Exploring dietary patterns and their association with environmental sustainability and body mass index in children and adolescents: Insights from the National Food, Nutrition and Physical Activity Survey 2015-2016.

OBJECTIVE: To adapt four dietary patterns for children and adolescents, and study their associations with sustainability (greenhouse-gas emissions-GHGE and land use-LU), and health (body mass index-BMI) indicators. RESEARCH METHODS & PROCEDURES: Dietary intake of children (3-9y) and adolescents (10-17y) from the National Food, Nutrition and Physical Activity Survey 2015-2016, Portugal (n = 1153) was assessed through two non-consecutive interviews: one-day food diaries (children), and 24-h recalls (adolescents), using an automated multiple-pass method, including a picture book for portion sizes estimation. Adherence to the Eat-Lancet and World Health Organization (WHO) recommendations, Mediterranean and Atlantic diets were evaluated using adapted versions for pediatrics of the World Index for Sustainability and Health (WISH), Diet Quality Index (DQI), Mediterranean Diet Score (MDS) and Southern-European Atlantic Diet (SEAD), respectively. Diet-related GHGE and LU were estimated using the SHARP-Indicators database. BMI (measured) z-scores were classified according to WHO criteria. A standardized weighted health-sustainability composite index was created (BMI + 0.5*GHGE+0.5*LU). Adjusted linear regression models were computed. RESULTS: WISH, DQI, MDS, and SEAD had weighted mean scores (range) of 50 (0-130), 24 (9-36), 20 (8-32), and 17 (8-32), respectively. All dietary patterns were associated with lower environmental impact, particularly in children, but not with BMI. Only MDS explained both health and sustainability indicators in childhood (composite index: sd.ß = -0·223,95%CI:-0·347,-0·072,R2 = 25.1 %), and adolescence (composite index: sd.ß = -0·159,95%CI:-0·315,-0·003,R2 = 31.3 %). CONCLUSION: The Mediterranean diet was the most related to (higher) environmental sustainability and (lower) BMI. However, in children (not adolescents), the WISH, DQI, and SEAD showed then same associations.

Lyotropic liquid crystalline 2D and 3D mesophases: Advanced materials for multifunctional anticancer nanosystems.

Cancer remains a leading cause of mortality. Despite significant breakthroughs in conventional therapies, treatment is still far from ideal due to high toxicity in normal tissues and therapeutic inefficiency caused by short drug lifetime in the body and resistance mechanisms. Current research moves towards the development of multifunctional nanosystems for delivery of chemotherapeutic drugs, bioactives and/or radionuclides that can be combined with other therapeutic modalities, like gene therapy, or imaging to use in therapeutic screening and diagnosis. The preparation and characterization of Lyotropic Liquid Crystalline (LLC) mesophases self-assembled as 2D and 3D structures are addressed, with an emphasis on the unique properties of these nanoassemblies. A comprehensive review of LLC nanoassemblies is also presented, highlighting the most recent advances and their outstanding advantages as drug delivery systems, including tailoring strategies that can be used to overcome cancer challenges. Therapeutic agents loaded in LLC nanoassemblies offer qualitative and quantitative enhancements that are superior to conventional chemotherapy, particularly in terms of preferential accumulation at tumor sites and promoting enhanced cancer cell uptake, lowering tumor volume and weight, improving survival rates, and increasing the cytotoxicity of their loaded therapeutic agents. In terms of quantitative anticancer efficacy, loaded LLC nanoassemblies reduced the IC50 values from 1.4-fold against lung cancer cells to 125-fold against ovarian cancer cells.

Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.

BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.

Natural Compounds: Co-Delivery Strategies with Chemotherapeutic Agents or Nucleic Acids Using Lipid-Based Nanocarriers.

