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Emulsion-based gels with thermally switchable transparency

Kenji Aramaki, Kazuki Masuda, Ryosuke Horie and Carlos Rodríguez-Abreub

Colloids and Surfaces A: Physicochemical and Engineering Aspects, 533,302-307, 2017

Optical transparency (high light transmittance) of materials is relevant for various applications, and it is of particular interest if it can be switched by stimuli such as temperature. Oil-in-liquid crystal (O/LC) emulsions are a kind of soft materials with excellent workability because of their gel-like and self-standing characteristics. Transparent O/LC emulsions can be obtained by matching the refractive indices of dispersed (oil) and continuous (liquid crystalline) phases. If the refractive indices of the dispersed and continuous phases have different temperature sensitivity, i.e., different thermo-optic coefficients, thermally switchable optical transparency can be realized. In this paper, we report the effect of temperature on the light transmittance of oil-in-cubic phase (O/I1) emulsions in water/poly(oxyethylene) dodecyl ether (C12EO25)/oil systems, with isopropyl hexanoate (IPH) and isopropyl myristate (IPM) as oil components. Transparent emulsions were obtained at 25 °C at surfactant mass fractions in water (WS) of 0.5 for IPH and 0.7 for IPM. The temperature range at which the samples remained transparent was 20–50 °C for the IPH system and 10–70 °C for the IPM system, away from which, the samples were turbid, confirming that the transparency is thermally switchable. We also confirmed the reversibility of switching transparency in the IPH system. Refractive indices of pure oils and the I1 phase were measured at different temperatures. The refractive indices changed linearly with temperature, but the slope (i.e., the thermo-optic coefficient) was different depending on the type of oil, surfactant concentration, and oil solubilization in the I1 phase, which explains the different effect of temperature on the optical transparency of the IPH and IPM systems.

Biobarcode assay for the oral anticoagulant acenocoumarol

Broto, M., Salvador, J.P., Galve, R., Marco, M.P.

Talanta, 178, pp. 308-314, 2018

A novel approach for therapeutic drug monitoring of oral anticoagulants (OA) in clinical samples is reported, based on a NP-based biobarcode assay. The proposed strategy uses specific antibodies for acenocumarol (ACL) covalently bound to magnetic particles (pAb236-MP) and a bioconjugate competitor (hACL-BSA) linked to encoded polystyrene probes (hACL-BSA-ePSP) on a classical competitive immunochemical format. By using this scheme ACL can be detected in low nM range (LOD, 0.96 ± 0.26, N = 3, in buffer) even in complex samples such as serum or plasma (LOD 4 ± 1). The assay shows a high reproducibility (%CV 1.1 day-to-day) and is robust, as it is demonstrated by the fact that ACL can be quantified in complex biological samples with a very good accuracy (slope = 0.97 and R2 = 0.91, of the linear regression obtained when analyzing spiked vs measured values). Moreover, we have demonstrated that the biobarcode approach has the potential to overcome one of the main challenges of the multiplexed diagnostic, which is the possibility to measure in a single run biomarker targets present at different concentration ranges. Thus, it has been proven that the signal and the detectability can be modulated by just modifying the oligonucleotide load of the encoded probes. This fact opens the door for combining in the same assay encoded probes with the necessary oligonucleotide load to achieve the detectability required for each biomarker target.

MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells

Lourdes Sánchez-Cid, Mònica Pons, Juan José Lozano, Nuria Rubio, Marta Guerra-Rebollo, Aroa Soriano, Laia Paris-Coderch, Miquel F. Segura, Raquel Fueyo, Judit Arguimbau, Erika Zodda, Raquel Bermudo, Immaculada Alonso, Xavier Caparrós, Marta Cascante, Arash Rafii, Yibin Kang, Marian Martínez-Balbás, Stephen J. Weiss, Jerónimo Blanco, Montserrat Muñoz, Pedro L. Fernández and Timothy M. Thomson

Oncotarget. 2017

MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo. MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells.

Cationic nioplexes-in-polysaccharide-based hydrogels as versatile biodegradable hybrid materials to deliver nucleic acids

Grijalvo, S.; Alagia, A.; Puras, G.; Zárate, J.; Mayr, J.; Pedraz, J. L.; Eritja, R.; Díaz, D. D.

