147 research outputs found

    Nucleolar integrity during interphase supports faithful Cdk1 activation and mitotic entry

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    The nucleolus is a dynamic nuclear body that has been demonstrated to disassemble at the onset of mitosis; the relationship between cell cycle progression and nucleolar integrity, however, remains poorly understood. We studied the role of nucleolar proteins in mitosis by performing a global analysis using small interfering RNAs specific to nucleolar proteins; we focused on nucleolar protein 11 (NOL11), with currently unknown mitotic functions. Depletion of NOL11 delayed entry into the mitotic phase owing to increased inhibitory phosphorylation of cyclin-dependent kinase 1 (Cdk1) and aberrant accumulation of Wee1, a kinase that phosphorylates and inhibits Cdk1. In addition to effects on overall mitotic phenotypes, NOL11 depletion reduced ribosomal RNA (rRNA) levels and caused nucleolar disruption during interphase. Notably, mitotic phenotypes found in NOL11-depleted cells were recapitulated when nucleolar disruption was induced by depletion of rRNA transcription factors or treatment with actinomycin D. Furthermore, delayed entry into the mitotic phase, caused by the depletion of pre-rRNA transcription factors, was attributable to nucleolar disruption rather than to G2/M checkpoint activation or reduced protein synthesis. Our findings therefore suggest that maintenance of nucleolar integrity during interphase is essential for proper cell cycle progression to mitosis via the regulation of Wee1 and Cdk1

    Protective Effect of Eicosapentaenoic Acid on Insulin Resistance in Hyperlipidemic Patients and on the Postoperative Course of Cardiac Surgery Patients: The Possible Involvement of Adiponectin

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    Accumulated studies have shown that ω-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have protective roles against inflammatory responses such as hyperlipidemia, diabetes mellitus (DM) and cardiovascular diseases. Here we examined the effects of administering EPA to hyperlipidemic patients and other patients undergoing cardiac surgery to determine whether this treatment would increase plasma EPA levels and to clarify the association between EPA treatment and adiponectin production in hyperlipidemic patients. We also assessed the effect of preoperative EPA administration on postoperative adverse events such as postoperative atrial fibrillation (POAF) and postoperative infection in the cardiac surgery patients. The EPA administration significantly increased the serum EPA concentrations in both patient populations (p<0.001). In the hyperlipidemic patients, the EPA administration significantly increased plasma adiponectin levels (p<0.05), accompanied by a decrease in insulin resistance designated by the HOMA-IR (homeostasis model assessment of insulin resistance) score (p<0.05) and Hs-CRP (high sensitivity C-reactive protein) value (p<0.05). In the cardiac surgery patients, no significant effect of EPA on cardiac adverse events such as POAF was observed. However, our results clearly demonstrated that both the neutrophil-to-lymphocyte ratio and the 2nd-line antibiotic requirement in the EPA group were significantly decreased compared to the untreated control group (p<0.05). We suggest that EPA administration may exert anti-inflammatory effects in patients with hyperlipidemia and in those undergoing cardiac surgery, possibly through an increase in plasma adiponectin levels

    Effect of a two-year health program on brain function, physical fitness and blood chemistry

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    Background: Protocols for carrying out health programs for aged adults have not been clearly presented. Thus, the aim of this study is to examine the effects from the first year to the second year of the Matsumoto health promotion program and to make use of the results in future health promotion for elderly people.Method: The city of Matsumoto offered local residents a two-year health program which includethe use of a pedometer, anthropometry, blood pressure, go/no-go brain function, a physical fitness test and a blood chemistry test. Eighty-six elderly people age 65.9 ± 5.9 years participated in the program. All the participants were given pedometers and a target of 7,000 to 8,000 steps per day was set based on the weight-bearing index. During the first year, the participants did their walking exercise and attended a series of monthly seminars. Then the second year, the participants continued their walking exercise, attended series of monthly seminars and began a 2 hour weight training once a week.Result: The result from the pedometer in the first year showed that the average daily walking step was 6552.9 ± 474.2. The second year, the average daily walking steps was 7170.4 ± 547.9. The results from first year to second year showed significant improvement; the number of incorrect response in the go/no-go tasks (before: 5.3 times ± 0.4, after: 2.9 times ± 0.2, pConclusion: These results from the two-year program suggests that the increase in walking and the 2 hour weight training may reflect the influence of wearing a pedometer, and improved anthropometry, blood pressure, brain function, physical fitness and blood chemistry. However, the girth of the abdomen, handgrip strength and blood chemistry did not show significant improvement. Thus we must think about enlightenment program that wouldinclude muscular strength training and nutrition.ArticleJournal of Community Medicine & Health Education.5(3):349(2015)journal articl

    Difference between two Japanese health promotion programes on measures of health and wellness

