Phorbol esters have a dual action through protein kinase C in regulation of proliferation of FRTL-5 cells

AbstractIn quiescent rat thyroid (FRTL-5) cells, phorbol-12-myristate-13-acetate (PMA) inhibited DNA synthesis induced by a combination of insulin and thyrotropin (TSH) or dibutyryl cyclic AMP (Bt2cAMP). This inhibitory effect of PMA was observed even when PMA was added after addition of these growth factors, and was maximal when PMA was added 2–4 h after the growth factors (late in the G1-phase of the cell cycle). On the other hand, PMA alone induced DNA synthesis and also enhanced that induced by Bt2cAMP or insulin in these quiescent cells. 1-Oleoyl-2-acetylglycerol mimicked these effects of PMA, but 4α-phorbol-12,13-didecanoate had no effect. These data demonstrate that in FRTL-5 cells protein kinase C has a stimulatory effect on the G0 to G1 transition and an inhibitory effect on the G1 to S transition in the cell cycle

Treatment of Marmoset Intracerebral Hemorrhage with Humanized Anti-HMGB1 mAb

Intracerebral hemorrhage (ICH) is recognized as a severe clinical problem lacking effective treatment. High mobility group box-1 (HMGB1) exhibits inflammatory cytokine-like activity once released into the extracellular space from the nuclei. We previously demonstrated that intravenous injection of rat anti-HMGB1 monoclonal antibody (mAb) remarkably ameliorated brain injury in a rat ICH model. Therefore, we developed a humanized anti-HMGB1 mAb (OKY001) for clinical use. The present study examined whether and how the humanized anti-HMGB1 mAb ameliorates ICH injury in common marmosets. The results show that administration of humanized anti-HMGB1 mAb inhibited HMGB1 release from the brain into plasma, in association with a decrease of 4-hydroxynonenal (4-HNE) accumulation and a decrease in cerebral iron deposition. In addition, humanized anti-HMGB1 mAb treatment resulted in a reduction in brain injury volume at 12 d after ICH induction. Our in vitro experiment showed that recombinant HMGB1 inhibited hemoglobin uptake by macrophages through CD163 in the presence of haptoglobin, suggesting that the release of excess HMGB1 from the brain may induce a delay in hemoglobin scavenging, thereby allowing the toxic effects of hemoglobin, heme, and Fe2+ to persist. Finally, humanized anti-HMGB1 mAb reduced body weight loss and improved behavioral performance after ICH. Taken together, these results suggest that intravenous injection of humanized anti-HMGB1 mAb has potential as a novel therapeutic strategy for ICH

Relationship between physical activity and cerebral white matter hyperintensity volumes in older adults with depressive symptoms and mild memory impairment: a cross-sectional study

IntroductionCerebral white matter hyperintensities (WMHs) are commonly found in the aging brain and have been implicated in the initiation and severity of many central nervous system diseases. Furthermore, an increased WMH volume indicates reduced brain health in older adults. This study investigated the association between WMH volume and physical activity in older adults with depressive symptoms (DS) and mild memory impairment (MMI). Factors associated with the WMH volume were also investigated.MethodsA total of 57 individuals aged over 65 years with DS and MMI were included in this study. The participants underwent magnetic resonance imaging to quantify WMH volumes. After WMH volume was accumulated, normalized to the total intracranial volume (TIV), the percentage of WMH volume was calculated. In addition, all participants wore a triaxial accelerometer for 2 weeks, and the average daily physical activity and number of steps were measured. The levels of blood biomarkers including cortisol, interleukin-6 (IL-6), brain-derived insulin-like growth factor-1, and brain-derived neurotrophic factor were measured. Motor and cognitive functions were also assessed.ResultsFaster maximum walking speed and longer time spent engaged in moderate physical activity were associated with a smaller percent of WMH volume, whereas higher serum IL-6 levels were associated with a larger percent of WMH volume. The number of steps per day, time spent engaged in low levels of physical activity, cognitive function, and all other measured biomarkers were not significantly associated with percent of WMH volume.DiscussionHigher blood inflammatory cytokine levels, shorter duration of moderate physical activity, and lower maximum walking speed were associated with a higher percent of WMH volume. Our results provide useful information for maintaining brain health in older adults at a high risk of developing dementia and may contribute to the development of preventive medicine for brain health

Produção de ácido acrílico a partir da oxidação catalítica do propileno

Trabalho de Conclusão de Curso (graduação)—Universidade de Brasília, Instituto de Química, 2017.O propósito deste trabalho foi realizar uma avaliação da implementação de uma planta de produção de ácido acrílico 99,9% a partir da oxidação parcial do propileno em um reator de leito fluidizado com catalisadores metálicos heterogêneos. Com esse objetivo, foi realizada a simulação do processo com a utilização do programa Aspen HYSYS a partir das especificações iniciais do projeto. Em seguida, com os dados fornecidos pelo simulador, foram efetuados os cálculos dos parâmetros de design dos equipamentos, além das tubulações e sistemas de segurança, com fins de determinação do ótimo econômico de toda planta para, então, proceder-se à avaliação financeira considerando-se, também, o preço dos reagentes e produtos aliado à quantidade utilizada destes e o mercado financeiro de 2017 para o produto desejado e, assim, provar a viabilidade da instalação do sistema de produção no complexo industrial. A capacidade da planta permitirá uma produção em larga escala do composto, o qual será destinado a diversas utilizações, como fabricação de adesivos, papéis, tecidos, tintas, vernizes, revestimentos, couro, entre outros.The purpose of this work was to make an evaluation of the implementation of a plant for the production of acrylic acid 99,9% starting from the partial oxidation of propylen in a fluidized bed reactor with heterogeneous metallic catalysts. With that objective, a simulation of the process was made utilizing Aspen HYSYS program, with the initial specifications for the project. Afterwards, with the data provided by the simulator, the calculation of the design parameters of the equipments, including pipes and security systems to determine the overall economical optimum to proceed to the financial evaluation, also considering the reagent and product prices, allied to their respective quantities used in the plant, and the financial market in 2017 for the desired product and, by this, prove the viability of the installation of the production system in the industrial complex. The plant capacity will allow a large scale production of the compound, which will be destined to various uses, like the fabrication of adhesives, papers, textiles, paints, varnishes, coating, among others