J. Mater. Chem. B 2017

Two polysaccharide-based hydrogels made of only ?-carrageenan (4%; w/v) or of a mixture of methylcellulose:?-carrageenan (2%; w/v) were used to encapsulate cationic nioplexes. These vesicular particles were made of a synthetic aminolipid and polysorbate-80 (Tween-80), as a non-ionic surfactant agent. According to oscillatory rheological measurements, the presence of nioplexes did not compromise the mechanical integrity of the gels. In vitro niosomal release experiments demonstrated the liberation of nioplexes up to 24 h, and the curves were fitted according to Higuchi, Korsmeyer-Peppas and Weibull equation models, which indicated Fickian-diffusion controlled mechanisms. Besides nioplexes, cervical cancer cells were also entrapped within the biohydrogels. Cell release confirmed that these materials did not affect the cell viability, allowing cells to spread and proliferate after 24 h. The applicability of these biocompatible hydrogels was also extended to gene delivery. In this regard, the best silencing activities were found when cationic niosomes were complexed with antisense oligonucleotides in KC hydrogels. Nioplexes were able to release through the hydrogel and promoted silencing of luciferase expression in the presence of serum without using commercially available cationic lipids. Overall, the formation of such hybrid materials by integrating cationic nioplexes within biodegradable hydrogels provides a new perspective for the delivery of macromolecular therapeutics.

The role of sorption processes in the removal of pharmaceuticals by fungal treatment of wastewater

D. Lucas, F. Castellet-Rovira, M. Villagrasa, M. Badia-Fabregat, D. Barceló, c, T. Vicent, G. Caminal, M. Sarrà, S. Rodríguez-Mozaz

Science of The Total Environment 610–611, 1147–1153, 2018

The contribution of the sorption processes in the elimination of pharmaceuticals (PhACs) during the fungal treatment of wastewater has been evaluated in this work. The sorption of four PhACs (carbamazepine, diclofenac, iopromide and venlafaxine) by 6 different fungi was first evaluated in batch experiments. Concentrations of PhACs in both liquid and solid (biomass) matrices from the fungal treatment were measured. Contribution of the sorption to the total removal of pollutants ranged between 3% and 13% in relation to the initial amount. The sorption of 47 PhACs in fungi was also evaluated in a fungal treatment performed in 26 days in a continuous bioreactor treating wastewater from a veterinary hospital. PhACs levels measured in the fungal biomass were similar to those detected in conventional wastewater treatment (WWTP) sludge. This may suggest the necessity of manage fungal biomass as waste in the same manner that the WWTP sludge is managed.

Pharmacokinetics of Mephedrone and Its Metabolites in Human by LC-MS/MS

Eulàlia Olesti, Magí Farré, Esther Papaseit, Aristotelis Krotonoulas, Mitona Pujadas, Rafael de la Torre and Óscar J. Pozo

The AAPS Journal, pp 1–12 2017

Mephedrone is a synthetic cathinone consumed as a recreational drug. Recently, it was identified several of its metabolites in vivo in humans but there is little information about its pharmacokinetics in plasma and urine. Although several analytical methods have been proposed for mephedrone quantification in different matrices, none are available for its metabolites. Therefore, the aim of the study was to develop and validate an analytical method using liquid chromatography-tandem mass spectrometry for the quantification of mephedrone, nor-mephedrone, N-succinyl-nor-mephedrone, 1'-dihydro-mephedrone, and 4'-carboxy-mephedrone. The method was validated in human plasma and urine and in rat brain homogenates. Six healthy male subjects, recreational users of new psychoactive substances, ingested 150 mg of mephedrone within the context of a clinical trial. 4'-Carboxy-mephedrone, followed by nor-mephedrone, was the most abundant metabolites found in plasma. Dihydro-mephedrone represented 10% of the amount of mephedrone in plasma and N-succinyl-nor-mephedrone

CRISPR/Cas9-Mediated Knockin Application in Cell Therapy: A Non-viral Procedure for Bystander Treatment of Glioma in Mice

Oscar Meca-Cortés, Marta Guerra-Rebollo, Cristina Garrido, Salvador Borrós, Nuria Rubio and Jeronimo Blanco

Molecular Therapy - Nucleic Acids, 8, 395-403, 2017

The use of non-viral procedures, together with CRISPR/Cas9 genome-editing technology, allows the insertion of single-copy therapeutic genes at pre-determined genomic sites, overcoming safety limitations resulting from random gene insertions of viral vectors with potential for genome damage. In this study, we demonstrate that combination of non-viral gene delivery and CRISPR/Cas9-mediated knockin via homology-directed repair can replace the use of viral vectors for the generation of genetically modified therapeutic cells. We custom-modified human adipose mesenchymal stem cells (hAMSCs), using electroporation as a transfection method and CRISPR/Cas9-mediated knockin for the introduction and stable expression of a 3 kb DNA fragment including the eGFP (selectable marker) and a variant of the herpes simplex virus 1 thymidine kinase genes (therapeutic gene), under the control of the human elongation factor 1 alpha promoter in exon 5 of the endogenous thymidine kinase 2 gene. Using a U87 glioma model in SCID mice, we show that the therapeutic capacity of the new CRISPR/Cas9-engineered hAMSCs is equivalent to that of therapeutic hAMSCs generated by introduction of the same therapeutic gene by transduction with a lentiviral vector previously published by our group. This strategy should be of general use to other applications requiring genetic modification of therapeutic cells.


