25 research outputs found
Effect of the Newly Introduced Hepatitis B Vaccination Program on Infection Control Measures
Argonaute2 is a potential target for siRNA-based cancer therapy for HT1080 human fibrosarcoma.
Small interfering RNAs (siRNAs) are small RNA
molecules that have a potent, sequence-specific gene
silencing effect and therefore show promise for therapeutic
use as molecular-targeted drugs for the treatment of various
genetic diseases, including cancer. The aim of the present
study was to evaluate whether Argonaute2 (Ago2) is a
therapeutically effective target for siRNA-based cancer
therapy. Ago2 is the key protein in mammalian RNAi and
is also known as the only member of the Ago family that
mediates the microRNA (miRNA)-dependent cleavage of
targeted mRNAs. It is assumed that these unique properties
of the Ago2 protein can play a central role in the regulation
of the miRNA pathway and subsequent translational
inhibition of miRNA-targeted mRNAs, including cell
survival and cancer progression. To assess its therapeutic
effect, siRNA against Ago2 (Ago2-siRNA) was transfected
into HT1080 human fibrosarcoma cells, which are malignant
cancer cells. Ago2 gene silencing resulted in the
inhibition of cell growth and the induction of apoptosis and
G0/G1 arrest in the cell cycle. In addition, Ago2 knockdown
induced morphological changes and actin stress fiber
formation in the cells. The results of a microarray study
showed that Ago2 suppression stimulated several crucial
genes related to apoptosis, the cell cycle, immune response,
cell adhesion, metabolism, etc. Repeated intratumoral
injection of Ago2-siRNA/cationic liposome complex induced
tumor growth suppression in an HT1080 xenograft
model. These results suggest that the suppression of the Ago2 gene may be useful for the inhibition of cancer
progression and that Ago2 may be a desirable target for
siRNA-based cancer therapy
An enzyme-linked immunosorbent assay for measuring GPIHBP1 levels in human plasma or serum
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An enzyme-linked immunosorbent assay for measuring GPIHBP1 levels in human plasma or serum
BackgroundGlycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a glycosylphosphatidylinositol (GPI)-anchored protein of capillary endothelial cells, transports lipoprotein lipase to the capillary lumen and is essential for the lipolytic processing of triglyceride-rich lipoproteins.ObjectiveBecause some GPI-anchored proteins have been detected in plasma, we tested whether GPIHBP1 is present in human blood and whether GPIHBP1 deficiency or a history of cardiovascular disease affected GPIHBP1 circulating levels.MethodsWe developed 2 monoclonal antibodies against GPIHBP1 and used the antibodies to establish a sandwich enzyme-linked immunosorbent assay (ELISA) to measure GPIHBP1 levels in human blood.ResultsThe GPIHBP1 ELISA was linear in the 8 to 500 pg/mL range and allowed the quantification of GPIHBP1 in serum and in pre- and post-heparin plasma (including lipemic samples). GPIHBP1 was undetectable in the plasma of subjects with null mutations in GPIHBP1. Serum GPIHBP1 median levels were 849 pg/mL (range: 740-1014) in healthy volunteers (n = 28) and 1087 pg/mL (range: 877-1371) in patients with a history of cardiovascular or metabolic disease (n = 415). There was an extremely small inverse correlation between GPIHBP1 and triglyceride levels (r = 0.109; P < .0275). GPIHBP1 levels tended to be slightly higher in patients who had a major cardiovascular event after revascularization.ConclusionWe developed an ELISA for quantifying GPIHBP1 in human blood. This assay will be useful to identify patients with GPIHBP1 deficiency and patients with GPIHBP1 autoantibodies. The potential of plasma GPIHBP1 as a biomarker for metabolic or cardiovascular disease is yet questionable but needs additional testing
Restoration of Dioxin-Induced Damage to Fetal Steroidogenesis and Gonadotropin Formation by Maternal Co-Treatment with α-Lipoic Acid
<div><p>2,3,7,8-Tetrachlorodibenzo-<em>p</em>-dioxin (TCDD), an endocrine disruptor, causes reproductive and developmental toxic effects in pups following maternal exposure in a number of animal models. Our previous studies have demonstrated that TCDD imprints sexual immaturity by suppressing the expression of fetal pituitary gonadotropins, the regulators of gonadal steroidogenesis. In the present study, we discovered that all TCDD-produced damage to fetal production of pituitary gonadotropins as well as testicular steroidogenesis can be repaired by co-treating pregnant rats with α-lipoic acid (LA), an obligate co-factor for intermediary metabolism including energy production. While LA also acts as an anti-oxidant, other anti-oxidants; <em>i.e.</em>, ascorbic acid, butylated hydroxyanisole and edaravone, failed to exhibit any beneficial effects. Neither wasting syndrome nor CYP1A1 induction in the fetal brain caused through the activation of aryl hydrocarbon receptor (AhR) could be attenuated by LA. These lines of evidence suggest that oxidative stress makes only a minor contribution to the TCDD-induced disorder of fetal steroidogenesis, and LA has a restorative effect by targeting on mechanism(s) other than AhR activation. Following a metabolomic analysis, it was found that TCDD caused a more marked change in the hypothalamus, a pituitary regulator, than in the pituitary itself. Although the components of the tricarboxylic acid cycle and the ATP content of the fetal hypothalamus were significantly changed by TCDD, all these changes were again rectified by exogenous LA. We also provided evidence that the fetal hypothalamic content of endogenous LA is significantly reduced following maternal exposure to TCDD. Thus, the data obtained strongly suggest that TCDD reduces the expression of fetal pituitary gonadotropins to imprint sexual immaturity or disturb development by suppressing the level of LA, one of the key players serving energy production.</p> </div
