Estudio de la interacción de SALL1, causante del Síndrome de Townes-Brocks, con la E3 SUMO ligasa CBX4.

[ES] SALL1 es un represor transcripcional del tipo dedos de zinc que regula la organogénesis y el desarrollo animal. Las proteínas de la familia SALL sufren modificaciones postraduccionales por miembros de la familia de ubiquitina, como por ejemplo SUMO (Small Ubiquitin-related MOdifier). Para entender la importancia de esta modificación postraduccional en la interacción de SALL1 con otras proteínas, se analizó la relación de SALL1 con CBX4, siendo ésta una E3 SUMO-ligasa y una subunidad del complejo de represión Polycomb 1 (PRC1). Tanto SALL1 silvestre (WT) como un mutante de SALL1 que no puede ser modificado por SUMO, SALL1∆SUMO, interaccionan con CBX4. Observaciones previas del laboratorio sugirieron que la presencia de SALL1 influye en los niveles de CBX4. En este trabajo se ha demostrado que SALL1 no influye en los niveles de CBX4 de manera transcripcional, sino de manera postranscripcional. También se ha demostrado la capacidad de SALL1 para estabilizar a CBX4, haciendo que su ubiquitinación y su degradación se reduzcan. Asimismo, SALL1 contribuye a la represión de los genes diana de CBX4, mientras que SALL1∆SUMO no produce el mismo efecto. Estos resultados indican que la SUMOilación de SALL1 es necesaria para aumentar la actividad represora de CBX4, aunque no para su estabilización

CO-Releasing Binuclear Rhodium Complexes as Inhibitors of Nitric Oxide Generation in Stimulated Macrophages

Nontoxic CO-releasing dirhodium complexes act as inhibitors of NO in stimulated macrophage cells, suggesting that novel antiinflammatory treatments could involve the use of these types of binuclear complexes

Delivery Modulation in Silica Mesoporous Supports via Alkyl Chain Pore Outlet Decoration

This article focuses on the study of the release rate in a family of modified silica mesoporous supports. A collection of solids containing ethyl, butyl, hexyl, octyl, decyl, octadecyl, docosyl, and triacontyl groups anchored on the pore outlets of mesoporous MCM-41 has been prepared and characterized. Controlled release from pore voids has been studied through the delivery of the dye complex tris­(2,2′-bipyridyl)­ruthenium­(II). Delivery rates were found to be dependent on the alkyl chain length anchored on the pore outlets of the mesoporous scaffolding. Moreover, release rates follow a Higuchi diffusion model, and Higuchi constants for the different hybrid solids have been calculated. A decrease of the Higuchi constants was observed as the alkyl chain used to tune the release profile is longer, confirming the effect that the different alkyl chains anchored into the pore mouths exerted on the delivery of the cargo. Furthermore, to better understand the relation between pore outlets decoration and release rate, studies using molecular dynamics simulations employing force-field methods have been carried out. A good agreement between the calculations and the experimental observations was observed

A Chromo-Fluorogenic Synthetic “Canary” for CO Detection Based on a Pyrenylvinyl Ruthenium(II) Complex

The chromo-fluorogenic detection of carbon monoxide in air has been achieved using a simple, inexpensive system based on ruthenium­(II). This probe shows exceptional sensitivity and selectivity in its sensing behavior in the solid state. A color response visible to the naked eye is observed at 5 ppb of CO, and a remarkably clear color change occurs from orange to yellow at the onset of toxic CO concentrations (100 ppm) in air. Even greater sensitivity (1 ppb) can be achieved through a substantial increase in turn-on emission fluorescence in the presence of carbon monoxide, both in air and in solution. No response is observed with other gases including water vapor. Immobilization of the probe on a cellulose strip allows the system to be applied in its current form in a simple optoelectronic device to give a numerical reading and/or alarm

Tetrathiafulvalene-Capped Hybrid Materials for the Optical Detection of Explosives

Mesoporous silica microparticles capped with TTF moieties and containing a ruthenium dye in the pores were used for the turn-on optical detection of the nitroaromatic explosives Tetryl and TNT via a selective pore uncapping and release of the entrapped dye

Gated Mesoporous Silica Nanocarriers for a “Two-Step” Targeted System to Colonic Tissue

