Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease

Neurodegenerative disorders (ND) are characterized by the progressive and irreversible loss of neurons. Alzheimer’s Disease (AD) is the most incident age-related ND, in which the presence of a chronic inflammatory compound seems to be related to its pathogenesis. Different stimuli in the central nervous system (CNS) can induce activation, proliferation, and changes in phenotype and glial function, which can be modulated by anti-inflammatory agents. Apigenin (4,5,7–trihydroxyflavone) is a flavonoid found in abundance in many fruits and vegetables, that has shown important effects upon controlling the inflammatory response. This study evaluated the neuroprotective and neuroimmunomodulatory potential of apigenin using in vitro models of neuroinflammation associated with AD. Co-cultures of neurons and glial cells were obtained from the cortex of newborn and embryonic Wistar rats. After 26 days in vitro, cultures were exposed to lipopolysaccharide (LPS; 1 μg/ml), or IL-1β (10 ng/ml) for 24 h, or to Aβ oligomers (500 nM) for 4 h, and then treated with apigenin (1 μM) for further 24 h. It was observed that the treatment with apigenin preserved neurons and astrocytes integrity, determined by Rosenfeld’s staining and immunocytochemistry for β-tubulin III and GFAP, respectively. Moreover, it was observed by Fluoro-Jade-B and caspase-3 immunostaining that apigenin was not neurotoxic and has a neuroprotective effect against inflammatory damage. Additionally, apigenin reduced microglial activation, characterized by inhibition of proliferation (BrdU+ cells) and modulation of microglia morphology (Iba-1 + cells), and decreased the expression of the M1 inflammatory marker CD68. Moreover, as determined by RT-qPCR, inflammatory stimuli induced by IL-1β increased the mRNA expression of IL-6, IL-1β, and CCL5, and decreased the mRNA expression of IL-10. Contrary, after treatment with apigenin in inflammatory stimuli (IL-1β or LPS) there was a modulation of the mRNA expression of inflammatory cytokines, and reduced expression of OX42, IL-6 and gp130. Moreover, apigenin alone and after an inflammatory stimulus with IL-1β also induced the increase in the expression of brain-derived neurotrophic factor (BDNF), an effect that may be associated with anti-inflammatory and neuroprotective effects. Together these data demonstrate that apigenin presents neuroprotective and anti-inflammatory effects in vitro and might represent an important neuroimmunomodulatory agent for the treatment of neurodegenerative conditions

Mining association rules for label ranking

Lecture Notes in Computer Science Volume 6635, 2011.Recently, a number of learning algorithms have been adapted for label ranking, including instance-based and tree-based methods. In this paper, we continue this line of work by proposing an adaptation of association rules for label ranking based on the APRIORI algorithm. Given that the original APRIORI algorithm does not aim to obtain predictive models, two changes were needed for this achievement. The adaptation essentially consists of using variations of the support and confidence measures based on ranking similarity functions that are suitable for label ranking. Additionally we propose a simple greedy method to select the parameters of the algorithm. We also adapt the method to make a prediction from the possibly con icting consequents of the rules that apply to an example. Despite having made our adaptation from a very simple variant of association rules for classification, partial results clearly show that the method is making valid predictions. Additionally, they show that it competes well with state-of-the-art label ranking algorithms.This work was partially supported by project Rank! (PTDC/EIA/81178/2006) from FCT and Palco AdI project Palco3.0 financed by QREN and Fundo Europeu de Desenvolvimento Regional (FEDER). We thank the anonymous referees for useful comments

Toward an internally consistent astronomical distance scale

Accurate astronomical distance determination is crucial for all fields in astrophysics, from Galactic to cosmological scales. Despite, or perhaps because of, significant efforts to determine accurate distances, using a wide range of methods, tracers, and techniques, an internally consistent astronomical distance framework has not yet been established. We review current efforts to homogenize the Local Group's distance framework, with particular emphasis on the potential of RR Lyrae stars as distance indicators, and attempt to extend this in an internally consistent manner to cosmological distances. Calibration based on Type Ia supernovae and distance determinations based on gravitational lensing represent particularly promising approaches. We provide a positive outlook to improvements to the status quo expected from future surveys, missions, and facilities. Astronomical distance determination has clearly reached maturity and near-consistency.Comment: Review article, 59 pages (4 figures); Space Science Reviews, in press (chapter 8 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age