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

EFEITO DA BIOESTIMULAÇÃO, MONENSINA E SOMATOTROPINA RECOMBINANTE BOVINA SOBRE O GANHO MÉDIO DIÁRIO E INÍCIO DA PUBERDADE EM NOVILHAS GIROLANDO CRIADAS A PASTO

To evaluate the effect of three management strategies on ovarian function of Girolando heifers raised in a pasture-based system, 80 females with 10 months of age and weight 169,3 ± 26,4 kg were divided in eight groups and submitted by 180 days to the treatments: Control (T1); Biostimulation (T2); Monensin (T3); Recombinant bovine somatotropin (BST) (T4); Biostimulation and Monensin (T5); Biostimulation and BST (T6); Monensin and BST (T7); Biostimulation, Monensin and BST (T8). Oestrus activity was evaluated daily and heifers were weighted every 15 days. Starting from the 15th month of age animals were submitted to ovarian evaluation by ultrasound to verify follicles and corpus luteum. Daily weight gain (kg) was 0,52 ± 0,02 (T1); 0,42 ± 0,03 (T2); 0,68 ± 0,04 (T3); 0,43 ± 0,03 (T4); 0,42 ± 0,04 (T5); 0,42 ± 0,02 (T6); 0,70 ± 0,04 (T7) and 0,53 ± 0,01 (T8), with differences (P<0,05). Weight on the 16th month of age varied from 270 kg (T2) to 323 kg (T3), with differences (P<0,05). The signals of oestrus where observed in females starting from the 13th month of age and the higher concentration of these signals being observed at the 14th (T8) and 15th (T3), compatible with the ovarian activity to the 15 months when the animals of these groups had antral follicles or corpus luteum. The present results allow to conclude that the offer of monensin to pre-pubertal Girolando heifers, alone or in association with bioestimulation and BST allows homogenizing the age at puberty in pasture-based systems, reducing the age of the first service and calving.Com o objetivo de avaliar o efeito de três estratégias de manejo sobre a função ovariana de novilhas Girolando criadas a pasto, 80 fêmeas com 10 meses de idade e peso de 169,3 ± 26,4 kg foram alocadas em oito grupos e submetidas por 180 dias aos tratamentos: Controle (T1); Bioestimulação (T2); Monensina (T3); Somatotropina Recombinante Bovina - rBST (T4); Bioestimulação e Monensina (T5); Bioestimulação e rBST (T6); Monensina e rBST (T7); Bioestimulação, Monensina e rBST (T8). A atividade estral foi avaliada diariamente e os pesos tomados a cada 15 dias. Entre 15 e 16 meses de idade as fêmeas foram submetidas à ultra-sonografia ovariana, a fim de verificar folículos e corpos lúteos. O ganho médio diário (kg) foi 0,52 ± 0,02 (T1); 0,42 ± 0,03 (T2); 0,68 ± 0,04 (T3); 0,43 ± 0,03 (T4); 0,42 ± 0,04 (T5); 0,42 ± 0,02 (T6); 0,70 ± 0,04 (T7) e 0,53 ± 0,01 (T8), verificando-se diferenças entre eles (P<0,05). O peso aos 16 meses variou de 270 kg (T2) a 323 kg (T3), com diferenças (P<0,05). Os sinais de estro foram observados nas fêmeas a partir de 13 meses de idade e verificou-se maior concentração destes sinais aos 14 (T8) e aos 15 meses (T3), compatível com a atividade ovariana aos 15/16 meses, quando os animais destes grupos tinham folículos antrais e/ou corpos lúteos. Estes resultados permitem concluir que a adição de monensina à alimentação de fêmeas Girolando pré-púberes isolada ou associada com bioestimulação e aplicação de rBST permite homogeneizar a idade à puberdade de animais criados a pasto, reduzindo a idade ao primeiro serviço e parto

Beyond Patient Characteristics: A Narrative Review of Contextual Factors Influencing Involuntary Admissions in Mental Health Care

Variations in the rates of involuntary admission (IA) reflect the influence of unexplained contextual variables that are typically too heterogeneous to be included in systematic reviews. This paper attempts to gather and analyze factors unrelated to the patients that have been linked to IA. The articles included in this review were selected by iteratively searching four electronic databases (PubMed, PsychINFO, EMBASE, and Web of Science). A total of 54 studies from 19 different countries and regions, including 14 European countries, the United States, Canada, China, Vietnam, and Taiwan, were selected. The factors were categorized as service-related factors, impactful events, seasonal and temporal factors, mental health legislation, staff factors, and public attitudes. The factors rarely act in isolation but rather interact and reinforce each other, causing a greater influence on IA. This paper explains how these factors present opportunities for robust and sustainable interventions to reduce IAs. The paper also identifies future directions for research, such as examining the effects of economic recessions. Enhancing global reporting standards is essential to validate future research and support further in-depth studies. The complexity of the factors influencing IA and the implicit role of society suggest that resolving it will require social change