Colon targeted drug delivery is highly relevant not only to treat colonic local diseases but also for systemic therapies. Mesoporous silica nanoparticles (MSNs) have been demonstrated as useful systems for controlled drug release given their biocompatibility and the possibility of designing gated systems able to release cargo only upon the presence of certain stimuli. We report herein the preparation of three gated MSNs able to deliver their cargo triggered by different stimuli (redox ambient (<b>S1</b>), enzymatic hydrolysis (<b>S2</b>), and a surfactant or being in contact with cell membrane (<b>S3</b>)) and their performance in solution and <i>in vitro</i> with Caco-2 cells. Safranin O dye was used as a model drug to track cargo fate. Studies of cargo permeability in Caco-2 monolayers demonstrated that intracellular safranin O levels were significantly higher in Caco-2 monolayers when using MSNs compared to those of free dye. Internalization assays indicated that <b>S2</b> nanoparticles were taken up by cells via endocytosis. <b>S2</b> nanoparticles were selected for <i>in vivo</i> tests in rats. For <i>in vivo</i> assays, capsules were filled with <b>S2</b> nanoparticles and coated with Eudragit FS 30 D to target colon. The enteric coated capsule containing the MSNs was able to deliver <b>S2</b> nanoparticles in colon tissue (first step), and then nanoparticles were able to deliver safranin O inside the colonic cells after the enzymatic stimuli (second step). This resulted in high levels of safranin O in colonic tissue combined with low dye levels in plasma and body tissues. The results suggested that this combination of enzyme-responsive gated MSNs and enteric coated capsules may improve the absorption of drugs in colon to treat local diseases with a reduction of systemic effects

Polymer Composites Containing Gated Mesoporous Materials for On-Command Controlled Release

Polyamidic nanofibrous membranes containing gated silica mesoporous particles, acting as carriers, are described as novel hybrid composite materials for encapsulation and on-command delivery of garlic extracts. The carrier system consists of MCM-41 solids functionalized in the outer surface, with linear polyamines (solid <b>P1</b>) and with hydrolyzed starch (solid <b>P2</b>), both acting as molecular gates. Those particles were adsorbed on electospun nylon-6 nanofibrous membranes yielding to composite materials <b>M1</b> and <b>M2</b>. FE-SEM analysis confirmed the presence of particles incorporated on the nylon nanofibers. The release of the entrapped molecules (garlic extract) from the <b>P1</b>, <b>P2</b>, <b>M1</b>, and <b>M2</b> materials was evaluated using cyclic voltammetry measurements. Electrochemical studies showed that at acidic pH <b>P1</b> and <b>M1</b> were unable to release their entrapped cargo (closed gate), whereas at neutral pH both materials release their loading (open gate). Dealing with <b>P2</b> and <b>M2</b> materials, in the absence of pancreatin a negligible release is observed (closed gate), whereas in the presence of enzyme the load is freely to diffuse to the solution. These newly developed composite nanomaterials, provide a homogeneous easy-to-handle system with controlled delivery and bioactive-protective features, having potential applications on pharmacology, medical and engineering field

Imidazoanthraquinone Derivatives for the Chromofluorogenic Sensing of Basic Anions and Trivalent Metal Cations

Four imidazoanthraquinone derivatives (<b>2a</b>–<b>d</b>) were synthesized and characterized and their coordination behavior against selected anions and cations tested. Acetonitrile solutions of probes showed charge-transfer absorptions in the 407–465 nm range. The four probes emitted in the 533–571 nm interval. The recognition ability of <b>2a</b>–<b>d</b> was evaluated in the presence of F^–, Cl^–, Br^–, I^–, OCN^–, BzO^–, ClO₄^–, AcO^–, HSO₄^–, H₂PO₄^–, and CN^–. Only F^–, AcO^–, and H₂PO₄^– induced a new red-shifted absorption band that was attributed to a deprotonation process involving the amine moiety of the imidazole ring. Moreover, upon increasing quantities of F^–, AcO^–, and H₂PO₄^–, moderate quenching was induced in the emission of <b>2a</b>–<b>d</b> together with the appearance of a new red-shifted band. The UV–visible and emission behavior of the four probes in the presence of Cu²⁺, Co²⁺, Mg²⁺, Fe³⁺, Ba²⁺, Fe²⁺, Ni²⁺, Ca²⁺, Zn²⁺, Pb²⁺, Cd²⁺, Cr³⁺, Al³⁺, K⁺, and Li⁺ was also assessed. Only addition of Fe³⁺, Cr³⁺, and Al³⁺ caused a new blue-shifted band in <b>2a</b>–<b>d</b> that was ascribed to a preferential coordination with the acceptor part of the probes. Moreover, an important quenching of the emission was observed which was ascribed to the interaction between these trivalent cations and <b>2a</b>–<b>d</b>