Cancer is one of the leading causes of death, and latest predictions indicate that cancer- related deaths will increase over the next few decades. Despite significant advances in conventional therapies, treatments remain far from ideal due to limitations such as lack of selectivity, non-specific distribution, and multidrug resistance. Current research is focusing on the development of several strategies to improve the efficiency of chemotherapeutic agents and, as a result, overcome the challenges associated with conventional therapies. In this regard, combined therapy with natural compounds and other therapeutic agents, such as chemotherapeutics or nucleic acids, has recently emerged as a new strategy for tackling the drawbacks of conventional therapies. Taking this strategy into consideration, the co-delivery of the above-mentioned agents in lipid-based nanocarriers provides some advantages by improving the potential of the therapeutic agents carried. In this review, we present an analysis of the synergistic anticancer outcomes resulting from the combination of natural compounds and chemotherapeutics or nucleic acids. We also emphasize the importance of these co-delivery strategies when reducing multidrug resistance and adverse toxic effects. Furthermore, the review delves into the challenges and opportunities surrounding the application of these co-delivery strategies towards tangible clinical translation for cancer treatment.

pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance.

Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy.

Activation of an actin signaling pathway in pre-malignant mammary epithelial cells by P-cadherin is essential for transformation.

Alterations in the expression or function of cell adhesion molecules have been implicated in all steps of tumor progression. Among those, P-cadherin is highly enriched in basal-like breast carcinomas, playing a central role in cancer cell self-renewal, collective cell migration and invasion. To establish a clinically relevant platform for functional exploration of P-cadherin effectors in vivo, we generated a humanized P-cadherin Drosophila model. We report that actin nucleators, Mrtf and Srf, are main P-cadherin effectors in fly. We validated these findings in a human mammary epithelial cell line with conditional activation of the SRC oncogene. We show that, prior to promoting malignant phenotypes, SRC induces a transient increase in P-cadherin expression, which correlates with MRTF-A accumulation, its nuclear translocation and the upregulation of SRF target genes. Moreover, knocking down P-cadherin, or preventing F-actin polymerization, impairs SRF transcriptional activity. Furthermore, blocking MRTF-A nuclear translocation hampers proliferation, self-renewal and invasion. Thus, in addition to sustaining malignant phenotypes, P-cadherin can also play a major role in the early stages of breast carcinogenesis by promoting a transient boost of MRTF-A-SRF signaling through actin regulation.

Surface-modified lipid nanocarriers for crossing the blood-brain barrier (BBB): A current overview of active targeting in brain diseases.

The blood-brain barrier (BBB) restricts the access of therapeutic agents to the brain, complicating the treatment of neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), glioma, etc. To overcome this limitation and improve drug delivery to the central nervous system (CNS), the potential of nanocarriers, including lipid-based nanosystems, has been explored. Through active targeting, the surface of the nanocarriers can be modified with ligands that interact with the BBB, enhancing their uptake and penetration across the brain endothelium by different physiological mechanisms, such as receptor- or transporter-mediated transcytosis. This review seeks to provide an overview of active targeting in brain delivery, while highlighting the potential of functionalized lipid nanocarriers to treat brain diseases. Therefore, in the first sections, we discuss the importance of active targeting in CNS drug delivery, present the different ligands commonly used for functionalization, as well as summarize the state of the art of the most recent and relevant studies of surface-modified lipid nanosystems developed for neurological disorders. Lastly, challenges hindering clinical translation are discussed, and critical insights and future perspectives outlined. Although some limitations have been identified, it is expected that in the upcoming years these nanosystems will be an established approach.

Role of syndecan-4 in breast cancer pathophysiology.

Expression of the cell surface heparan sulfate proteoglycan syndecan-4 is dysregulated in breast cancer, the most frequent malignancy in women. High expression of syndecan-4 correlates with a worse survival in the subgroup of estrogen receptor negative and estrogen/progesterone-receptor negative patients. Aberrant expression of syndecan-4 in breast cancer involves both transcriptional and posttranscriptional mechanisms, including estrogen- and growth factor-dependent regulation, mutations in GAPVD1, NUP153, PDE4DIP, and RREB1, as well as targeting by microRNAs. At the functional level, syndecan-4 plays an important role in various stages of breast cancer progression by interacting with ligands as diverse as plasma proteins, extracellular matrix proteins, growth factors, and surface receptors, as well as members of the integrin family. Mechanisms including integrin recycling, ectodomain shedding, and crosstalk with other syndecans expand the repertoire of syndecan-4 function. Through these interactions, syndecan-4 regulates cellular processes such as adhesion, migration, and invasion. Additional possible functions of syndecan-4 in cells of the microenvironment contribute to the complexity of its pathophysiology. Notably, syndecan-4 expression is modulated by drugs used in breast cancer treatment, such as trastuzumab and zoledronate. Overall, these findings mark syndecan-4 as a novel pathogenesis factor and promising target for therapeutic interventions in breast cancer.

