This critical review describes some developments on the chemistry of fluorescent and colorimetric molecular probes or chemosensors, based on polyamines and associated compounds having oxygen and/or sulfur as donor atoms. The reported systems are essentially based on some selected published work in this field in the last five years, and in the work developed by the authors from 2000 onwards. Some interesting properties beyond sensing molecules, ions or/and cations by fluorescence, colorimetry as well as by MALDI-TOF MS spectrometry can arise from these systems. A short brief on different examples activated by PET (photoinduced electron transfer), ICT (internal charge transfer) and EET (electronic energy transfer) phenomena will be provided. Finally the introduction of bio-inspired compounds derived from emissive amino acid or short peptide systems and nanoparticle devices to detect metal ions will be reviewed (202 references).

Abstract-It has been generally acknowledged that the actions of glyceryl trinitrate (GTN) are a result of its bioconversion into NO. However, recent observations have thrown this idea into doubt, with many studies demonstrating that NO is present only when there are high concentrations of GTN. We have explored this discrepancy by developing a new approach that uses confocal microscopy to directly detect NO. Intracellular levels of NO in the rat aortic vascular wall have been compared with those present after incubation with 3 different NO donors (DETA-NO, 3-morpholinosydnonimine, and S-nitroso-N-acetylpenicillamine), endothelial activation with acetylcholine, or administration of GTN. We have also evaluated the relaxant effects of these treatments on isolated rings of aorta following activation of the enzyme soluble guanylyl cyclase and their inhibitory action on mitochondrial respiration, which is an index of the interaction of NO with the enzyme of the electron transport chain cytochrome C oxidase. In the case of the various NO donors and acetylcholine, we detected a concentration-dependent relationship in the intensity of vascular relaxation and degree of NO fluorescence and an increase in the

Interaction of AuNPs, AgNPs and MNPs with human serum formed a protein corona.• Methods DDA for the qualitative analysis of the protein coronas.• SWATH-MS for the quantitative analysis of the protein coronas.• The analysis of the protein coronas allowed the identification of novel biomarkers of TNBC.• Role of different protein biomarkers in the diagnosis of TNBC.

Abstract-Nitric oxide (NO) decreases cellular oxygen (O 2 ) consumption by competitively inhibiting cytochrome c oxidase. Here, we show that endogenously released endothelial NO, either basal or stimulated, can modulate O 2 consumption both throughout the thickness of conductance vessels and in the microcirculation. Furthermore, we have shown that such modulation regulates O 2 distribution to the surrounding tissues. We have demonstrated these effects by measuring O 2 consumption in blood vessels in a hypoxic chamber and O 2 distribution in the microcirculation using the fluorescent oxygen-probe Ru(phen) 3 2ϩ . Removal of NO by physical or pharmacological means, or in eNOS Ϫ/Ϫ mice, abolishes this regulatory mechanism. Our results indicate that, in addition to its well-known effect on the regulation of vascular tone, endothelial NO plays a major role in facilitating the distribution of O 2 , an action which is crucial for the adaptation of tissues, including the vessel wall itself, to hypoxia. It is possible that changes in the distribution of O 2 throughout the vessel wall may be implicated in the origin of vascular pathologies such as atherosclerosis. [eNOS]) is constantly activated by the shear stress generated by circulating blood. The resulting NO, which activates soluble guanylate cyclase (sGC), maintains a vasodilator tone which is determinant in the regulation of blood flow and pressure. 1 NO also interacts with the terminal enzyme of the electron transport chain, cytochrome c oxidase (CcO), in a manner that is competitive with oxygen (O 2 ), leading to an increase in the K m of this enzyme for O 2 and the consequent inhibition of respiration. 2 A number of studies in vascular endothelial cells 3 and in tissues 4,5 have shown that this results in a decrease in consumption of O 2 and in its redistribution away from mitochondria and toward other oxygen-dependent targets. 6 Thus NO plays a role in the subcellular profile of O 2 distribution. In this study, we have investigated this phenomenon by monitoring the dynamics of O 2 consumption and its distribution both in a variety of strips of conductance vessels from several species and in the mesenteric circulation of rats and mice. Our results indicate that NO plays a major role in facilitating O 2 distribution in these vascular tissues through its effect as an inhibitor of the mitochondrial CcO. This action, which increases as the O 2 concentration [O 2 ] decreases, might be a major factor in the adaptation of tissues to hypoxia. Materials and Methods Tissue PreparationHuman umbilical cords were obtained from the Department of Gynaecology and Obstetrics of the Hospital Doctor Peset. Vascular rings, 5 mm in length, were extracted from the middle portion of the cords. Male Sprague-Dawley rats (200 to 250 g, Harlan Laboratories, Barcelona, Spain) or wild-type (WT) and eNOS knockout (eNOS Ϫ/Ϫ ) mice (WT, C57BL/6Jx129, 20 to 25 g, UCL, London, UK) were decapitated and their thoracic aortas and pulmonary and mesenteric arteries were removed, cleaned of adhering t...