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    We implemented and compared two 10-month health education programs in Minowa town and Matsumoto city, Nagano prefecture, Japan. The Matsumoto city cohort underwent a program of monthly classroom activities (CA group), whereas the Minowa town cohort were not only subjected to classroom activities but also performed 90-min strength and weight training once a week and were termed the classroom/training (CT) group. We measured anthropometric, blood pressure, physical fitness, blood chemistry, and brain function variables. All participants were provided pedometers and were encouraged to walk. Monthly seminars included education regarding yoga, exercise, blood pressure, nutrition, and other health-related topics. In total, 92 healthy participants were included in the CA group [age, 66.5 ± 5.4 years (mean ± standard error of mean); 30 males and 62 females] and 46 healthy participants were included in the CT group (mean age 62.7 ± 4.7 years; 22 males and 24 females). We observed significant differences between the average number of steps walked in the CA (7241.7 ± 113.6) and CT (8686.7 ± 167.2) groups. Both the groups both showed significant improvements in anthropometric, blood pressure, physical fitness, blood chemistry, and brain function tests; however, the CT group showed markedly greater improvement after the health education program than before participation. In conclusion, the CT program had added benefits over the CA program because of the higher average amount of walking (approximately 1,400 steps) and the inclusion of a weekly weight-training activity.ArticleINNOVATIVE JOURNAL OF MEDICAL AND HEALTH SCIENCE.5(4):170-181(2015)journal articl

    P2Y12 inhibitor monotherapy after complex percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials

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    Sotomi Y., Matsuoka Y., Hikoso S., et al. P2Y12 inhibitor monotherapy after complex percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials. Scientific Reports 13, 12608 (2023); https://doi.org/10.1038/s41598-023-39213-3.It remains unknown whether the recent trend of short dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy can simply be applied to patients undergoing complex percutaneous coronary intervention (PCI). We performed a systematic review and meta-analysis to evaluate P2Y12 inhibitor monotherapy vs. conventional DAPT in patients undergoing complex PCI and non-complex PCI (PROSPERO: CRD42022335723). Primary endpoint was the 1-year Net Adverse Clinical Event (NACE). Among 5,323 screened studies, six randomized trials fulfilled the eligibility criteria. A total of 10,588 complex PCI patients (5,269 vs. 5,319 patients) and 25,618 non-complex PCI patients (12,820 vs 12,798 patients) were randomly assigned to P2Y12 inhibitor monotherapy vs. conventional DAPT. In complex PCI patients, P2Y12 inhibitor monotherapy was associated with a lower risk of NACE than conventional DAPT [Odds ratio (OR) 0.76, 95% confidence interval (CI) 0.63–0.91, P = 0.003], whereas in non-complex PCI patients, P2Y12 inhibitor monotherapy was associated with a trend toward lowering the risk of NACE (OR 0.86, 95% CI 0.72–1.02, P = 0.09). This meta-analysis across randomized trials demonstrated that a strategy of short DAPT followed by P2Y12 inhibitor monotherapy reduces the risk of 1-year NACE in patients undergoing complex PCI

    Extensive ablation for persistent atrial fibrillation patients with mitral regurgitation: Insights from the EARNEST-PVI prospective randomized trial

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    Sunaga A., Matsuoka Y., Nakatani D., et al. Extensive ablation for persistent atrial fibrillation patients with mitral regurgitation: Insights from the EARNEST-PVI prospective randomized trial. International Journal of Cardiology 410, 132231 (2024); https://doi.org/10.1016/j.ijcard.2024.132231.Background: Extensive ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not yielded consistent results, indicating diversity in their efficacy. Mitral regurgitation (MR) associated with AF may indicate a higher prevalence of arrhythmogenic substrate, suggesting potential benefits of extensive ablation for these patients. Methods: This post-hoc analysis of the EARNEST-PVI trial compared PVI alone versus an extensive ablation strategy (PVI-plus) in persistent AF patients, stratified by MR presence. The primary endpoint of the study was the recurrence of AF. The secondary endpoints included death, cerebral infarction, and procedure-related complications. Results: The trial included 495 eligible patients divided into MR and non-MR groups. The MR group consisted of 192 patients (89 in the PVI-alone arm and 103 in the PVI-plus arm), while the non-MR group had 303 patients (158 in the PVI-alone arm and 145 in the PVI-plus arm). In the non-MR group, recurrence rates were similar between PVI-alone and PVI-plus arms (Log-rank P = 0.47, Hazard ratio = 0.85 [95%CI: 0.54–1.33], P = 0.472). However, in the MR group, PVI-plus was significantly more effective in preventing AF recurrence (Log-rank P = 0.0014, Hazard ratio = 0.40 [95%CI: 0.22–0.72], P = 0.0021). No significant differences were observed in secondary endpoints between the two arms. Conclusions: For persistent AF patients with mild or greater MR, receiving PVI-plus was superior to PVI-alone in preventing AF recurrence. Conversely, for patients without MR, the effectiveness of extensive ablation was not demonstrated. These findings suggest tailoring ablation strategies based on MR presence can lead to better outcomes in AF management

    Calreticulin and integrin alpha dissociation induces anti-inflammatory programming in animal models of inflammatory bowel disease

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    Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils. Transcriptome analysis on colon samples from dextran sodium sulfate-induced colitis mice reveals that the increased expression of pro-inflammatory genes is downregulated by ER-464195-01. Its prophylactic and therapeutic administration to IBD mouse models ameliorates the severity of their diseases. We propose that leukocytes infiltration via the binding of CRT to ITGAs is necessary for the onset and development of the colitis and the inhibition of this interaction may be a novel therapeutic strategy for the treatment of IBD
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