Olive oil consumption and all-cause, cardiovascular and cancer mortality in an adult mediterranean population in Spain.

Objective: We assessed the association between usual olive oil consumption (OOC) and all-cause, cardiovascular (CVD) and cancer mortality in an adult population in Spain. Materials and methods: OOC was evaluated at baseline in 1,567 participants aged 20 years and older from the Valencia Nutrition Study in Spain using validated food frequency questionnaires. During an 18-year follow-up period, 317 died, 115 due to CVD and 82 due to cancer. Cox regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95%CI). Results: After adjusting for demographic and lifestyle factors, the OOC was associated with a lower risk of all-cause, CVD and cancer mortality. Compared to the less than once per month consumption, the consumption of up to one tablespoon per day was associated with a 9% lower risk of all-cause mortality (HR: 0.91; 95%CI: 0.68-1.22) and the consumption of 2 or more tablespoons with a 31% lower risk of all-cause mortality (HR: 0.69; 95%CI: 0.50-0.93; p-trend = 0.011). The consumption of 2 or more tablespoons per day was also associated with lower risk of mortality for CVD (HR: 0.54; 95%CI: 0.32-0.91; p-trend = 0.018) and cancer (HR: 0.49, 95%CI: 0.26-0.94; p-trend = 0.019). Conclusion: Higher olive oil consumption was associated with lower long-term risk of all-cause, CVD and cancer mortality in an adult Mediterranean population. The maximum benefit was observed for the consumption of two or more tablespoons per day.

Preparation, cytotoxic activity and DNA interaction studies of new platinum(II) complexes with 1,10-phenanthroline and 5-alkyl-1,3,4-oxadiazol-2(3H)-thione derivatives.

This work describes the synthesis, characterization and in vitro anticancer activity of two platinum(II) complexes of the type [Pt(L1)2(1,10-phen)] 1 and [Pt(L2)2(1,10-phen)] 2, where L1 = 5-heptyl-1,3,4-oxadiazole-2-(3H)-thione, L2 = 5-nonyl-1,3,4-oxadiazole-2-(3H)-thione and 1,10-phen = 1,10-phenanthroline. As to the structure of these complexes, the X-ray structural analysis of 1 indicates that the geometry around the platinum(II) ion is distorted square-planar, where two 5-alkyl-1,3,4-oxadiazol-2-thione derivatives coordinate a platinum(II) ion through the sulfur atom. A chelating bidentate phenanthroline molecule completes the coordination sphere. We tested these complexes in two breast cancer cell lines, namely, MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). In both cells, the most lipophilic platinum compound, complex 2, was more active than cisplatin, one of the most widely used anticancer drugs nowadays. DNA binding studies indicated that such complexes are able to bind to ct-DNA with Kb values of 104 M-1. According to data from dichroism circular and fluorescence spectroscopy, these complexes appear to bind to the DNA in a non-intercalative, probably via minor groove. Molecular docking followed by semiempirical simulations indicated that these complexes showed favorable interactions with the minor groove of the double helix of ct-DNA in an A-T rich region. Thereafter, flow cytometry analysis showed that complex 2 induced apoptosis and necrosis in MCF-7 cells.

Mitochondrial and redox modifications in early stages of Huntington's disease.