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Abstract-Nitroglycerin (GTN) tolerance was induced in vivo (rats) and in vitro (rat and human vessels). Electrochemical detection revealed that the incubation dose of GTN (5ϫ10 Ϫ6 mol/L) did not release NO or modify O 2 consumption when administered acutely. However, development of tolerance produced a decrease in both mitochondrial O 2 consumption and the K m for O 2 in animal and human vessels and endothelial cells in a noncompetitive action. GTN tolerance has been associated with impairment of GTN biotransformation through inhibition of aldehyde dehydrogenase (ALDH)-2, and with uncoupling of mitochondrial respiration. Feeding rats with mitochondrial-targeted antioxidants (mitoquinone [MQ]) and in vitro coincubation with MQ (10 Ϫ6 mol/L) or glutathione (GSH) ester (10 Ϫ4 mol/L) prevented tolerance and the effects of GTN on mitochondrial respiration and ALDH-2 activity. Biotransformation of GTN requires functionally active mitochondria and induces reactive oxygen species production and oxidative stress within this organelle, as it is inhibited by mitochondrial-targeted antioxidants and is absent in HUVEC 0 cells. Experiments analyzing complex I-dependent respiration demonstrate that its inhibition by GTN is prevented by mitochondrial-targeted antioxidants. Furthermore, in presence of succinate (10ϫ10 Ϫ3 mol/L), a complex II electron donor added to bypass complex I-dependent respiration, GTN-treated cells exhibited O 2 consumption rates similar to those of controls, thus suggesting that complex I was affected by GTN. We propose that, following prolonged treatment with GTN in addition to ALDH-2, complex I is a target for mitochondrially generated reactive oxygen species. Our data also suggest a role for mitochondrial-targeted antioxidants as therapeutic tools in the control of the tolerance that accompanies chronic nitrate use. ) have generally been attributed to its bioconversion into the relaxant agent nitric oxide (NO), which acts on the enzyme soluble guanylate cyclase (sGC). [1][2][3] However, most studies that support the existence of such a pathway have demonstrated increases of NO only when GTN concentrations considerably exceeded the plasma levels reached during clinical dosing. 4 Moreover, the involvement of other NO-related species in the actions of GTN when used at clinically relevant concentrations is also under debate. 5,6 Different enzymes have been implicated in the bioconversion of GTN, in particular, glutathione S-transferases, 7 the cytochrome p450 system, 8 and xanthine oxidoreductase, 9 although the most recent evidence suggests a central role for mitochondrial aldehyde dehydrogenase (ALDH)-2. 10 -13 The medical use of GTN is limited by the development of tolerance, which occurs following prolonged administration or the application of high doses. This phenomenon has been related to various mechanisms, in particular, desensitization of sGC, 14 and, mainly, impairment of GTN biotransformation by inhibition of ALDH-2. 10 -12 These actions, like others associated with GTN, have been linked to a...

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