受賞区分：国際学会・会議・シンポジウム等の賞 

受賞区分：国際学会・会議・シンポジウム等の賞 

記述言語：英語   出版者・発行元：Pharmacology Research and Perspectives  

Dyslipidemia, characterized by abnormal serum cholesterol or triglyceride (TG) concentrations, is prevalent among middle-aged and older adults and contributes to atherosclerosis and increased cardiovascular risk. Although oral statins effectively decrease low-density lipoprotein cholesterol, patients with high-TG concentrations remain at significant risk for atherosclerotic cardiovascular disease. Weibull analysis, a statistical method widely applied in reliability engineering and medicine, is suitable for assessing arterial stiffness, which reflects vascular aging or deterioration. This study explored the relationship between TG concentrations and arterial stiffness via Weibull analysis in patients treated with statins (STG) and patients without statin treatment (No-STG). The mode of the Weibull distribution was greater for STG (97.8 mg/dL) than for No-STG (80.7 mg/dL). Notably, compared with No-STG patients, STG patients presented lower hazard functions for TG concentrations up to 170 mg/dL. However, above 170 mg/dL, the hazard function for STG was equal to or slightly greater than that for No-STG. These findings suggest that without statin therapy, atherosclerosis may develop at lower TG concentrations, whereas statins effectively delay its onset. However, the data also highlight the limitations of statins in significantly reducing TG concentrations. This information underscores the importance of patient education in preventing the progression of atherosclerosis. Encouraging lifestyle changes, including improved exercise and dietary habits, can complement statin therapy to optimize cardiovascular health. These findings provide a basis for promoting patient awareness and fostering the proactive management of cardiovascular risk factors.

DOI： 10.1002/prp2.70159

Open Access

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：Clinical Nutrition  

Background and aims: Soybeans and their ingredients have antioxidant and anti-inflammatory effects on cardiovascular diseases. β-Conglycinin (β-CG), a major constituent of soy proteins, is protective against obesity, hypertension, and chronic kidney disease, but its effects on heart failure remain to be elucidated. We tested the effects of β-CG on left ventricular (LV) remodeling in pressure overload-induced heart failure. Methods: A transverse aortic constriction (TAC)-induced pressure overload was applied to the heart in 7-week-old C57BL6 male mice that were treated with β-CG, GlcNAc, or sodium propionate. Gut microbiota was analyzed by 16S rRNA sequencing. Fecal short-chain fatty acids (SCFAs) were quantified by GC-MS. The effects of oral antibiotics were examined in β-CG-fed mice. Results: β-CG ameliorated impaired cardiac contractions, cardiac hypertrophy, and myocardial fibrosis in TAC-operated mice. As β-CG is a highly glycosylated protein, we examined the effects of GlcNAc. GlcNAc had similar but less efficient effects on LV remodeling compared to β-CG. β-CG increased three major SCFA-producing intestinal bacteria, as well as fecal concentrations of SCFAs, in sham- and TAC-operated mice. Oral administration of antibiotics nullified the effects of β-CG in TAC-operated mice by markedly reducing SCFA-producing intestinal bacteria and fecal SCFAs. In contrast, oral administration of sodium propionate, one of SCFAs, ameliorated LV remodeling in TAC-operated mice to a similar extent as β-CG. Conclusions: β-CG was protective against TAC-induced LV remodeling, which was likely to be mediated by increased SCFA-producing gut microbiota and increased intestinal SCFAs. Modified β-CG and/or derivatives arising from β-CG are expected to be developed as prophylactic and/or therapeutic agents to ameliorate devastating symptoms in heart failure.

