The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one-third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling-centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes.
Experimental data for the density, viscosity, refractive index and surface tension of four sulfonium-and ammonium-based Ionic Liquids (ILs) with the common bis (trifluoromethylsulfonyl) . Based on the gathered results and on data taken from literature, the impact of the cation isomerism and of the size of the aliphatic tails, as well as the effect resulting from the substitution of a nitrogen by a sulfur atom as the cation central atom, on the thermophysical properties of sulfonium-and ammonium-based ILs is here discussed. Remarkably, more symmetric cations present a lower viscosity for the same, and sometimes even for higher, alkyl chain lengths at the cation. Additional derivative properties, such as the isobaric thermal expansion coefficient, the surface thermodynamic properties and the critical temperature for the investigated ILs were also estimated and are presented and discussed.
Due to the close relation between oxidative stress and a plethora of inflammatory diseases, antioxidants have received an increased attention for incorporation into dermatological products. Their use and absorption is however limited by their low solubility in water-rich formulations. Herein, a set of novel cholinium-based salts, namely dicholinium ellagate and cholinium caffeate, syringate, vanillate, gallate and salicylate were synthetized and characterized. Their melting and decomposition temperatures, water solubility, and toxicological, antioxidant, cytotoxicity and pro-/ anti-inflammatory activities were addressed. These new salts, exclusively composed of ions derived from natural sources, display a high thermal stability -up to 150 ºC. The synthesized compounds are significantly more soluble in water (in average, 3 orders of magnitude higher) than the corresponding phenolic acids. Furthermore, they present not only similar but even higher antioxidant and anti-inflammatory activities, as well as comparable cytotoxicity and lower ecotoxicity profiles than their acidic precursors. Amongst all the investigated salts, dicholinium ellagate is the most promising synthesized salt when considering the respective antioxidant and anti-inflammatory activities. Since all the synthesized salts are based on the cholinium cation, they can further be envisaged as essential nutrients to be used in oral drugs.
Aljustrel mining area is located in the Iberian Pyrite Belt, one of the greatest concentrations of massive sulphide deposits that extends from Lousal (Portugal) to Aznalcóllar (Spain). The surrounding streams, Roxo, Água Azeda and Água Forte, are influenced by the erosion of the tailing deposits and the input of acid mine drainage (AMD) from the abandoned Aljustrel pyrite mines, recently reopened in 2007. The purpose of this study was to understand how these adverse conditions influenced the stream sediments, water quality and periphytic diatom communities and establish the pre-restoration local conditions to judge the success of rehabilitation program now under way. For stream sediments, the highest metal concentration samples were found at sites F, G and H. Arsenic, Cu, Fe, Pb and Sb detected concentrations, generally exceeded the probable effect concentration values reaching level 4: the highest toxicity level. In surficial water samples of AMD affected sites (F, G and H), low pH values (1.5 to 3.5) and high metal concentrations of As (6,837 μg L
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