Deficits in mitochondrial function and redox deregulation have been attributed to Huntington's disease (HD), a genetic neurodegenerative disorder largely affecting the striatum. However, whether these changes occur in early stages of the disease and can be detected in vivo is still unclear. In the present study, we analysed changes in mitochondrial function and production of reactive oxygen species (ROS) at early stages and with disease progression. Studies were performed in vivo in human brain by PET using [64Cu]-ATSM and ex vivo in human skin fibroblasts of premanifest and prodromal (Pre-M) and manifest HD carriers. In vivo brain [64Cu]-ATSM PET in YAC128 transgenic mouse and striatal and cortical isolated mitochondria were assessed at presymptomatic (3 month-old, mo) and symptomatic (6-12 mo) stages. Pre-M HD carriers exhibited enhanced whole-brain (with exception of caudate) [64Cu]-ATSM labelling, correlating with CAG repeat number. Fibroblasts from Pre-M showed enhanced basal and maximal respiration, proton leak and increased hydrogen peroxide (H2O2) levels, later progressing in manifest HD. Mitochondria from fibroblasts of Pre-M HD carriers also showed reduced circularity, while higher number of mitochondrial DNA copies correlated with maximal respiratory capacity. In vivo animal PET analysis showed increased accumulation of [64Cu]-ATSM in YAC128 mouse striatum. YAC128 mouse (at 3 months) striatal isolated mitochondria exhibited a rise in basal and maximal mitochondrial respiration and in ATP production, and increased complex II and III activities. YAC128 mouse striatal mitochondria also showed enhanced mitochondrial H2O2 levels and circularity, revealed by brain ultrastructure analysis, and defects in Ca2+ handling, supporting increased striatal susceptibility. Data demonstrate both human and mouse mitochondrial overactivity and altered morphology at early HD stages, facilitating redox unbalance, the latter progressing with manifest disease.

Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease.

Host immune responses contribute to dengue's pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected with dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac2-26 for analysis. In addition, the effect of Ac2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease.

Risk characterization of dietary acrylamide exposure and associated factors in the Portuguese population.

Acrylamide exposure, mainly resulting from food cooking and processing, has been associated with a higher risk of health problems, due to genotoxic effects. This study aims to estimate acrylamide dietary exposure of the Portuguese population and its associated factors. Dietary data collected through 2 non-consecutive 24 hour recalls or food diaries from a representative sample of the Portuguese population from the National Food, Nutrition and Physical Activity Survey was used (n = 5811; 3-84 years). Occurrence data of acrylamide in food were obtained from EFSA. The margins of exposure (MOE) were calculated for peripheral neuropathy and neoplastic effects. The association between acrylamide and socio-demographic characteristics was estimated through linear regression models. For the total population, the estimated median daily dietary exposure per body weight to acrylamide was 0.38 µg/kg/day, ranging from 0.14 to 0.88 µg/kg/day for the 5th and 95th percentile, respectively. Children aged between 1-2 years had the highest acrylamide exposure (median 0.75 µg/kg/day, 95th percentile 1.41 µg/kg/day). For the peripheral neuropathy and neoplastic effects, the median MOE estimated was 1140 and 451, respectively. Men compared to women had a higher acrylamide dietary exposure, as well as smokers compared to non-smokers. Elderly and less educated individuals were inversely associated with acrylamide exposure. 'Bread and rusks' (24.2%) were the main source of acrylamide, followed by 'coffee' (21.3%). The current dietary exposure to acrylamide in the Portuguese population is of concern mainly regarding neoplastic effects. Our results point to the need to reduce exposure to acrylamide, especially in men, young children, higher educated individuals and smokers.

Is the association between dietary patterns and cognition mediated by children's adiposity? A longitudinal approach in Generation XXI birth cohort.