Chronic lead intoxication in a jaguar (Panthera onca) shot with round lead pellets - case report

ABSTRACT Lead is a heavy metal and an important cause of acute or chronic toxicosis in humans, domestic, and wild animals. This report aims to describe a case of chronic lead poisoning in a jaguar (Panthera onca) kept under human care that was rescued from the wild environment. The animal was rescued in poor condition in 2004 and kept under human care at the Belo Horizonte Zoological Garden (Minas Gerais, Brazil) until 2020, when it presented with anorexia, vomiting and ataxia. Over the past years the animal had episodes of anemia and increased serum urea and creatinine. Radiography demonstrated 21 radiopaque projectiles on the right side of the face. At necropsy there were multiple projectiles surrounded by fibrous tissue in the subcutaneous of the right side of the face, fibrinous peritonitis, multiple gastric ulcers, and melena. The lead dosage was performed using the atomic absorption spectrometry technique using renal tissue collected at necropsy, with a result of 908 ppb (µg/kg). The findings of projectiles associated with the dosage of lead above the reference limits allow the diagnosis of chronic intoxication in this case

Antifungal activity of propolis against Fonsecaea pedrosoi, a chromoblastomycosis agent

Chromoblastomycosis is a subcutaneous mycosis caused by dematiaceous fungi, being Fonsecaea pedrosoi the main etiologic agent in Brazil. Propolis is a resinous material collected by honeybees, with variable composition and pharmacological properties, including antifungal activity. The antifungal activity of ethanolic extracts of propolis (EEP) obtained from different municipalities of the state of Rio Grande do Sul, Brazil, against F. pedrosoi strains was assessed. The EEP showed MIC values between 625 and 2500 µg/mL and the best antifungal activity were obtained with the propolis collected in Santo Antônio da Patrulha and Candelária. All extracts showed the presence terpenoids with similar chromatographic behavior while flavonoids were abundant in the most active samples. The quantification of phenolic compounds demonstrated that there is no correlation between their concentration and antifungal activity. Thus, it can be concluded that the activity is linked to a qualitative chemical composition and not to the general amount of phenolic compoundsColegio de Farmacéuticos de la Provincia de Buenos Aire

Photoinduced transformation of waste-derived soluble bio-based substances

[EN] Waste-derived, soluble bin-based substances (SBO), are effective low-cost photosensitizers that could find application in pollutant photodegradation. For this reason, it is important to understand if and to what extent irradiation could modify their properties. The exposure of SBO to simulated sunlight induced important spectral and structural modifications. Both the whole material and its acid-soluble fraction were characterized, highlighting several properties in common with humic and fulvic substances, including absorption spectra, specific absorbance and fluorescence behavior. The latter was described with a three-component model using PARAFAC analysis. Irradiation induced SBO photobleaching, but the absorbance of the acid-soluble fraction increased with irradiation. This finding suggests a progressive photochemical solubilization of SBO, which is confirmed by the increase of the carboxylic groups. In addition to absorbance, the fluorescence of whole SBO was also decreased by irradiation, thereby suggesting that both chromophores and fluorophores were photodegraded. The increasingly hydrophilic character given to SBO by irradiation also accounted for the photoinduced decrease of the surfactant properties of the material. (C) 2015 Elsevier B.V. All rights reserved.This work was funded by the 7thFP IRSES-2010-269128-EnvironBos Marie Curie Action and by Ministero delle Politiche Agricole e Forestali (Agrienergia project). The authors are grateful to the following private and/or public Italian institutions: (a) Acea Pinerolese Spa in Pinerolo (TO) for supplying the SBO sourcing materials; (b) Studio Chiono ed Associati in Rivarolo Canavese (TO) for making available pilot equipment and services for the production of the SBO.Avetta, P.; Berto, S.; Bianco Prevot, A.; Minella, M.; Montoneri, E.; Persico, D.; Vione, D.... (2015). Photoinduced transformation of waste-derived soluble bio-based substances. Chemical Engineering Journal. 274:247-255. https://doi.org/10.1016/j.cej.2015.03.126S24725527

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Search for a Higgs Boson Decaying to Weak Boson Pairs at LEP

A Higgs particle produced in association with a Z boson and decaying into weak boson pairs is searched for in 336.4 1/pb of data collected by the L3 experiment at LEP at centre-of-mass energies from 200 to 209 GeV. Limits on the branching fraction of the Higgs boson decay into two weak bosons as a function of the Higgs mass are derived. These results are combined with the L3 search for a Higgs boson decaying to photon pairs. A Higgs produced with a Standard Model e+e- --> Zh cross section and decaying only into electroweak boson pairs is excluded at 95% CL for a mass below 107 GeV

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types