Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor.

Glucocorticoids (GCs) are hormones involved in circadian adaptation and stress response, and it is also noteworthy that these steroidal molecules present potent anti-inflammatory action through GC receptors (GR). Upon ligand-mediated activation, GR translocates to the nucleus, and regulates gene expression related to metabolism, acute-phase response and innate immune response. GR field of research has evolved considerably in the last decades, providing varied mechanisms that contributed to the understanding of transcriptional regulation and also impacted drug design for treating inflammatory diseases. Liquid-liquid phase separation (LLPS) in cellular processes represents a recent topic in biology that conceptualizes membraneless organelles and microenvironments that promote, or inhibit, chemical reactions and interactions of protein or nucleic acids. The formation of these molecular condensates has been implicated in gene expression control, and recent evidence shows that GR and other steroid receptors can nucleate phase separation (PS). Here we briefly review the varied mechanisms of transcriptional control by GR, which are largely studied in the context of inflammation, and further present how PS can be involved in the control of gene expression. Lastly, we consider how the reported advances on LLPS during transcription control, specially for steroid hormone receptors, could impact the different modalities of GR action on gene expression, adding a new plausible molecular event in glucocorticoid signal transduction.

The Anti-Dengue Virus Peptide DV2 Inhibits Zika Virus Both In Vitro and In Vivo.

The C-terminal portion of the E protein, known as stem, is conserved among flaviviruses and is an important target to peptide-based antiviral strategies. Since the dengue (DENV) and Zika (ZIKV) viruses share sequences in the stem region, in this study we evaluated the cross-inhibition of ZIKV by the stem-based DV2 peptide (419-447), which was previously described to inhibit all DENV serotypes. Thus, the anti-ZIKV effects induced by treatments with the DV2 peptide were tested in both in vitro and in vivo conditions. Molecular modeling approaches have demonstrated that the DV2 peptide interacts with amino acid residues exposed on the surface of pre- and postfusion forms of the ZIKA envelope (E) protein. The peptide did not have any significant cytotoxic effects on eukaryotic cells but efficiently inhibited ZIKV infectivity in cultivated Vero cells. In addition, the DV2 peptide reduced morbidity and mortality in mice subjected to lethal challenges with a ZIKV strain isolated in Brazil. Taken together, the present results support the therapeutic potential of the DV2 peptide against ZIKV infections and open perspectives for the development and clinical testing of anti-flavivirus treatments based on synthetic stem-based peptides.

The biological role of charge distribution in linear antimicrobial peptides.

INTRODUCTION: Antimicrobial peptides (AMP) have received particular attention due to their capacity to kill bacteria. Although much is known about them, peptides are currently being further researched. A large number of AMPs have been discovered, but only a few have been approved for topical use, due to their promiscuity and other challenges, which need to be overcome. AREAS COVERED: AMPs are diverse in structure. Consequently, they have varied action mechanisms when targeting microorganisms or eukaryotic cells. Herein, the authors focus on linear peptides, particularly those that are alpha-helical structured, and examine how their charge distribution and hydrophobic amino acids could modulate their biological activity. EXPERT OPINION: The world currently needs urgent solutions to the infective problems caused by resistant pathogens. In order to start the race for antimicrobial development from the charge distribution viewpoint, bioinformatic tools will be necessary. Currently, there is no software available that allows to discriminate charge distribution in AMPs and predicts the biological effects of this event. Furthermore, there is no software available that predicts the side-chain length of residues and its role in biological functions. More specialized software is necessary.

Fosfomycin and nitrofurantoin: classic antibiotics and perspectives.

Antibiotics are essential molecules for the treatment and prophylaxis of many infectious diseases. However, drugs that combat microbial infections can become a human health threat due to their high and often indiscriminate consumption, considered one of the factors of antimicrobial resistance (AMR) emergence. The AMR crisis, the decrease in new drug development by the pharmaceutical industry, and reduced economic incentives for research have all reduced the options for treating infections, and new strategies are necessary, including the return of some traditional but "forgotten" antibiotics. However, prescriptions for these older drugs including nitrofurantoin and oral fosfomycin, have been based on the results of pioneer studies, and the limited knowledge generated 50-70 years ago may not be enough. To avoid harming patients and further increasing multidrug resistance, systematic evaluation is required, mainly for the drugs prescribed for community-acquired infections, such as urinary tract infections (UTI). Therefore, this review has the objective of reporting the use of two classic drugs from the nitrofuran and phosphonic acid classes for UTI control nowadays. Furthermore, we also explore new approaches used for these antibiotics, including new combination regimes for spectral amplification, and the prospects for reducing bacterial resistance in the fight against bacteria responsible for UTI.