BACKGROUND/AIMS: There is a consistent body of evidence on the association between single nutrients and cognition, but the role of a healthful dietary pattern on cognition in children has been seldomly studied. This study aims to assess the association between dietary patterns at 4 years (y) and cognitive abilities at 10-13y and examine whether adiposity mediated these associations. METHODS: This study used data from a sub-sample of the population-based birth cohort Generation XXI, with complete information on diet and cognition (n = 3575). At 4y, data on dietary intake was collected by a validated food frequency questionnaire and dietary patterns were derived by latent class analysis, namely Energy-dense food (EDF) pattern, Snacking pattern and Healthier pattern (Reference). At 10-13y, the Portuguese Version of the Wechsler Intelligence Scale for Children®-Third Edition was administered by trained psychologists and age-adjusted composite scores were computed: a Full-Scale Intelligence Quotient (IQ), plus a Verbal IQ, Performance IQ and Processing Speed IQ. Age- and sex-specific body mass index (BMI) z-scores, body fat percentage from bioimpedance, and waist-to-weight ratio and waist-to-hip ratio were used as measures of adiposity. Regression coefficients and 95% confidence intervals (CI) were computed using linear regression models (adjusted for maternal age and education, pre-pregnancy BMI, smoking and alcohol intake during pregnancy, child's sex, birthweight, exclusive breastfeeding duration and having siblings at 4y). Mediation analysis was conducted using path analysis. RESULTS: After adjustment, children classified in the EDF or a Snacking patterns at 4y were more likely to have lower scores on total IQ (ß = -0.116; 95%CI:-0.192,-0.039 and ß = -0.148; 95%CI -0.252,-0.044, respectively), Verbal IQ (ß = -0.104; 95%CI -0.177, -0.031 and ß = -0.163; 95%CI -0.262,-0.064, respectively) and Performance IQ (ß = -0.116 95%CI -0.193,-0.040 and ß = -0.147; 95%CI -0.250,-0.042, respectively) at 10-13y, when compared to those classified in the Healthier pattern. None of the adiposity measures seemed to explain the associations between dietary patterns and IQ. CONCLUSION: This study supports that early unhealthy dietary patterns were associated with lower child's cognitive ability, but this effect did not seem to be mediated by adiposity.

Interaction effects of socio-economic position in the association between eating location and diet quality in Portuguese children and adolescents: results from the National Food, Nutrition and Physical Activity Survey 2015-2016.

This study aims to evaluate the interaction effect of socio-economic environment (SEE) in the relationship between the eating location (EL) and diet quality, in children and adolescents. Data included Portuguese children and adolescents (3-17 years) from a National Dietary Survey Sample (IAN-AF 2015/2016, n 987). Dietary intake was obtained by 2-d food diaries (children) or 2-24-h-recall (adolescents). Participants were classified into four groups of EL: 'Home', 'Other homes', 'School' and 'Restaurants'. Diet quality was measured as a higher adherence to a healthy eating pattern. A previous developed socio-economic classification was used, and participants were grouped as belonging to a low socio-economic environment (LSE) or middle-high socio-economic environment (MHSE). Linear regression models were used to evaluate the association between EL and diet quality, stratified by the SEE. A statistically significant interaction effect was found (P < 0·01) for the SEE in the association between EL and diet quality. After adjustment for potential confounders, in LSE, participants belonging to 'Other homes' (ß = -2·07; 95 % CI:-3·70, -0·44) and 'Restaurants' (ß = -3·31; 95 % CI: -5·08, -1·54) had lower scores in the diet quality score, comparing to 'Home'. In MHSE, comparing with 'Home', 'Restaurants' showed lower diet quality (ß = -1·56; 95 % CI:-2·65, -0·48), while the 'School' had better diet quality (ß = 0·90; 95 % CI: 0·16, 1·64). The SEE influences the association between EL and diet quality and, belonging to more disadvantaged SEE, might represent a higher risk of unhealthy eating habits when eating out-of-home.

From genes to ecosystems: a synthesis of amphibian biodiversity research in Brazil / De genes a ecossistemas: uma síntese da pesquisa em biodiversidade de anfíbios no Brasil

Abstract Here, we summarize examples of significant advances in amphibian research supported by the São Paulo Research Foundation (FAPESP), focusing on recent discoveries in the fields of community ecology, habitat change, infection diseases, and multipurpose DNA sequencing. We demonstrated that FAPESP has been fundamental not only by directly funding research projects and scholarships, but also through its science training policy, fostering international collaborations with world-class research institutions, improving and consolidating new lines of research that often depended on a synergetic combination of different knowledge and complex tools. We emphasized that future studies will continue to focus on basic questions, such as description of new species, as well as taxonomic and systematic corrections. Furthermore, we also expect that there will be a strong integration among different disciplines using novel bioinformatics tools and modeling approaches, such as machine learning. These new approaches will be critical to further develop our understanding of foundational questions of amphibian life-history trait variation, disease transmission, community assembly, biogeography, and population forecasts under different global change scenarios such as agricultural expansion, agrochemical use, habitat loss, and climate change.

