253 research outputs found

    Anti-invasive activity of α-tocopherol against hepatoma cells in culture via protein kinase C inhibition

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    Effects of α-, β-, γ- and δ-tocopherols on the proliferation and invasion of AH109A hepatoma cells and their modes of action were investigated. Four tocopherols inhibited the invasion as well as the proliferation of AH109A cells. Their inhibitory effects were more prominent on the invasion than on the proliferation. At 1 µM, α-tocopherol showed most potent anti-invasive activity without any influence on the proliferation. We have previously demonstrated that reactive oxygen species increase the invasion of AH109A cells. α-Tocopherol suppressed the reactive oxygen species-induced invasion but failed to suppress the reactive oxygen species-induced rises in intracellular peroxide level. GF 109203X, a protein kinase C inhibitor, decreased the invasive activity of AH109A cells. In contrast, phorbol-12-myristate-13-acetate, a protein kinase C activator, increased the invasive capacity of AH109A cells. α-Tocopherol suppressed the phorbol-12-myristate-13-acetate-induced increase in the invasion, and canceled the phorbol-12-myristate-13-acetate-induced rises in protein kinase C activity and phosphorylation of extracellular signal-regulated kinase. These results suggest that tocopherols, especially α-tocopherol, possess inhibitory effect more strongly on the invasion of AH109A cells than on the proliferation. They also suggest that the anti-invasive activity of α-tocopherol is raised through suppression of PKC/ERK signaling

    The quality of life among persons with severe mental illness enrolled in an assertive community treatment program in Japan: 1-year follow-up and analyses

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    BACKGROUND: Toward effective community care for persons with severe mental illness and deinstitutionalization in Japan, we assessed the impact of the first trial of an assertive community treatment program on the lives and subjective perceptions of persons with mental illness without closing hospitals. METHODS: Forty-three subjects were enrolled from the newly admitted patients of a hospital, who met our criteria of problematic hospital use, severity of psychiatric disorders, and behavioral problems. The intervention team aimed to intensively support them in various life domains in their communities to decrease clients' admissions. The Quality of Life Interview was administered at baseline and after 12 months. Data were analyzed to assess the pre-post changes in their QOL, and were explained in association with other descriptive variables. RESULTS: The objective changes included increase in persons whose longest residence in a year were in communities, increase in income, and decrease in family contacts. Most subjective items were not changed except the decrease in satisfaction with family relationships. Satisfaction with family relationships was negatively correlated with hospital days at 1 year follow-up after controlling for symptoms, but was not so at baseline. Also, correlation between satisfaction with family relationships and global well-being was attenuated. A change in the positioning of family by clients and the autonomy of clients were suggested. However, previous studies showed that dissatisfaction with family relationships predicted rehospitalizations independently from symptoms, and our findings suggest our subjects' characteristics and a possible improvement in community-based care. CONCLUSION: Our program predominantly fulfilled the primary goal, but it must be further refined to reflect the detailed characteristics of the target population and resource distribution. Assessing subjective perceptions, or the QOL of clients is useful for evaluating the program localization

    Identification of hepta-histidine as a candidate drug for Huntington's disease by in silico-in vitro- in vivo-integrated screens of chemical libraries.

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    We identified drug seeds for treating Huntington's disease (HD) by combining in vitro single molecule fluorescence spectroscopy, in silico molecular docking simulations, and in vivo fly and mouse HD models to screen for inhibitors of abnormal interactions between mutant Htt and physiological Ku70, an essential DNA damage repair protein in neurons whose function is known to be impaired by mutant Htt. From 19,468 and 3,010,321 chemicals in actual and virtual libraries, fifty-six chemicals were selected from combined in vitro-in silico screens; six of these were further confirmed to have an in vivo effect on lifespan in a fly HD model, and two chemicals exerted an in vivo effect on the lifespan, body weight and motor function in a mouse HD model. Two oligopeptides, hepta-histidine (7H) and Angiotensin III, rescued the morphological abnormalities of primary neurons differentiated from iPS cells of human HD patients. For these selected drug seeds, we proposed a possible common structure. Unexpectedly, the selected chemicals enhanced rather than inhibited Htt aggregation, as indicated by dynamic light scattering analysis. Taken together, these integrated screens revealed a new pathway for the molecular targeted therapy of HD

    Demolition of Reinforced Concrete by Steam Pressure Cracking System

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    The authors developed an environment-friendly demolition mechanical system for a large reinforced concrete structure for an actual site. The steam pressure cracking agent (SPC, non-explosive) is a method that can safely and quickly separate concrete because it produces lesser vibration and sound than the blasting method, which uses explosives. The authors showed that the direction of cracking can be controlled by an induction hole. The principle of control is that the elastic wave of the compression stress generated from the SPC reaction changes to a tensile elastic wave at the induction hole, which initiates a crack. Furthermore, in the SPC method, a large amount of concrete powder generated by the explosion method was not produced, and there was no risk of secondary contamination by fine concrete powder. The area over which the crack propagated depends on the energy generated from the SPC. The relationship between the two is linear. For reinforced concrete, the energy of the SPC is used for both the destructive energy of the concrete and the energy of the cutting of the reinforcing steel bar, which quickly breaks with low energy. By applying an SPC to dismantle large reinforced concrete structures, controlled cracking can be achieved safely and quickly without any environmental pollution. A fracturing method using a SPC is an effective method for the decommissioning of nuclear power plants and the dismantling of concrete structures. In this report, we report a remote drilling system that can be used to remotely install loading holes and guiding holes for the SPC and perform effective controlled fracturing

    PAX2 promoted prostate cancer cell invasion through transcriptional regulation of HGF in an in vitro model

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    AbstractElucidating the mechanism of prostate cancer cell invasion may lead to the identification of novel therapeutic strategies for its treatment. Paired box 2 (PAX2) and hepatocyte growth factor (HGF) proteins are promoters of prostate cancer cell invasion. We found that PAX2 protein activated the HGF gene promoter through histone H3 acetylation and upregulated HGF gene expression. Deletion analysis revealed that the region from −637 to −314 of the HGF gene was indispensable for HGF promoter activation by PAX2. This region contains consensus PAX2 binding sequences and mutations of the sequences attenuated HGF promoter activation. Using an in vitro invasion model, we found that PAX2 and HGF promoted prostate cancer cell invasion in the same pathway. Knockdown of HGF expression attenuated the cells' invasive capacity. Moreover, in tissue samples of human prostate cancers, HGF and PAX2 expression levels were positively correlated. These results suggested that upregulation of HGF gene expression by PAX2 enhanced the invasive properties of prostate cancer cells. The PAX2/HGF pathway in prostate cancer cells may be a novel therapeutic target in prostate cancer patients

    Elastic Wave Property of Concrete Decomposed by Steam Pressure Cracking Agent

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    A steam pressure cracking (SPC) agent is a method that can dismantle concrete safely and quickly. In previous studies, the authors showed that the direction of the crack could be controlled by the tensile stress at the induction holes and not by the compressive stress at the SPC hole. We demonstrate that the compression elastic wave changes to a tensile wave when the wave is reflected at the free surface of the induction hole. We also examined the properties of the concrete by developing an elastic wave measuring system that is difficult to break down even in high-temperature, wet, and radiation environment. The elastic wave velocity change in the four concrete types was less than 4%. It was found that the standard deviation value, σ, changed four times. Therefore, it is possible to determine the deterioration of the internal structure of concrete using the standard deviation value σ, which indicates the dispersion of the elastic wave velocity
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