Charakterisierung der Leukozytensubpopulationen nach magnetischer Tumorzelldepletion

Vom Primum in die Zirkulation entlassene Tumorzellen werden als eine der Hauptursachen für die hämatogene Metastasierung angesehen. Ausgehend von der Prämisse, dass eine Reduktion der Anzahl zirkulierender Tumorzellen im peripheren Blut mit einer Abnahme des Metastasenrisikos verbunden ist, scheint es erstrebenswert, Verfahren zur Depletion dieser Zellen zu entwickeln. Die magnetbasierte Zellseparation unter Verwendung polysaccharidumhüllter Nanopartikel hat sich dafür als geeignet erwiesen. Partikel mit einer Größe im Nanometerbereich können von Zellen über endozytotische Vorgänge inkorporiert werden. Dabei führt die Umhüllung mit Dextran-Derivaten zu einer zelltypspezifischen Interaktion. Tumorzellen zeigen i. d. R. eine rasche Aufnahmekinetik, während Leukozyten durch langsamere Interaktion mit den Magnetpartikeln charakterisiert sind, was die magnetbasierte Separation beider Zellpopulationen ermöglicht. Ziel dieser Arbeit war, den Einfluss von Inkubation mit Nanopartikeln und Separation auf die Leukozyten und ihre Verteilung zu analysieren. Die Untersuchungen erfolgten an Leukozyten aus dem Vollblut Gesunder sowie von Mammakarzinompatientinnen. Die Verteilung der Leuko- und Lymphozytensubpopulationen in der Negativfraktion (unmarkierte Zellen) wird durch die Separation nicht wesentlich verändert, was die Möglichkeit der Retransfusion dieser Fraktion an den Patienten ohne schwere Beeinflussung des Immunstatus beinhaltet. Beim Vergleich zwischen Gesunden und Tumorpatienten zeigten sich kaum signifikante Unterschiede. Die Art der Polysaccharidhülle beeinflusst das Interaktionspotential zwischen Partikeln und Zellen. Die unterschiedlichen Beladungsraten unter Verwendung von CMD, CMC und CMCu als Hüllstoff fanden sich analog für alle Leukozytensubklassen wieder. Die Favorisierung von CMD-Partikeln zur Tumorzelldepletion wird hier nochmals unterstrichen. Die Integrität und Funktionalität der unmarkierten Leukozyten nach der Separation konnte bewiesen werden

Peroxisome Proliferator-Activated Receptor Alpha Target Genes

The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARα governs biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARα is directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPARα target genes. The emphasis is on gene regulation by PPARα in liver although many of the results likely apply to other organs and tissues as well

Non‐stimulated regions in early visual cortex encode the contents of conscious visual perception

Predictions shape our perception. The theory of predictive processing poses that our brains make sense of incoming sensory input by generating predictions, which are sent back from higher to lower levels of the processing hierarchy. These predictions are based on our internal model of the world and enable inferences about the hidden causes of the sensory input data. It has been proposed that conscious perception corresponds to the currently most probable internal model of the world. Accordingly, predictions influencing conscious perception should be fed back from higher to lower levels of the processing hierarchy. Here, we used functional magnetic resonance imaging and multivoxel pattern analysis to show that non-stimulated regions of early visual areas contain information about the conscious perception of an ambiguous visual stimulus. These results indicate that early sensory cortices in the human brain receive predictive feedback signals that reflect the current contents of conscious perception

Synergistic effects of IL-4 and TNFα on the induction of B7-H1 in renal cell carcinoma cells inhibiting allogeneic T cell proliferation