Resumo No presente estudo apresentamos exemplos de avanços significativos nas pesquisas com anfíbios financiadas pela Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), focando em descobertas recentes nos campos de ecologia de comunidades, modificação do habitat, doenças infecciosas e o sequenciamento de DNA com múltiplos propósitos. Demonstramos que a FAPESP tem sido fundamental não somente pelo financiamento direto de projetos de pesquisa e bolsas de estudo, mas também através de sua política de formação científica, fomentando colaborações internacionais com instituições de pesquisa de excelência mundial, melhorando e consolidando novas linhas de pesquisa que frequentemente dependem da combinação sinérgica entre diferentes linhas de conhecimento e ferramentas complexas. Enfatizamos que futuros estudos continuem com foco em questões básicas, como a descrição de novas espécies, bem como correções taxonômicas e sistemáticas. Além disso, esperamos uma forte integração entre diferentes disciplinas usando novas ferramentas de bioinformática e abordagens de modelagem, como o aprendizado de máquina. Essas novas abordagens serão críticas para desenvolver ainda mais nossa compreensão a respeito de questões fundamentais sobre as características da história de vida dos anfíbios, transmissão de doenças, estrutura de comunidades, biogeografia e previsões populacionais em diferentes cenários de mudanças globais, como a expansão da agricultura, uso de agrotóxicos, perda de habitat e mudanças climáticas.

Novel Nile Blue Analogue Stains Yeast Vacuolar Membrane, Endoplasmic Reticulum, and Lipid Droplets, Inducing Cell Death through Vacuole Membrane Permeabilization.

Phenoxazine derivatives such as Nile Blue analogues are assumed to be increasingly relevant in cell biology due to their fluorescence staining capabilities and antifungal and anticancer activities. However, the mechanisms underlying their effects remain poorly elucidated. Using S. cerevisiae as a eukaryotic model, we found that BaP1, a novel 5- and 9-N-substituted benzo[a]phenoxazine synthesized in our laboratory, when used in low concentrations, accumulates and stains the vacuolar membrane and the endoplasmic reticulum. In contrast, at higher concentrations, BaP1 stains lipid droplets and induces a regulated cell death process mediated by vacuolar membrane permeabilization. BaP1 also induced mitochondrial fragmentation and depolarization but did not lead to ROS accumulation, changes in intracellular Ca2+, or loss of plasma membrane integrity. Additionally, our results show that the cell death process is dependent on the vacuolar protease Pep4p and that the vacuole permeabilization results in its translocation from the vacuole to the cytosol. In addition, although nucleic acids are commonly described as targets of benzo[a]phenoxazines, we did not find any alterations at the DNA level. Our observations highlight BaP1 as a promising molecule for pharmacological application, using vacuole membrane permeabilization as a targeted approach.

Associated factors to the consumption of ultra-processed foods and its relation with dietary sources in Portugal.

Ultra-processed foods (UPFs) are common worldwide and associated with poorer health outcomes. This work aimed to explore the UPF consumption associated factors and its main dietary sources, by sex, in Portugal. Participants from the National Food, Nutrition and Physical Activity Survey (IAN-AF) 2015-2016, aged 3-84 years, were included (n 5005). Dietary intake was assessed through two 1-day food diaries/24 h recalls. UPFs were identified using the NOVA classification. Associations were evaluated through linear regression models. Median UPF consumption was 257 g/d (10⋅6 % of total quantity; 23⋅8 % of total energy). Adolescents were those with higher consumption (490 g/d). Compared to adults, younger ages were positively associated with UPF consumption (e.g. adolescents (-females: 192, 95 % confidence interval (CI): 135, 249; -males: 327, 95 % CI: 277, 377)). A lower educational level was associated with lower UPF consumption (-females: -63; 95 % CI: -91, -34; -males: -68; 95 % CI: -124, -12). Also, a lower UPF consumption was observed in married males/couples compared to singles (: -48, 95 % CI: -96, -1). Furthermore, female current/former smokers were associated with a higher UPF consumption v. never smokers (: 79, 95 % CI: 41, 118; : 42, 95 % CI: 8, 75, respectively). Main UPF sources were yoghurts, soft drinks and cold meats/sausages differing strongly by sex, age and education level. Yoghurts containing additives were the main contributors to the UPF consumption in children and adult females from all education (~20 %). Soft drinks were leaders in adolescents (females: 26⋅0 %; males: 31⋅6 %) and young male adults (24⋅4 %). Cold meats/sausages stood out among low-educated males (20⋅5 %). Males, younger age groups, higher education, children with less-educated parents, married/couple males and smoking females were positively associated with UPF consumption.

