Phytoestrogen agathisflavone ameliorates neuroinflammation-induced by LPS and IL-1β and protects neurons in cocultures of glia/neurons

Inflammation and oxidative stress are common aspects of most neurodegenerative diseases in the central nervous system. In this context, microglia and astrocytes are central to mediating the balance between neuroprotective and neurodestructive mechanisms. Flavonoids have potent anti-inflammatory and antioxidant properties. Here, we have examined the anti-inflammatory and neuroprotective potential of the flavonoid agathisflavone (FAB), which is derived from the Brazilian plant Poincianella pyramidalis, in in vitro models of neuroinflammation. Cocultures of neurons/glial cells were exposed to lipopolysaccharide (LPS, 1 µg/mL) or interleukin (IL)-1β (10 ng/mL) for 24 h and treated with FAB (0.1 and 1 µM, 24 h). FAB displayed a significant neuroprotective effect, as measured by nitric oxide (NO) production, Fluoro-Jade B (FJ-B) staining, and immunocytochemistry (ICC) for the neuronal marker β-tubulin and the cell death marker caspase-3, preserving neuronal soma and increasing neurite outgrowth. FAB significantly decreased the LPS-induced microglial proliferation, identified by ICC for Iba-1/bromodeoxyuridine (BrdU) and CD68 (microglia M1 profile marker). In contrast, FAB had no apparent effect on astrocytes, as determined by ICC for glial fibrillary acidic protein (GFAP). Furthermore, FAB protected against the cytodestructive and proinflammatory effects of IL-1β, a key cytokine that is released by activated microglia and astrocytes, and ICC showed that combined treatment of FAB with α and β estrogen receptor antagonists did not affect NF-κB expression. In addition, qPCR analysis demonstrated that FAB decreased the expression of proinflammatory molecules TNF-α, IL-1β, and connexins CCL5 and CCL2, as well as increased the expression of the regulatory molecule IL-10. Together, these findings indicate that FAB has a significant neuroprotective and anti-inflammatory effect in vitro, which may be considered as an adjuvant for the treatment of neurodegenerative diseases

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

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Fuel Cell Vehicle Configuration Trend Analysis

INTRODUCTION All over the world the environmental issue has been increasingly focused. In most countries the land transport system makes use of fossil fuels only and, as a consequence, it is dependent on the vulnerability, supply and volatility of the international oil market prices. For example, half of the oil consumed in Brazil is used in the transport sector, and from this figure 80% is consumed by road vehicles [1]. The transport sector has caused environmental degradation, not only locally but also globally, and has significantly contributed to the emission of greenhouse gases. Even though there have been significant reductions in the emission of pollutants over the last two decades, internal combustion engine vehicles are still responsible for up to 70% of the total emission of urban pollutants [2]. The emission of such pollutants, like carbon monoxide (CO), sulfur dioxide (SO2), nitrogen oxides (NOx), and carbon dioxide (CO2) which is the major greenhouse gas at the present, represents a major part of the atmospheric pollution. This sector is also responsible for 50% of the global emissions of hydrocarbons [3] and around 30% of the global emissions of carbon dioxide due to energy use [4]. There are many actions intended to control the high levels of pollution caused by vehicles in large cities. Among these actions, the one proposed by the California Air Resources Board (CARB) is the strictest and most rigorous. This proposal required that 2% of the passenger cars and lightest light-duty trucks produced by the auto manufacturers in California were ZEVs (zero emission vehicles) from 1998 [5]. From 2003 this percentage would reach 10% of the total production. This measure greatly increased the existing efforts made by the world's largest and most important car makers to develop vehicles that were technically capable of achieving these requirements. Besides the technologic challenge, the market size and the market share in California were decisive factors to foster research and development in this field. What is the practical importance of these measures? Their importance is that the effective reduction of vehicular emissions demands radical changes in the concepts of motorization and energy supply. Nowadays the only vehicle that fulfills the zero emission requirements is the electric vehicle, when considering the emissions from its propulsion system. The ZEV concept does not consider the emissions associated to other systems different from the vehicle power system; for example the hydrocarbons released by the lubrication system, particulate material from brakes and tires, etc. Neither the emissions originated in previous stages of power generation nor the emissions originated in subsequent stages of material recycling are considered. Since 1990, when CARB announced its resolution to adopt the ZEV commercialization plan, there has been a great mobilization of the vehicle manufacturers concerning the development of clean technologies and the introduction of these technologies in the automobile market. Even though technologic investigations had already been carried out for some years, CARB's initiative contributed to strengthen the general interest and stimulate the acceleration of efforts in the area. The analysts believed that, with this measure, about one million electric vehicles would be in the streets of the United States by 2004. However, in the beginning of 1996, this measure, which would take effect in 1998, was waived. The only requirement that was maintained was the target of 10% of the total Californian fleet to be composed by ZEVs in 2003. Anyhow, many technical advances were attained and the activities on these themes have increased; still, the success of these vehicles deeply depends on the development of on-board technologies for power supply, since the electric vehicles are the only ones which comply with the ZEV attributes at the present time. Among the currently available technologies for electric energy generation, the fuel cells are considered one of the most important alternatives of power supply for electric vehicles. Since the fuel cells are closely related to the hydrogen technology, which is the most appropriate fuel for these cells and provides the best energy performances, this work presents an overview of the evolution of hydrogen-fueled vehicles. Copyright © 2002 Society of Automotive Engineers, Inc.(2001) BEN - Brazilian Energy Balance(1991) National Air Pollutant Emissions Estimates, , Environmental Protection Agency - Office of Air Quality Planning and Standards. EPA-450/-4-91-004, Research Triangle Park, NC, MarchGabel, H.K., Roller, L.H., Trade Liberization, Transportation, and the Environment (1992) The Energy Journal, 12 (1)De Luchi, M.A., (1991) Emissions of Greenhouse Gases from the Use of Transportation Fuels and Electricity, , ANL/ESD/TM-22, Argonne National Laboratory, Argonne, IL, November(1994) International Solar Energy Society, 18 (4). , Decembe

Evaluation of alternative schemes for recording body weights in meat-type quails by using random regression.

Data from 8759 meat-type quails from the UFV1 strain and 9128 from the UFV2 strain were used to assess the possibility of reducing the number of body weight records in genetic evaluations. The evaluated animals were weighed weekly since hatching to the 6th week of life, with up to 7 records of body weight for each bird. The data were evaluated by random regression models, with 9 alternative schemes of data recording, which included 4 records for each scheme and their covariance functions for additive and permanent environmental effects of order 3, fitting 4 intervals for residual variance, and a complete scheme, with 7 records, order of fit 6 for additive and permanent environmental effects and 7 intervals for residual variance. Estimates of heritability for body weight at the 6th week varied from 0.45 to 0.53 for the UFV1 strain and from 0.28 to 0.54 for UFV2 strain. The schemes that had more records in points at the final extreme of the age range showed better estimates, which was likely due to certain properties of polynomial regression that led to biased results in the final extreme of the age range when data are unbalanced. The reduction of the number of body weight records taken during the growth phase is feasible, with little change to breeding value estimates, when 4 body weight records are used in random regression models