autophagy, as well as the molecules involved. Furthermore, the review discussed how bioactive compounds regulate adipogenesis by manipulating autophagy and underlying molecular mechanisms. Based on in vitro and animal studies, we summarized the effects of bioactive compounds on adipogenesis and autophagy. Hence, human studies are necessary to validate the effectiveness and optimal dosage of these bioactive compounds.
The water-solubility of coenzyme Q10 (CoQ10) is extremely low because of its hydrophobicity, which results in low bioavailability. In this study, peptide mixtures derived from different proteins ...(casein, albumin, gelatin, lysozyme, zein and hemoglobin) were prepared and used as dispersants ofCoQ10. Most peptide mixtures, except for that derived from lysozyme, enhanced the water-dispersibility of CoQ10 by forming complexes with CoQ10. In particular, the apparent solubility of CoQ10complexed with the casein hydrolysate (Pepcas) was the highest. Pepcas was fractionated by ammonium sulfate precipitation and ultrafiltration to find the most effective peptides for enhancing water-dispersibility of CoQ10. The peptide fraction that had a relatively hydrophobic nature and peptides of higher-than-average molecular weights (PepcasA) was found to be the most effective. Results from differential thermal analysis and powder X-ray diffraction revealed that the complex between CoQ10 and PepcasA in the solid state was amorphous. In solution, the complex is a hydrocolloid with particle sizes of 154–279 nm.
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Background: Left heart abnormalities are risk factors for heart failure. However, echocardiography is not always available. Electrocardiograms (ECGs), which are now available from wearable devices, ...have the potential to detect these abnormalities. Nevertheless, whether a model can detect left heart abnormalities from single Lead I ECG data remains unclear.Methods and Results: We developed Lead I ECG models to detect low ejection fraction (EF), wall motion abnormality, left ventricular hypertrophy (LVH), left ventricular dilatation, and left atrial dilatation. We used a dataset comprising 229,439 paired sets of ECG and echocardiography data from 8 facilities, and validated the model using external verification with data from 2 facilities. The area under the receiver operating characteristic curves of our model was 0.913 for low EF, 0.832 for wall motion abnormality, 0.797 for LVH, 0.838 for left ventricular dilatation, and 0.802 for left atrial dilatation. In interpretation tests with 12 cardiologists, the accuracy of the model was 78.3% for low EF and 68.3% for LVH. Compared with cardiologists who read the 12-lead ECGs, the model’s performance was superior for LVH and similar for low EF.Conclusions: From a multicenter study dataset, we developed models to predict left heart abnormalities using Lead I on the ECG. The Lead I ECG models show superior or equivalent performance to cardiologists using 12-lead ECGs.
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