Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements

A considerable number of genes that code for AU-rich mRNAs including cytokines, growth factors, transcriptional factors, and certain receptors are involved in both chronic inflammation and cancer. Overexpression of these genes is affected by aberrations or by prolonged activation of several signaling pathways. AU-rich elements (ARE) are important cis-acting short sequences in the 3′UTR that mediate recognition of an array of RNA-binding proteins and affect mRNA stability and translation. This review addresses the cellular and molecular mechanisms that are common between inflammation and cancer and that also govern ARE-mediated post-transcriptional control. The first part examines the role of the ARE-genes in inflammation and cancer and sequence characteristics of AU-rich elements. The second part addresses the common signaling pathways in inflammation and cancer that regulate the ARE-mediated pathways and how their deregulations affect ARE-gene regulation and disease outcome

CHIRAL QUADRIDENTATE LIGANDS BASED ON AMINO-ACIDS - TEMPLATE SYNTHESES AND PROPERTIES OF THE FREE LIGANDS AND THEIR TRANSITION-METAL COMPLEXES

The copper(II)-directed condensation of amino acids with formaldehyde and nitroethane has produced new open-chain quadridentate ligands stereoselectively and in generally high yield. The free ligands with pendant amine substituents may be isolated by zinc reduction of the copper(II) complexes. The reactions studied employed optically pure L-amino acids with non-co-ordinating side chains, racemic amino acids with non-co-ordinating side chains, amino acid mixtures and beta-amino acids. The quadri- and quinquedentate ligands form very stable complexes with transition-metal ions, with their copper(II) complexes being generally stable down to pH almost-equal-to 1. The isolation and spectroscopic properties (UV/VIS, IR, NMR and EPR) of cobalt(III) and copper(II) complexes of some of the amino acid-based ligands are reported. Condensation of racemic and mixed amino acids led to one out of three possible quadridentate ligands, and this stereoselectivity is interpreted based on a model involving the co-ordination of an organic nitro group. This mechanism is supported by qualitative molecular mechanics calculations. The crystal structures of the condensation products with beta-alanine, ([Cu(mnp-beta-ala)].5H2O (mnp-beta-ala = 6-methyl-6-nitro-4,8-diazaundecanedioate), and the Zn-HCI reduction product of the condensation with glycine [Cu(Hampgly)Cl].2H2O (ampgly = 5-amino-5-methyl-3,7-diazanonanedioate), have been determined. In the former structure the Cu(II) is in a distorted trigonal-bipyramidal environment with the fifth site being a co-ordinated carboxylate oxygen from an adjacent molecule, while in the latter Cu(II) has a square-pyramidal co-ordination with an apical chloride ligand

Cardiovascular risk associated with high sodium-containing drugs: A systematic review.

Excess dietary sodium is associated with increased blood pressure (BP). Some drugs are associated with high sodium intake (in particular effervescent tablets), but the cardiovascular risk associated with such high sodium-containing drugs (HSCD) is largely underevaluated.To summarize the evidence for a potential cardiovascular risk associated with exposure to HSCD, and to highlight possible risk factors associated with this iatrogenic issue; in general and/or specific populations.We conducted a systematic review, by searching electronic databases including MEDLINE, EMBASE, Web of Science, CENTRAL and grey literature between 1960 and 2015. We included studies that reported modification of cardiovascular parameters or incidence/prevalence of cardiovascular outcomes, between a group of subjects exposed to HSCD relative to a non-exposed group. The threshold used to identify HSCD was 391 mg/day. We did not consider studies evaluating exposure to sodium as an active ingredient or those focusing on dialysis solutions or enteral/parenteral nutrition. Study quality was assessed using the EPHPP tool.A total of eight studies met our inclusion criteria. Four reported results for short-term exposure to HSCD (≤ 7 days) on BP fluctuations. One study reported an elevation of BP (associated sodium intake: 1,656 mg/day). Four studies evaluated a long-term exposure (≥ 2 years or discontinuation of a chronic treatment). Two studies reported iatrogenic risk. For these studies, drug associated sodium intake was high (> 1,500 mg/day) in patients with comorbidities (in particular, diabetes mellitus and hypertension).Despite numerous study limitations, this systematic review suggests three potential synergistic risk factors for cardiovascular complications after exposure to HSCD: a high sodium intake (≥ 1,500 mg/day), a long duration of exposure, and the presence of comorbidities. Further studies are required to characterize this iatrogenic risk.PROSPERO CRD42016047086

Disaster Vulnerability and Evacuation Readiness: Coastal Mobile Home Residents in Florida

This article examines disaster preparedness in a highly vulnerable population, mobile home park residents in hurricane-prone areas. The vulnerabilities of this population mandate evacuation as the only viable disaster response strategy, but this does not always happen. In order to explore evacuation decision making, interviews were conducted with 75 mobile home park residents in Ruskin, Florida. Descriptive results build on a conceptualization of physical, structural, socio-economic, and “residual” disaster vulnerability; the latter is defined as a combination of experiences, perceptions, and preparations that inhibit the willingness and abilities of respondents to protect themselves. While residents generally prepared for disasters, evacuation plans were troubling. Barriers to evacuation based on measured vulnerabilities remained unclear, and analysis of responses failed to explain respondents’ varying evacuation preparations. Future research needs to address differential evacuation behaviors among mobile home park residents. We further conclude that disaster preparation and education need to address the special risks of this and other vulnerable populations better