A Survey of Playground Environments in Early Childhood Education and Care( ECEC) Settings
The quality of Early Childhood Education and Care (ECEC) outside environments is becoming an important theme, but not enough is known yet about the settings and practices in Japanese playgrounds. To discuss the way to guarantee the quality of children’s experiences, studies were reviewed for foreign countries and Japan, and research was done about playgrounds and outside environments in 1,740 Japanese centers. Similarities and differences between centers were shown, evaluationg scales were made from results, and some important ideas of practice were revealed. In conclusion, there are many differences between outside settings of centers. Practices that have longitudinal view, understanding of surroundings, and enough communication between staffs lead to richer environments. The important points from both tangible and intangible elements of centers’ environments should be clarified
A Review of Studies on Playgrounds and Outdoor Environments
Research on the environment of the playgrounds and similar outdoor environments in Early Childhood Education and Care (ECEC) is progressing, but the perspectives of these studies are not well known. In order to determine how previous studies view playground and outdoor environments from global perspectives, this research reviews domestic and foreign playgrounds and outdoor environments focusing on five points: history, value and rule, development and recognition, function, and methodology. It is necessary for the overarching and multiple visual lines to look at the researches of playground and outdoor environments in ECEC with regards to the development of children, the functions of these environments, the values and rules while considering history and various methodologies. Our future playground research will incorporate outdoor activities and regional resources as an expanded look into the garden, to discuss it from various viewpoints
The LA-specific recovery from a TCDD-induced reduction in the fetal expression of gonadotropins: A–C, pituitary levels of LHβ, FSHβ and LH/FSH α-subunit mRNAs, respectively; and D, serum content of LH.
<p>Gonadotropin mRNAs in the fetuses (GD20), the parents of which were treated with TCDD (GD15) and anti-oxidants (GD15-20), were determined by RT-PCR. The level of gonadotropin mRNA was normalized by β-actin mRNA. Serum LH (GD20 fetuses) was determined by ELISA. In the white bar control, pregnant rats were treated with DMSO alone or anti-oxidant dissolved in DMSO. In the shaded bar control, dams were given aqueous NaCl alone or anti-oxidant dissolved in this solution. The pituitaries and sera of all male fetuses in one dam were pooled to become one analytical unit. Each bar represents the mean value relative to the control ± SEM of 5 (panels A-C) or 7 (panel D) dams. *p<0.05 and **p<0.01, from the respective controls (A-C) or between a pair indicated (<i>D</i>).</p
The LA-specific recovery from a TCDD-induced reduction in the fetal expression of testicular StAR and CYP17; A, StAR mRNA; B, StAR protein; C, CYP17 mRNA; and D, CYP17 protein.
<p>The fetal (GD20) testis was analyzed after maternal exposure to TCDD (GD15) and anti-oxidants (GD15-20). The expression of mRNA and protein was analyzed RT-PCR and immunoblotting, respectively. See Materials and Methods for the details of animal treatment and analytical methods. Edaravone is abbreviated as Eda. The levels of StAR and CYP17 mRNAs were normalized by β-actin mRNA. In the white bar control, pregnant rats were treated with DMSO alone or anti-oxidant dissolved in DMSO. In the shaded bar control, dams were given aqueous NaCl alone or anti-oxidant dissolved in this solution. Each bar represents the mean value relative to the control ± SEM of 10 fetuses, each 2 of which were removed from 5 different dams. In processing the data, the values of two fetuses from one dam were averaged to become one analytical unit. Thus, the data are shown as N = 5 dams. *p<0.05 and **p<0.01, from the respective controls (panels A and C) or between a pair indicated (panels B and D).</p
Fetal brain components showing a significant increase or decrease by maternal exposure to TCDD.
<p>The representative components that were shown by PCA to be significantly changed by TCDD are listed. The data from both positive and negative ion modes were combined. The components of the TCA cycle are shown in bold character.</p