Omega-3- and Resveratrol-Loaded Lipid Nanosystems for Potential Use as Topical Formulations in Autoimmune, Inflammatory, and Cancerous Skin Diseases.

Resveratrol (RSV) and omega 3 (ω3), because of their biological favorable properties, have become subjects of interest for researchers in dermocosmetic and pharmaceutical industries; however, these bioactives present technological limitations that hinder their effective delivery to the target skin layer. To overcome the stability and skin permeation limitations of free bioactives, this work proposes a combined strategy involving two different lipid nanosystems (liposomes and lipid nanoparticles) that include ω3 in their lipid matrix. Additionaly, RSV is only encapsulated in liposomes that provid an adequate amphiphilic environment. Each formulation is thoroughly characterized regarding their physical-chemical properties. Subsequently, the therapeutic performance of the lipid nanosystems is evaluated based on their protective roles against lipid peroxidation, as well as inhibition of cicloxygenase (COX) and nitric oxid (NO) production in the RWA264.7 cell line. Finally, the lipid nanosystems are incorporated in hydrogel to allow their topical administration, then rheology, occlusion, and RSV release-diffusion assays are performed. Lipid nanoparticles provide occlusive effects at the skin surface. Liposomes provide sustained RSV release and their flexibility conferred by edge activator components enhances RSV diffusion, which is required to reach NO production cells and COX cell membrane enzymes. Overall, the inclusion of both lipid nanosystems in the same semisolid base constitutes a promising strategy for autoimmune, inflammatory, and cancerous skin diseases.

microRNA-140-3p modulates invasiveness, motility, and extracellular matrix adhesion of breast cancer cells by targeting syndecan-4.

Syndecan-4, a predicted target of the microRNA miR-140-3p, plays an important role in multiple steps of tumor progression and is the second most abundant heparan sulfate proteoglycan produced by breast carcinoma cell lines. To investigate the potential functional relationship of miR-140-3p and syndecan-4, MDA-MB-231, SKBR3, and MCF-7 breast cancer (BC) cells were transiently transfected with pre-miR-140-3p, syndecan-4 small interfering RNAJ, or control reagents, respectively. Altered cell behavior was monitored by adhesion, migration, and invasion chamber assays. Moreover, the prognostic value of syndecan-4 was assessed by Kaplan-Maier Plotter analysis of gene expression data from tumor samples of 4929 patients. High expression of syndecan-4 was associated with better relapse-free survival in the whole collective of BC patients, but correlated with a worse survival in the subgroup of estrogen receptor negative and estrogen/progesterone-receptor negative patients. miR-140-3p expression was associated with improved survival irrespective of hormone receptor status. miR-140-3p overexpression induced posttranscriptional downregulation of syndecan-4, as demonstrated by quantitative real-time PCR (qPCR), flow cytometry, and luciferase assays, resulting in decreased BC cell migration and matrigel invasiveness. Furthermore, miR-140-3p overexpression and syndecan-4 silencing increased the adhesion of BC to fibronectin and laminin. qPCR analysis demonstrated that syndecan-4 silencing leads to altered gene expression of adhesion-related molecules, such as fibronectin and focal adhesion kinase, as well as in the gene expression of the proinvasive factors matrix metalloproteinase 2 and heparanase (also known as HPSE). We conclude that syndecan-4 is a novel target of miR-140-3p that regulates BC cell invasiveness and cell-matrix interactions in the tumor microenvironment.