Design of Hückel–Möbius Topological Switches with High Nonlinear Optical Properties

Miquel Torrent-Sucarrat, Sara Navarro, Enrique Marcos, Josep M. Anglada and Josep M. Luis

J. Phys. Chem. C, 121 (35), 19348–19357, 2017

The macrocyclic ring of expanded porphyrins presents a conformational versatility that leads to original structural motifs and generates unique Hückel-to-Möbius topological switches. These systems can act as optoelectronic materials, and their range of applicability depends on the high values of the nonlinear optical properties (NLOPs) and the large differences between the Hückel and Möbius structures. With the aim to design new topological switches with the optimum NLOPs, we have performed a DFT computational study on the effect of three different geometric and electronic factors of the meso-substituents: (i) their electron-withdrawing and -releasing character; (ii) their distribution along the porphyrin ring; and (iii) the length of the conjugation path. In this work, we report the electronic and vibrational contributions to static and dynamic NLOPs of the Hückel and Möbius conformations of 18 meso-substituted [28]-hexaphyrins. These systems can achieve first and second hyperpolarizability values around 1 × 105 and 2 × 107 au, respectively, and differences between the Möbius and Hückel conformations around 4 × 104 and 5 × 106 au, respectively. From our results, we conclude that efficient NLOP topological switches can be obtained from push–pull porphyrins with a π-conjugated spacer and strong electron-withdrawing and -releasing groups located on opposite sides of the skeleton ring.

Allosteric control of an asymmetric transduction in a G protein-coupled receptor heterodimer

Junke Liu, Zongyong Zhang, David Moreno-Delgado, James AR Dalton, Xavier Rovira, Ana Trapero, Cyril Goudet, Amadeu Llebaria, Jesús Giraldo, Qilin Yuan, Philippe Rondard, Siluo Huang, Jianfeng Liu and Jean-Philippe Pin

eLife 2017

GPCRs play critical roles in cell communication. Although GPCRs can form heteromers, their role in signaling remains elusive. Here we used rat metabotropic glutamate (mGlu) receptors as prototypical dimers to study the functional interaction between each subunit. mGluRs can form both constitutive homo- and heterodimers. Whereas both mGlu2 and mGlu4 couple to G proteins, G protein activation is mediated by mGlu4 heptahelical domain (HD) exclusively in mGlu2-4 heterodimers. Such asymmetric transduction results from the action of both the dimeric extracellular domain, and an allosteric activation by the partially-activated non-functional mGlu2 HD. G proteins activation by mGlu2 HD occurs if either the mGlu2 HD is occupied by a positive allosteric modulator or if mGlu4 HD is inhibited by a negative modulator. These data revealed an oriented asymmetry in mGlu heterodimers that can be controlled with allosteric modulators. They provide new insight on the allosteric interaction between subunits in a GPCR dimer.

Short-term peripheral sensitization by brief exposure to pheromone components in Spodoptera littoralis

S. López, A. Guerrero, M. J. Bleda and C. Quero

Journal of Comparative Physiology A, 2017

In insects, the olfactory system displays a high degree of plasticity. In Spodoptera littoralis, pre-exposure of males to the sex pheromone has been shown to increase the sensitivity of the olfactory sensory neurons at peripheral level. In this study, we have investigated this sensitization effect by recording the electroantennographic responses of male antennae to the major sex pheromone component (Z,E)-9,11-tetradecadienyl acetate and to the minor components (Z,E)-9,12-tetradecadienyl acetate and (Z)-9-tetradecenyl acetate. Responses to the conjugated diene acetate at 1 and 10 µg and to the unconjugated ester at 10 µg at three different times (11, 22 and 33 min) after pre-exposure (T = 0 min) were significantly higher than those at T = 0, whereas no increase of sensitivity to the pheromone was elicited by any dose of the minor monoene acetate. In addition, pre-exposed antennae to sub-threshold amounts (0.1, 1 and 10 ng) of the major pheromone component also induced an increased response to the chemical at different times (5 and 15 min) after exposure. Our results revealed that pre-exposed isolated antennae display a short-term higher sensitivity at the peripheral level when compared to naive antennae. In addition, we provide evidence of a peripheral sensitization mediated not only by the major pheromone component, but also by the minor unconjugated diene acetate, and the induction of this sensitivity appears to be dependent on the pre-exposure dose and the time span between pre-exposure and subsequent recordings. Possible implications of the sensitization effect displayed by the minor component for a more effective discrimination of the pheromone bouquets of other closely related species are highlighted.

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