BACKGROUND: The importance of B7-H molecules for the T cell/tumor communication and its impact on renal cell carcinoma (RCC) progression and prognosis has been recently described. Cytokine treatment of RCC has earlier been shown to be beneficial in preclinical settings, but its clinical implementation has not proven to be as effective. This might be partially explained by the yet incomplete picture of cellular alterations in tumor cells upon cytokine treatment investigated in detail in this study. METHODS: RCC tumor cell lines were treated with different cytokines alone or in combination. The constitutive and/or cytokine-induced expression of cytokine receptors signaling components and B7-H molecules in RCC cells were analysed by qPCR and flow cytometry. A mcherry reporter gene construct containing B7-H1 promoter was cloned and its activity was determined upon transfection in cytokine-stimulated cells. Cytokine pretreated tumor cells were co-cultured with allogeneic CD8(+) T cells from healthy donors and T cell proliferation as well as cytokine secretion was determined. RESULTS: A heterogeneous, but constitutive B7-H1,-H2,-H3 and H4 expression was found on human RCC cell lines. IL-4 and TNFα treatment led to strong synergistic induction of B7-H1 in RCC cells, whereas B7-H2 was only increased by TNFα. In contrast, B7-H3 and B7-H4 expression were not altered by these cytokines. Treatment of RCC cells with TNFα and IL-4 was accompanied by an activation of signaling molecules like NF-κB, IκB and STAT6. The cytokine-mediated up-regulation of B7-H1 was due to transcriptional control as determined by an increased B7-H1 promoter activity in the presence of IL-4 and TNFα. Despite HLA class I and LFA-1 were also increased, the cytokine-mediated up-regulation of B7-H1 was more pronounced and caused an inhibition of allospecifc CD8(+) T cell proliferation. CONCLUSION: Thus, IL-4 and TNFα, which could be released by immune cells of the tumor microenvironment, are able to control the B7-H1 expression in RCC thereby altering T cell responses. These data are of importance for understanding the complex interplay of tumor cells with immune cells orchestrated by a number of different soluble and membrane bound mediators and for the implementation of check point antibodies directed against B7-H1

Centriole Assembly Requires Both Centriolar and Pericentriolar Material Proteins

AbstractCentrioles organize pericentriolar material to form centrosomes and also template the formation of cilia. Despite the importance of centrioles in dividing and differentiated cells, their assembly remains poorly understood at a molecular level. Here, we develop a fluorescence microscopy-based assay for centriole assembly in the 1-cell stage C. elegans embryo. We use this assay to characterize SAS-6, a centriolar protein that we identified based on its requirement for centrosome duplication. We show that SAS-6, a member of a conserved metazoan protein family, is specifically required for new centriole assembly, a result we confirm by electron microscopy. We further use the centriole assembly assay to examine the roles of three pericentriolar material proteins: SPD-5, the kinase aurora-A, and γ-tubulin. Our results suggest that the pericentriolar material promotes daughter centriole formation by concentrating γ-tubulin around the parent centriole. Thus, both centriolar and pericentriolar material proteins contribute to centriole assembly

Specific probiotics in elite athlete injuries: indication for usage / Probiotics específicos em lesões de atletas elite: indicação de uso

More severe effects of illness that require probiotic intervention and complete cessation of training activities might have a larger effect on competitive sport performance. In this review, we outline key principles of prevention for injury and illness in high level athletes using probiotic treatments, examine relevant scientific evidence on probiotics for reducing the risk of illness and injury, and summarize practical recommendations for high level athletes, coaches, and practitioners. Studies were obtained through manual and electronic journal searches, review articles, as well as personal correspondence, concerning the period 2000-2018. We used the following databases: PubMed, Web of Science, SCOPUS and Medline. Electronic databases were searched using keywords and/or MeSH terms such as [[[Athlete] or [Sport effects] or [Injuries] or [Disease] or [Allergy] or [Illness] or [Sickness] or [Desorder]] in combination with [[microbiota] or [microbiotas] or [Microbiome] or [microbiomes] or [Human Microbiome] or [Human microbiomes] or [microbiomes, Human] or [Microbiome, Human]] not [[disease]]], until February 18th, 2018. In this present review, we have outlined key points of injury and illness prevention for elite athletes using probiotic treatments, examining relevant scientific evidence on probiotics for reducing the risk of illness and injury, and summarized practical recommendations for high level athletes, coaches, and practitioners

Sex Differences in the Association between Level of Childhood Interleukin-6 and Insulin Resistance in Adolescence

The purpose of this study was to determine whether levels of interleukin-6 (IL-6) in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO2peak) moderate this relationship. Methods. 292 nine-year-old children (n = 292) were followed for 4 years. Anthropometrics and VO2peak were measured. Fasting blood samples were analyzed for IL-6, insulin, and glucose. Homeostasis model assessment (HOMA-IR) was used as a measure of insulin resistance. Results. For girls but not boys, levels of IL-6 at age 9 yrs correlated with HOMA-IR at age 13 yrs: r = 0.223, P = 0.008. Girls with IL-6 levels within the highest quartile at age 9 yrs had an odds ratio of 3.68 (CI = 1.58–8.57) being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence, but only for girls

