Curcumin Analogue C1 Promotes Hex and Gal Recruitment to the Plasma Membrane via mTORC1-Independent TFEB Activation.

The monocarbonyl analogue of curcumin (1E,4E)-1,5-Bis(2-methoxyphenyl)penta-1,4-dien-3-one (C1) has been used as a specific activator of the master gene transcription factor EB (TFEB) to correlate the activation of this nuclear factor with the increased activity of lysosomal glycohydrolases and their recruitment to the cell surface. The presence of active lysosomal glycohydrolases associated with the lipid microdomains has been extensively demonstrated, and their role in glycosphingolipid (GSL) remodeling in both physiological and pathological conditions, such as neurodegenerative disorders, has been suggested. Here, we demonstrate that Jurkat cell stimulation elicits TFEB nuclear translocation and an increase of both the expression of hexosaminidase subunit beta (HEXB), hexosaminidase subunit alpha (HEXA), and galactosidase beta 1 (GLB1) genes, and the recruitment of ß-hexosaminidase (Hex, EC 3.2.1.52) and ß-galactosidase (Gal, EC 3.2.1.23) on lipid microdomains. Treatment of Jurkat cells with the curcumin analogue C1 also resulted in an increase of both lysosomal glycohydrolase activity and their targeting to the cell surface. Similar effects of C1 on lysosomal glycohydrolase expression and their recruitment to lipid microdomains was observed by treating the SH-SY5Y neuroblastoma cell line; the effects of C1 treatment were abolished by TFEB silencing. Together, these results clearly demonstrate the existence of a direct link between TFEB nuclear translocation and the transport of Hex and Gal from lysosomes to the plasma membrane.

A green deep eutectic solvent dispersive liquid-liquid micro-extraction (DES-DLLME) for the UHPLC-PDA determination of oxyprenylated phenylpropanoids in olive, soy, peanuts, corn, and sunflower oil.

A green dispersive liquid-liquid microextraction (DLLME) using deep eutectic solvent (DES) as the extracting solvent has been developed and applied for the simultaneous quantification of ferulic acid, umbelliferone, boropinic acid, 7-isopentenyloxycoumarin, 4'-geranyloxyferulic acid (GOFA), and auraptene in some vegetable oils using ultra high performance liquid chromatography (UHPLC) with photodiode array detection (PDA). All parameters in the extraction step, including selection and loading of both extracting and dispersing solvents, amount of both extractant and disperser solvent were investigated and optimized. PhAA/TMG DES achieved higher recovery and enrichment factor compared to other DESs. The validated method showed good linearity with correlation coefficients, r2>0.9990 for all the analytes. Furthermore, this is the first time that eco-friendly solvents are used for the extraction of oxyprenylated phenylpropanoids and the corresponding extract analyzed with ultra high performance liquid chromatography with photodiode array detection.

Optical Communication among Oscillatory Reactions and Photo-Excitable Systems: UV and Visible Radiation Can Synchronize Artificial Neuron Models.

Neuromorphic engineering promises to have a revolutionary impact in our societies. A strategy to develop artificial neurons (ANs) is to use oscillatory and excitable chemical systems. Herein, we use UV and visible radiation as both excitatory and inhibitory signals for the communication among oscillatory reactions, such as the Belousov-Zhabotinsky and the chemiluminescent Orban transformations, and photo-excitable photochromic and fluorescent species. We present the experimental results and the simulations regarding pairs of ANs communicating by either one or two optical signals, and triads of ANs arranged in both feed-forward and recurrent networks. We find that the ANs, powered chemically and/or by the energy of electromagnetic radiation, can give rise to the emergent properties of in-phase, out-of-phase, anti-phase synchronizations and phase-locking, dynamically mimicking the communication among real neurons.

Ionic Conductivity as a Tool To Study Biocidal Activity of Sulfobetaine Micelles against Saccharomyces cerevisiae Model Cells.

Zwitterionic sulfobetaine surfactants are used in pharmaceutical or biomedical applications for the solubilization and delivery of hydrophobic molecules in aqueous medium or in biological environments. In a screening on the biocidal activity of synthetic surfactants on microbial cells, remarkable results have emerged with sulfobetaine amphiphiles. The interaction between eight zwitterionic sulfobetaine amphiphiles and Saccharomyces cerevisiae model cells was therefore analyzed. S. cerevisiae yeast cells were chosen, as they are a widely used unicellular eukaryotic model organism in cell biology. Conductivity measurements were used to investigate the interaction between surfactant solution and cells. Viable counts measurements were performed, and the mortality data correlated with the conductivity profiles very well, in terms of the inflection points (IPs) observed in the curves and in terms of supramolecular properties of the aggregates. A Fourier transform infrared (FTIR)-based bioassay was then performed to determine the metabolomic stress-response of the cells subjected to the action of zwitterionic surfactants. The surfactants showed nodal concentration (IPs) with all the techniques in their activities, corresponding to the critical micellar concentrations of the amphiphiles. This is due to the pseudocationic behavior of sulfobetaine micelles, because of their charge distribution and charge densities. This behavior permits the interaction of the micellar aggregates with the cells, and the structure of the surfactant monomers has impact on the mortality and the metabolomic response data observed. On the other hand, the concentrations that are necessary to provoke a biocidal activity do not promote these amphiphiles as potential antimicrobial agents. In fact, they are much higher than the ones of cationic surfactants.

Spectroscopic investigation of interactions of new potential anticancer drugs with DNA and non-ionic micelles.

Photophysical properties of some azinium iodides in aqueous solution of nanostructured systems as DNA and nonionic micelles were investigated using steady-state and ultrafast time-resolved spectroscopy. Spectrophotometric and fluorimetric titrations of the investigated compounds with salmon testes DNA supplied evidence of a good interaction between the salts and DNA with binding constants of 10(4)-10(6) M(-1), making them interesting for pharmaceutical applications. The interaction with DNA also changes the photobehavior of the compounds, increasing the radiative deactivation pathway to the detriment of internal conversion and slowing down the excited state dynamics. The interaction of the azinium salts with the nonionic surfactant Triton X-100 from premicellar to postmicellar concentration was studied by spectrophotometric and fluorimetric titrations evidencing the ability of the micelles to associate the studied salts in their hydrophobic portion and to release them in the presence of DNA, acting as promising drug carriers. Also transient absorption spectroscopy with femtosecond resolution demonstrated the insertion of the investigated compounds into micellar aggregates. Preliminary measurements by confocal fluorescence microscopy on MCF-7 cells in the presence of the studied azinium salts showed that they are able to cross the cellular membrane and that their cytotoxicity can be expressed through interaction with DNA (RNA). In fact, they showed a significant fluorescence signal in all cell compartments, particularly (for 2 and 3) into punctuate structures within the nuclei compatible with a localization into the nucleoli.