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

The flavonoid agathisflavone modulates the microglial neuroinflammatory response and enhances remyelination

Myelin loss is the hallmark of the demyelinating disease multiple sclerosis (MS) and plays a significant role in multiple neurodegenerative diseases. A common factor in all neuropathologies is the central role of microglia, the intrinsic immune cells of the central nervous system (CNS). Microglia are activated in pathology and can have both pro- and anti-inflammatory functions. Here, we examined the effects of the flavonoid agathisflavone on microglia and remyelination in the cerebellar slice model following lysolecithin induced demyelination. Notably, agathisflavone enhances remyelination and alters microglial activation state, as determined by their morphology and cytokine profile. Furthermore, these effects of agathisflavone on remyelination and microglial activation were inhibited by blockade of estrogen receptor α. Thus, our results identify agathisflavone as a novel compound that may act via ER to regulate microglial activation and enhance remyelination and repair

Comparison of rally times and action effectiveness between professional volleyball and school sub-19

Este estudo teve como objetivo comparar os tempos de rally e o padrão de complexos e de ações realizados no voleibol profissional e escolar sub-19. Foram avaliados um jogo de voleibol masculino e feminino da Superliga Brasileira (voleibol profissional) e um jogo de uma equipa dos Jogos dos Institutos Federais (voleibol escolar sub-19) por meio do software Adobe®Premiere®Pro e analisou-se os tempos de rallies e seus intervalos, a percentagem (%) da densidade, os tipos e números de complexos e das ações nos rallies, além do ponto obtido no rally. Nos jogos de voleibol escolar sub-19 e feminino exibiram maiores tempo de rally e % da densidade, reduzindo o tempo de recuperação. No jogo de voleibol escolar sub-19 realizou-se um maior número de complexos no rally que o profissional. Os complexos com 3 e 1 ações foram os mais executados e exibiram maior ocorrência de pontos. O escalão dos sub-19 mostrou uma maior ocorrência de pontos por meio de erros de fundamentos (bloqueio, defesa e ataque), já nos jogos profissionais ocorreram mais pontos de ataque. Erros de serviço na superliga masculina foram mais relevantes que nas demais categorias. Conclui-se que o voleibol escolar sub-19 difere do profissional nos tempos de rallies e padrões dos complexos e ações, devido à menor experiência no desporto.info:eu-repo/semantics/publishedVersio

Cholesterol-functionalized carvedilol-loaded PLGA nanoparticles: anti-inflammatory, antioxidant, and antitumor effects

The inflammation has been identified as factor of tumor progression, which has increased the interest and use of molecules with anti-inflammatory and antioxidant activities in the cancer treatment. In this study, the antioxidant, anti-inflammatory, and antitumor potentials of carvedilol was explored in a different approach. The cholesterol (CHO) was investigated as facilitated agent in the action of carvedilol-loaded nanoparticles. Different formulations exhibited spherical and stable nanoparticle with mean diameter size < 250 nm. The cholesterol changed the copolymer-drug interactions and the encapsulation efficiency. The in vitro cancer study was performed using murine colorectal cancer cell line (CT-26) to observe the cell viability and apoptosis on MTS assay and flow cytometry, respectively. The experiments have demonstrated that cholesterol improved the performance of drug-loaded nanoparticles, which was much better than free drug. The in vivo inflammation peritonitis model revealed that carvedilol-loaded nanoparticles increased the level of glutathione and leukocyte migration mainly when the functionalized drug-loaded nanoparticles were tested, in a lower dose than the free drug. As hypothesized, the experimental data suggest that cholesterol-functionalized carvedilol-loaded PLGA nanoparticles can be a novel and promising approach in the inflammation-induced cancer therapy since showed anti-inflammatory, antioxidant, and antitumor effects.Graphical abstractRadiolog

Leishmania amazonensis downregulates macrophage iNOS expression via Histone Deacetylase 1 (HDAC1): a novel parasite evasion mechanism.

The induced expression of nitric oxide synthase (iNOS) controls the intracellular growth of Leishmania in infected macrophages. Histones deacetylases (HDACs) negatively regulate gene expression through the formation of complexes containing transcription factors such as NF-κB p50/50. Herein, we demonstrated the occupancy of p50/p50_HDAC1 to iNOS promoter associated with reduced levels of H3K9Ac. Remarkably, we found increased levels of HDAC1 in L. amazonensis-infected macrophages. HDAC1 upregulation was not found in L. major-infected macrophages. The parasite intracellular load was reduced in HDAC1 knocked-down macrophages, which presented increased nitric oxide levels. HDAC1 silencing led to the occupancy of CBP/p300 to iNOS promoter and the rise of H3K9Ac modification. Importantly, the immunostaining of skin samples from hiporeactive cutaneous leishmaniasis patients infected with L. amazonensis, revealed high levels of HDAC1. In brief, L. amazonensis induces HDAC1 in infected macrophages, which contribute to parasite survival and is associated to hiporeactive stage found in L. amazonensis infected patients

Feeding strategies and energy to protein ratio on tambaqui performance and physiology

The objective of this work was to evaluate the effect of feed deprivation and refeeding with diets containing different energy to protein ratios (E/P) on the performance and physiology of juvenile tambaqui (Colossoma macropomum). A 4x2 factorial arrangement with three replicates was used, with four E/P ratios (11.5, 10.5, 9.5, and 8.5 kcal g-1 digestible energy per protein) and two feeding regimens (with and without deprivation), during 60 days. Fish from the food-deprived group were fasted for 14 days and refed from the fifteenth to the sixtieth day, whereas the remaining fish were fed for 60 days. At the end of the experimental period, weight of fish subjected to food deprivation was lower than that of those continuously fed; however, this condition did not influence the physiological parameters analyzed. Tambaqui fed 11.5 kcal g-1 achieved lower final weight than those fed with the other diets, in both regimens. Among the physiological parameters, only plasma protein presented significant increase in fish fed 8.5 kcal g-1, in both feeding regimens, probably due to the higher dietary protein concentration. These results indicate that fish show a partial compensatory growth, and that 10.5 kcal g-1 can be recommended for the diet of juvenile tambaqui

Componentes genéticos aditivos e não aditivos em maracujazeiro-azedo

O objetivo deste trabalho foi avaliar os componentes genéticos aditivos e não aditivos em caracteres qualitativos e produtivos de maracujazeiro, para determinar a ocorrência de efeitos genéticos dominantes. Foram estudados 12 híbridos F1, obtidos entre duas populações distintas, com uso do delineamento II de Comstock e Robinson. Durante o primeiro e o segundo ano (safrinha e primeira safra, respectivamente), foram avaliados os seguintes caracteres: número de frutos por planta, produção estimada, massa de fruto, massa de casca, massa de polpa, comprimento longitudinal, diâmetro equatorial, espessura de casca, teor de sólidos solúveis totais, acidez titulável total e coloração da polpa. A produção do biênio 2004/2005 foi estimada a partir do número total de frutos, multiplicado pela massa média dos frutos. Foram observados efeitos de dominância e, portanto, de heterose, no primeiro ano, para massa de matéria fresca, massa de polpa, massa de casca e diâmetro equatorial do fruto e, no segundo ano, para diâmetro equatorial do fruto e coloração da polpa. Houve predominância dos efeitos aditivos para número de frutos e massa de fruto. Os valores de herdabilidade são indicativos de que a população avaliada pode ser utilizada para a formação da população-base, para promover seleção recorrente