Capsicum baccatum red pepper prevents cardiometabolic risk in rats fed with an ultra-processed diet

Metabolic syndrome is a serious health condition reaching epidemic proportions worldwide and is closely linked to an increased risk of cardiovascular problems. The lack of appropriate treatment paves the way for developing new therapeutic agents as a high priority in the current research. In this study, we evaluated the protective effects of Capsicum baccatum red pepper on metabolic syndrome scenarios induced by an ultra-processed diet in rats. After four months, the ultra-processed diet increased central obesity, triglycerides, total cholesterol, LDL-cholesterol plasma levels, and impaired glucose tolerance. The oral administration of C. baccatum concomitantly with the ultra-processed diet avoided the accumulation of adipose tissue in the visceral region, reduced the total cholesterol and LDL fraction, and improved glucose homeostasis, factors commonly associated with metabolic syndrome. The data presented herein reveal an important preventive action of C. baccatum in developing metabolic disorders among animals fed a hypercaloric diet, significantly reducing their cardiometabolic risk. Allied with the absence of toxic effects after chronic use, our study suggests C. baccatum red pepper as a secure and enriched source of bioactive compounds promising to protect against pathological processes associated with metabolic syndrome

The reinvention of everyday life in times of pandemic

Em 2020, o Estatuto da Criança e do Adolescente (ECA) faz 30 anos. Esse marco coincide com a pandemia causada pela COVID-19, que coloca em conflito noções de direito ligadas à preservação da vida e da liberdade apresentadas pelo próprio ECA. Diante desse contexto, este artigo trata a respeito de reinvenções e deslocamentos diante da quarentena, os quais se pautam pelo direito à vida ao mesmo tempo em que restringem o direito à liberdade. Ao assumir a inseparabilidade que Michel de Certeau postula quanto às noções de estratégia e tática, o artigo explora, metodologicamente, seis cenas expressivas da reinvenção do cotidiano – e que estão vinculadas, cada uma a seu modo, a três dimensões específicas: a relação de famílias com as tecnologias; a relação das famílias com a escola; e a relação das famílias com suas crianças. As quatro cenas iniciais, exploradas a partir da configuração de estratégia, indicam esforços para a conformação das formas de organização do social. Neste caso, fica evidente como, de um lado, a relação das famílias com as tecnologias, e, de outro, a relação das famílias com a escola sugerem práticas comprometidas com a manutenção de formas de existir, mesmo em meio a um contexto de excepcionalidade. As duas últimas cenas, situadas a partir da configuração de tática, dão visibilidade às práticas cotidianas das famílias com suas crianças, ou seja, ao que entendemos serem relatos de pessoas ordinárias e que, justamente por meio dessa condição, apontam possibilidades de criação do novo.In 2020 the Brazilian Child and Adolescent Statute (ECA) turns 30 years old. This milestone coincides with the pandemic caused by COVID-19, putting in conflict notions of people’s rights linked to the preservation of life and freedom presented by ECA itself. This article explores the reinventions and displacements resulting from the quarantine, which attend to people’s right to life in a context where restrictions are imposed to their right to freedom. By assuming the inseparability of Michel de Certeau’s concepts of ‘strategy’ and ‘tactics’, the article methodologically deals with six expressive scenes of a new practice of everyday life, which are linked, each one in its own way, to three specific dimensions: the families’ relationship with technologies; the relationship of families with the school; and the relationship between families and their children. The four initial scenes, explored from the configuration of ‘strategy’, indicate efforts to shape the forms of social organization. In this case, it becomes evident how, on the one hand, the relationship of families with technology, and, on the other, the relationship of families with school, suggest practices that are committed to maintain ways of existence, even in the midst of a context of exceptionality. The last two scenes are based on the ‘tactic’ configuration and give visibility to everyday practices of families with children, which we view as ordinary people’s reports that, through this very condition, suggest creative possibilities