👤 Yukari Yamashiro

The mutual effects of different activity intensities in daily life, such as sedentary behavior (SB) and physical activity (PA), on dementia onset are not yet fully understood. The purpose of this study was to examine the association between replacing SB with PA and the risk of dementia in older adults by using the isotemporal substitution (IS) model. Prospective cohort study. Community-dwelling older adults living without dementia in Takahama, were enrolled, interviewed, and physically examined. Follow-up data were collected from the Japanese Public Health Insurance and/or Long-Term Care Insurance system databases during follow-up. SB and PA data [light-intensity PA (LPA) and moderate-to-vigorous PA (MVPA)] were measured using a triaxial accelerometer for 14 days, and the average daily time for SB and PA was calculated in 10-minute increments. Participants were followed up monthly for new-onset dementia over 5 years. Cox proportional-hazards regression analysis was performed by using IS to estimate the effect of replacing one activity with another on the dementia onset. We included 1664 participants (mean ± standard deviation age, 73.1 ± 5.9 years) in this study. Over 5 years, 128 of 1664 participants developed dementia. Replacing 10 min/d of SB with LPA (hazard ratio, 0.86; 95% CI, 0.75-0.99) or MVPA (0.84; 0.74-0.96) was associated with a lower risk of dementia. Replacing 10 minutes of SB with LPA or MVPA was associated with a lower risk of dementia. Feasible behavioral changes in daily life may lead to a healthy life expectancy. Show less

The vertebrate retina is a laminated tissue with a relatively simple structure compared with the brain, and its accessibility makes it an excellent model for studying damage and repair in the central nervous system. This study investigated the regenerative process of the photoreceptor layer in medaka ( Medaka embryos at 3 days post fertilization (dpf) were irradiated with 7-10 Gy to determine the lethal threshold, from which 8 Gy was determined to be a sub-lethal dose. In 8 Gy-irradiated embryos, eye size was assessed by stereomicroscopy and photoreceptor regeneration was histologically evaluated by Zpr1 immunohistochemistry at 8, 14, and 21 dpf. Visual function was evaluated by optomotor response under standard and reduced-contrast conditions. Irradiation at 10 Gy induced severe cone loss, resulting in mortality from 15 dpf. In contrast, larvae exposed to 8 Gy showed no significant alterations in central or dorsal cones compared with controls, whereas ventral cones were significantly shorter and fewer in number. These abnormalities, as well as eye size, gradually recovered to control levels by 21 dpf. Although transient reductions in eye size and ventral cones were observed, OMR testing revealed no impairment of visual performance at 8, 14, or 21 dpf, even under stringent low-contrast conditions. Sub-lethal gamma irradiation transiently induced localized damage especially in the ventral retina and reduction in eye size, both of which were fully repaired within 21 dpf. Behavioral analysis demonstrated that such transient, repairable damage does not impair visual function in irradiated medaka larvae. Show less

Dental pulp stem cells (DPSCs) can differentiate into vascular endothelial cells and display sprouting ability. During this process, DPSC responses to the extracellular microenvironment and cell-extracellular matrix interactions are critical in regulating their ultimate cell fate. Heparan sulfate (HS) glycosaminoglycan, a major component of extracellular matrix, plays important roles in various biological cell activities by interacting with growth factors and relative receptors. However, the regulatory function of HS on vasculogenesis of mesenchymal stem cells remains unclear. The objective of this study was to investigate the role of HS in endothelial differentiation and vasculogenesis of DPSCs. Our results show that an HS antagonist suppressed the proliferation and sprouting ability of DPSCs undergoing endothelial differentiation. Furthermore, expression of proangiogenic markers significantly declined with increasing dosages of the HS antagonist; in contrast, expression of stemness marker increased. Silencing of exostosin 1 (EXT1), a crucial glycosyltransferase for HS biosynthesis, in DPSCs using a short hairpin RNA significantly altered their gene expression profile. In addition, Show less

The aim of this study is to characterize the effects of high-dose radiation therapy (HDRT) on Notch signaling components of the tumor vasculature. Human umbilical vein endothelial cells monolayers were exposed to different single fraction doses of irradiation; ribonucleic acid RNA was isolated and polymerase chain reaction was performed for Notch signaling components. The vascular response to radiation therapy was examined in a xenograft model of neuroblastoma. Tumors were treated with 0 Gy, 2 Gy, and 12 Gy single fraction doses and analyzed by double immunofluorescence staining for Notch1, Notch ligands Jagged1 and Dll4, and the endothelial cell (EC) marker endomucin. To assess the role of Notch in vivo, NGP xenograft tumors expressing Fc or Notch1- In human umbilical vein endothelial cells monolayers doses ≥8 Gy increased expression of NOTCH1, JAG1, and Notch target genes HEY1 and HEY2 as early as 6 hours after irradiation. In vivo, 12 Gy significantly increased Notch1 and Jagged1 in tumor ECs compared with 0 Gy or 2 Gy after 72 hours. Combining HDRT with Notch inhibition using the Notch1- HDRT induced Notch1 expression and increased Notch1 signaling in the endothelial component of tumor vasculature, which was not observed with lower doses. This increase in Notch1 activation might protect tumor vessels from HDRT induced damage and regulate EndMT process. Show less

Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD) more frequently seen in East Asians, has both common and distinct clinical manifestations with typical neovascular AMD (tAMD). We aim to examine the extent to which common genetic variants are shared between these two subtypes. We performed the meta-analysis of association in a total of 1062 PCV patients, 1157 tAMD patients and 5275 controls of East Asian descent from the Genetics of AMD in Asians Consortium at the 34 known AMD loci. A total of eight loci were significantly associated with PCV, including age-related maculopathy susceptibility 2 (ARMS2)-HtrA serine peptidase 1 (HTRA1), complement factor H (CFH), C2-CFB-SKIV2L, CETP, VEGFA, ADAMTS9-AS2 and TGFBR1 (P<5 × 10 Show less