61 research outputs found

    Upregulation of CRABP1 in human neuroblastoma cells overproducing the Alzheimer-typical Aβ42 reduces their differentiation potential

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    <p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is characterized by neurodegeneration and changes in cellular processes, including neurogenesis. Proteolytic processing of the amyloid precursor protein (APP) plays a central role in AD. Owing to varying APP processing, several β-amyloid peptides (Aβ) are generated. In contrast to the form with 40 amino acids (Aβ<sub>40</sub>), the variant with 42 amino acids (Aβ<sub>42</sub>) is thought to be the pathogenic form triggering the pathological cascade in AD. While total-Aβ effects have been studied extensively, little is known about specific genome-wide effects triggered by Aβ<sub>42 </sub>or Aβ<sub>40 </sub>derived from their direct precursor C99.</p> <p>Methods</p> <p>A combined transcriptomics/proteomics analysis was performed to measure the effects of intracellularly generated Aβ peptides in human neuroblastoma cells. Data was validated by real-time polymerase chain reaction (real-time PCR) and a functional validation was carried out using RNA interference.</p> <p>Results</p> <p>Here we studied the transcriptomic and proteomic responses to increased or decreased Aβ<sub>42 </sub>and Aβ<sub>40 </sub>levels generated in human neuroblastoma cells. Genome-wide expression profiles (Affymetrix) and proteomic approaches were combined to analyze the cellular response to the changed Aβ<sub>42</sub>- and Aβ<sub>40</sub>-levels. The cells responded to this challenge with significant changes in their expression pattern. We identified several dysregulated genes and proteins, but only the cellular retinoic acid binding protein 1 (CRABP1) was up-regulated exclusively in cells expressing an increased Aβ<sub>42</sub>/Aβ<sub>40 </sub>ratio. This consequently reduced all-trans retinoic acid (RA)-induced differentiation, validated by CRABP1 knock down, which led to recovery of the cellular response to RA treatment and cellular sprouting under physiological RA concentrations. Importantly, this effect was specific to the AD typical increase in the Aβ<sub>42</sub>/Aβ<sub>40 </sub>ratio, whereas a decreased ratio did not result in up-regulation of CRABP1.</p> <p>Conclusion</p> <p>We conclude that increasing the Aβ<sub>42</sub>/Aβ<sub>40 </sub>ratio up-regulates CRABP1, which in turn reduces the differentiation potential of the human neuroblastoma cell line SH-SY5Y, but increases cell proliferation. This work might contribute to the better understanding of AD neurogenesis, currently a controversial topic.</p

    La pelle : l'apparato tegumentario : morfologia, struttura e funzioni

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    In questo libro si \ue8 cercato di riassumere tutto ci\uf2 che uno studente di Medicina, di Farmacia, di Scienze, oltre che un buon operatore sanitario e un buon operatore estetico deve sapere sulla pelle e la sua fisiologia, oltre alle sue reazioni, normali e patologiche, alle sollecitazioni innumerevoli che in ogni momento lo colpiscono. La pelle \ue8 la prima barriera che il nostro corpo oppone al mondo esterno, dal quale riceve gran parte delle informazioni necessarie (la pelle \ue8 un grande e sofisticato orghano di senso), ma anche una grande quantit\ue0 di insulti, che spesso noi stessi le prcuriamo con nostro stile di vita (fumo, alcoll, abbronzature insensate ecc.). Ecco allora che conoscerla meglio pu\uf2 essere sicuramente utile, per noi stessi ma anche per gli altri, se la nostra attivit\ue0 sar\ue0 o \ue8 gi\ue0 quella di un operatore nel campo della salute e della bellezza

    Respiratory illness and air pollution from the steel industry: the case of Piquiá de Baixo, Brazil (Preliminary report)

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    Background: This report is based on an independent study carried out by medical professionals of the Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute) in Milan, Italy, and aimed to assess the incidence of respiratory diseases in a Brazilian community (Piquiá de Baixo, in the city of Açailandia) exposed to extreme air pollution in connection to a local steel manufacturing plant. The study has the objective to contribute to the existing literature on the health risks associated with fine particle pollution (PM2.5) due to steel production with data from Brazil. Methods: The study is based on a cross-sectional sample of the resident population of Piquiá de Baixo age 16 or over consisting of 220 people. We collected data about the health conditions of participant subjects in two ways: a) medical history questionnaires and b) clinical assessment of respiratory function through spirometry testing. The results were evaluated based on comparative studies. Results: According to the spirometric tests performed, 28 % of the sample population suffers from respiratory pathologies (for the most part of restrictive rather than obstructive nature). This incidence rate is between six and two times higher than those reported in similar studies carried out in other countries (which range between 4.6 and 14.5 %). In addition, the incidence rate is also significantly high in light of the fact that our sample population did not include the category of subjects most at risk for pulmonary disorders in connection to air pollution caused by the Piquiá steel processing complex: in other words, men and women employed in the steel mills or in connection with their industrial cycle (as many as 434 Piquiá residents age 16 and over were unable to participate to our study due to “work-related reasons”). Conclusions: In light of the above considerations, we believe that our findings contribute to the existing literature on the correlation between pulmonary disease and air pollution in industrialized areas, while warranting further scientific research on the public health consequences of industrial production in Piquiá de Baixo. In turn, on the ethical plane, we believe that research of this nature strengthens the need to advocate for more severe environmental and health policies aimed at limiting the hazards associated with the steel industry in Piquiá and in similar contexts around the world
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