Physical Activity Level, Anthropometric and Cardiovascular Profile Among Students in Sergipe State Attending Public Schools

Abstract Background Cardiovascular diseases are the leading cause of mortality among adults. Evidence has shown that sedentary behaviors are the main preventable outcome, however, many sedentary children also become sedentary adults. Therefore, identifying potential risk factors as early as possible contributes to therapeutic success. Objective To achieve an anthropometric and cardiovascular mapping of school-age students from Sergipe State, Brazil. Methods A school-based cross-sectional study with a representative sample from public schools in the state of Sergipe (n= 4700). Anthropometric and blood pressure measurements were performed, and the Global School-based Student Health Survey was used to assess the physical activity level. An independent samples t-test was performed for all comparisons, and significance was established at 5% (p<0.05). Results Despite showing mean blood pressure values within reasonable limits (SBP = 114.1±12.4 mm Hg and DBP = 66.3±8.1 mm Hg), school-age students did not comply with global recommendations for health promotion. It was also observed a high rate of low body weight (42.6%), suggesting dietary compromises, which can interfere with the development of this population. In addition, only 7.3% of students met the minimum physical activity criteria proposed for maintaining their health status. Conclusion The findings of the present study emphasize the importance of maintaining Physical Education classes as an essential curricular component, since they provide several health benefits and ensure that this population reaches the minimum daily recommendations, preventing diseases in adult life. (Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0)

Brain Innate Immune Response in Diet-Induced Obesity as a Paradigm for Metabolic Influence on Inflammatory Signaling.

Obesity is a predisposing factor for numerous morbidities, including those affecting the central nervous system. Hypothalamic inflammation is a hallmark of obesity and is believed to participate in the onset and progression of the obese phenotype, by promoting changes in neuronal functions involved in the control of metabolism. The activation of brain immune cells in the hypothalamus, which are represented by microglia and brain macrophages, is associated with obesity and has been the focus of intense research. Despite the significant body of knowledge gathered on this topic, obesity-induced metabolic changes in brain cells involved in innate immune responses are still poorly characterized due, at least in part, to limitations in the existing experimental methods. Since the metabolic state influences immune responses of microglia and other myeloid cells, the understanding and characterization of the effects of cellular metabolism on the functions of these cells, and their impact on brain integrity, are crucial for the development of efficient therapeutic interventions for individuals exposed to a long-term high fat diet (HFD). Here we review and speculate on the cellular basis that may underlie the observed changes in the reactivity and metabolism of the innate immune cells of the brain in diet-induced obesity (DIO), and discuss important points that deserve further investigation.

Quantitative expression of microRNAs in Brassica oleracea infected with Xanthomonas campestris pv. campestris.

Brassica oleracea var. capitata (cabbage) is an economically important crop affected by black rot disease caused by Xanthomonas campestris pv. campestris (Xcc). MicroRNAs (miRNAs) play an important role in plant defense modulation and therefore the analysis of these molecules can help better understand plant-pathogen interactions. In this study, we report the differential expression of four miRNAs that seem to participate in the plant response to Xcc infection. Northern Blot and RT-qPCR techniques were used to measure miRNA expression in resistant (União) and susceptible (Kenzan) cultivars. From 6 miRNAs analyzed, 4 were detected and differentially expressed, showing a down- and upregulated expression profile in susceptible and resistant cultivars, respectively. These results suggest that miR156, miR167, miR169, and miR390 could play a role in B. oleracea resistance enhancement against Xcc and could be explored as potential resistance markers in B. oleracea-Xcc interaction.

Association between insufficient level of physical activity and multiple health risk behaviors in adolescents

Aim: To verify the association between insufficient level of physical activity and multiple health risk behaviors (HRB) in adolescents. Methods: This is an epidemiological study with cross-sectional design carried out in 2016 with 3,617 adolescents aged 14-19 years and enrolled in the public-school system of Sergipe, northeast Brazil. Data were collected using the Global School-based Student Health Survey (GSHS/WHO). The insufficient level of physical activity was defined as not achieving at least 60 minutes of moderate to vigorous physical activity for 5 days a week. The HRB analyzed were smoking, alcohol consumption, low fruit consumption and exposure to sedentary behavior. The analysis of prevalence odds ratio was used to identify the association between insufficient level of physical activity and HRB, as well as unadjusted and adjusted binary logistic regression for the association between socioeconomic and demographic variables. Results: The prevalence of insufficient level of physical activity was 83.3%. There was association between physical inactivity and low fruit consumption and alcohol consumption (p<0.001). Insufficient level of physical activity was also associated with female sex (OR=1.90, 95% CI, 1.56-2.32), family income of up to 2 minimum wages (OR=1.57, 95% CI, 1.17-2.11), maternal schooling less than 8 years (OR=1.55, 95% CI, 1.28-1.86) and exposure to two different HRB at the same time (OR=1.76, 95% CI, 1.27-2.45). Conclusion: The prevalence of insufficient level of physical activity is high and was associated with multiple HRBs in this understudied population. These findings may support interventions focusing on the cluster of risk behaviors in youth.(AU)