CpG oligodeoxynucleotides induce strong up-regulation of interleukin 33 via Toll-like receptor 9

We previously reported the strong immunostimulatory effects of a CpG oligodeoxynucleotide (ODN), designated MsST, from the lacZ gene of Streptococcus (S.) thermophilus ATCC19258. Here we show that 24 h of stimulation with MsST in mouse splenocytes and peritoneal macrophages strongly induces expression of interleukin (IL)-33, a cytokine in the IL-1 superfamily. Other IL-1 superfamily members, including IL-1 alpha, IL-1 beta and IL-18, are down-regulated after 24 h of stimulation of MsST. We also found that MsST-induced IL-33 mRNA expression is inhibited by the suppressive ODN A151, which can inhibit Toll-like receptor 9 (TLR9)-mediated responses. This is the first report to show that IL-33 can be induced by CpG ODNs. The strong induction of IL-33 by MsST suggests that it may be a potential therapeutic ODN for the treatment of inflammatory disease. The presence of a strong CpG ODN in S. thermophilus also suggests that the bacterium may be a good candidate as a starter culture for the development of new physiologically functional foods.ArticleBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 394(1):81-86 (2010)journal articl

First-principles study of electron transport through C20C_{20} cages

Electron transport properties of C$_{20}$ molecules suspended between gold electrodes are investigated using first-principles calculations. Our study reveals that the conductances are quite sensitive to the number of C$_{20}$ molecules between electrodes: the conductances of C$_{20}$ monomers are near 1 G$_{0}$, while those of dimers are markedly smaller, since incident electrons easily pass the C$_{20}$ molecules and are predominantly scattered at the C$_{20}$-C$_{20}$ junctions. Moreover, we find both channel currents locally circulating the outermost carbon atoms.Comment: 8 pages and 3 figure

Sedentary Time and All-Cause Mortality

BACKGROUND: This study aimed to determine the association between sedentary time and mortality with regard to leisure‐time physical activity with or without cardiometabolic diseases such as hypertension, dyslipidemia, and diabetes mellitus. METHODS AND RESULTS: Using data from the J‐MICC (Japan Multi‐Institutional Collaborative Cohort) Study, 64 456 participants (29 022 men, 35 434 women) were analyzed. Hazard ratios (HRs) and 95% CIs were used to characterize the relative risk of all‐cause mortality to evaluate its association with sedentary time (categorical variables: <5, 5 to <7, 7 to <9, ≥9 h/d and 2‐hour increments in exposure) according to the self‐reported hypertension, dyslipidemia, and diabetes mellitus using a Cox proportional hazards model. A total of 2257 participants died during 7.7 years of follow‐up. The corresponding HRs for each 2‐hour increment in sedentary time among participants with all factors, no factors, hypertension, dyslipidemia, and diabetes mellitus were 1.153 (95% CI, 1.114–1.194), 1.125 (95% CI, 1.074–1.179), 1.202 (95% CI, 1.129–1.279), 1.176 (95% CI, 1.087–1.273), and 1.272 (95% CI, 1.159–1.396), respectively. Furthermore, when analyzed according to the combined different factors (hypertension, dyslipidemia, and diabetes mellitus), HRs increased with each additional factor, and participants reporting all 3 conditions had the highest HR of 1.417 (95% CI, 1.162–1.728) independently of leisure‐time metabolic equivalents. CONCLUSIONS: The association between sedentary time and increased mortality is stronger among patients with hypertension, dyslipidemia, and diabetes mellitus regardless of leisure‐time physical activity in a large Japanese population

Seven-plus hours of daily sedentary time and the subsequent risk of breast cancer : Japan Multi-Institutional Collaborative Cohort Study

This study aimed to investigate the association between daily sedentary time and the risk of breast cancer (BC) in a large Japanese population. The participants were 36,023 women aged 35–69 years from the Japan Multi-Institutional Collaborative Cohort Study. Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for BC incidence in relation to time spent sedentarily (categorical variables: <7 and ≥7 hours/day [h/d]). Additionally, the associations of BC incidence to the joint effect of sedentary time with each component of physical activity, such as leisure-time metabolic equivalents (METs), frequency of leisure-time physical activity, and daily walking time, were examined. During 315,189 person-years of follow-up, 554 incident cases of BC were identified. When compared to participants who spent <7 h/d sedentary, those who spent ≥7 h/d sedentary have a significantly higher risk of BC (HR, 1.36; 95% CI, 1.07–1.71). The corresponding HRs among participants who spent ≥7 h/d sedentary with more physical activity, such as ≥1 h/d for leisure-time METs, ≥3 days/week of leisure-time physical activity, and ≥1 h/d of daily walking were 1.58 (95% CI, 1.11–2.25), 1.77 (95% CI, 1.20–2.61), and 1.42 (95% CI, 1.10–1.83), respectively, compared with those who spent <7 h/d sedentary. This study found that spending ≥7 h/d of sedentary time is associated with the risk of BC. Neither leisure-time physical activity nor walking had a BC-preventive effect in those with ≥7 h/d of sedentary time

Smoking, Drinking, and Genetic Factors Affect HDL-cholesterol

Background: Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross- sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. Methods: Data from 11,498 men and women aged 35–69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P <5 × 10−8) were selected from the GWAS catalog, of which seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). Results: We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex, and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. Conclusion: The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking

Long-term outcomes of lung transplantation requiring renal replacement therapy: A single-center experience

Background Life-long immunosuppressive therapy after lung transplantation (LT) may lead to end-stage renal disease (ESRD), requiring renal replacement therapy (RRT). We aimed to investigate the characteristics and long-term outcomes of patients undergoing LT and requiring RRT. Methods This study was a single-center, retrospective cohort study. The patients were divided into the RRT (n = 15) and non-RRT (n = 170) groups. We summarized the clinical features of patients in the RRT group and compared patient characteristics, overall survival, and chronic lung allograft dysfunction (CLAD)-free survival between the two groups. Results The cumulative incidences of ESRD requiring RRT after LT at 5, 10, and 15 years were 0.8 %, 7.6 %, and 25.2 %, respectively. In the RRT group, all 15 patients underwent hemodialysis but not peritoneal dialysis, and two patients underwent living-donor kidney transplantation. The median follow-up period was longer in the RRT group than in the non-RRT group (P Conclusions Favorable long-term outcomes can be achieved by RRT for ESRD after LT