DOI： 10.1016/j.clnu.2024.09.045

Open Access

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：Scientific Reports  

Titin, a giant sarcomeric protein, regulates diastolic left ventricular (LV) passive stiffness as a molecular spring and could be a therapeutic target for diastolic dysfunction. Sacubitril/valsartan (Sac/Val), an angiotensin receptor neprilysin inhibitor, has been shown to benefit patients with heart failure with preserved ejection fraction. The effect of Sac/Val is thought to be due to the enhancement of the cGMP/PKG pathway via natriuretic peptide. In this study, the effects of Sac/Val on LV diastolic dysfunction are demonstrated in a mouse diabetic cardiomyopathy model focusing on titin phosphorylation. Sac/Val-treated diabetic mice showed a greater increase in myocardial levels of cGMP-PKG than Val-treated and control mice. Conductance catheter analysis showed a significant reduction in LV stiffness in diabetic mice, but not in non-diabetic mice. Notably, diastolic LV stiffness was significantly reduced in Sac/Val-treated diabetic hearts compared with Val-treated or vehicle-treated diabetic mice. The phosphorylation level of titin (N2B), which determines passive stiffness and modulates active contraction, was higher in Sac/Val-treated hearts compared with Val-treated hearts in diabetic mice. Given that alteration of titin phosphorylation through PKG contributes to myocardial stiffness, the beneficial effects of Sac/Val in heart failure might be partly attributed to the induction of titin phosphorylation.

DOI： 10.1038/s41598-024-75757-8

Open Access

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PubMed

記述言語：日本語   出版者・発行元：Physiological Reports  

Phosphatidylinositol 3-kinase (PI3K) signaling promotes the differentiation and proliferation of regulatory B (Breg) cells, and the lipid phosphatase phosphatase and tensin homolog deleted on chromosome 10 (PTEN) antagonizes the PI3K–Akt signaling pathway. We previously demonstrated that cardiac Akt activity is increased and that restraint stress exacerbates hypertension and both heart and adipose tissue (AT) inflammation in DS/obese rats, an animal model of metabolic syndrome (MetS). We here examined the effects of restraint stress and pharmacological inhibition of PTEN on heart and AT pathology in such rats. Nine-week-old animals were treated with the PTEN inhibitor bisperoxovanadium-pic [bpV(pic)] or vehicle in the absence or presence of restraint stress for 4 weeks. BpV(pic) treatment had no effect on body weight or fat mass but attenuated hypertension in DS/obese rats subjected to restraint stress. BpV(pic) ameliorated left ventricular (LV) inflammation, fibrosis, and diastolic dysfunction as well as AT inflammation in the stressed rats. Restraint stress reduced myocardial capillary density, and this effect was prevented by bpV(pic). In addition, bpV(pic) increased the proportions of Breg and B-1 cells as well as reduced those of CD8+ T and B-2 cells in AT of stressed rats. Our results indicate that inhibition of PTEN by bpV(pic) alleviated heart and AT inflammation in stressed rats with MetS. These positive effects of bpV(pic) are likely due, at least in part, to a reduction in blood pressure, an increase in myocardial capillary formation, and an altered distribution of immune cells in fat tissue that result from the activation of PI3K–Akt signaling.

DOI： 10.14814/phy2.15165

Open Access

Web of Science

Scopus

PubMed

記述言語：日本語   出版者・発行元：Acta Cytologica  

Introduction: Liquid-based cytology (LBC) is increasingly used for nongynecologic applications. However, the cytological preparation of LBC specimens is influenced by the processing technique and the preservative used. In this study, the influence of the processing techniques and preservatives on cell morphology was examined mathematically and statistically. Methods: Cytological specimens were prepared using the ThinPrep (TP), SurePath (SP), and AutoSmear methods, with 5 different preservative solutions. The cytoplasmic and nuclear areas of Papanicolaou-stained specimens were measured for all samples. Results: The cytoplasmic and nuclear areas were smaller in cells prepared using the 2 LBC methods, compared to that prepared using the AutoSmear method, irrespective of the preservative used. The cytoplasmic and nuclear areas of cells prepared using the SP method were smaller than those of cells prepared using the TP method, irrespective of the preservative used. There were fewer differences among the cytoplasmic areas of cells prepared with different preservative solutions using the TP method; however, the cytoplasmic areas of cells prepared using the SP method changed with the preservative solution used. Conclusions: The most significant difference affecting the cytoplasmic and nuclear areas was the processing technique. The TP method increased the cytoplasmic and nuclear areas, while the methanol-based PreservCyt solution enabled the highest enlargement of the cell. LBC is a superior preparation technique for standardization of the specimens. Our results offer a better understanding of methods suitable for specimen preparation for developing precision AI-based diagnosis in cytology.

DOI： 10.1159/000519335

Web of Science

Scopus

PubMed