STAT3, a hub protein of cellular signaling pathways, is triggered by β-hexaclorocyclohexane

Background: Organochlorine pesticides (OCPs) are widely distributed in the environment and their toxicity is mostly associated with the molecular mechanisms of endocrine disruption. Among OCPs, particular attention was focused on the effects of β-hexaclorocyclohexane (β-HCH), a widely common pollutant. A detailed epidemiological study carried out on exposed population in the “Valle del Sacco” found correlations between the incidence of a wide range of diseases and the occurrence of β-HCH contamination. Taking into account the pleiotropic role of the protein signal transducer and activator of transcription 3 (STAT3), its function as a hub protein in cellular signaling pathways triggered by β-HCH was investigated in different cell lines corresponding to tissues that are especially vulnerable to damage by environmental pollutants. Materials and Methods: Human prostate cancer (LNCaP), human breast cancer (MCF-7 and MDA-MB 468), and human hepatoma (HepG2) cell lines were treated with 10 µM β-HCH in the presence or absence of specific inhibitors for different receptors. All samples were subjected to analysis by immunoblotting and RT-qPCR. Results and Conclusions: The preliminary results allow us to hypothesize the involvement of STAT3, through both its canonical and non-canonical pathways, in response to β-HCH. Moreover, we ascertained the role of STAT3 as a master regulator of energy metabolism via the altered expression and localization of HIF-1α and PKM2, respectively, resulting in a Warburg-like effect

Effect of testosterone metabolites on ABC half-transporter relative gene expression in X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disorder associated with reduced very long-chain fatty acid beta-oxidation, mainly affecting the nervous system, the adrenal cortex and the testes. The clinical manifestations of hypogonadism, alopecia and the impairment of the enzyme 5alpha-reductase, which converts testosterone into dihydrotestosterone, clearly point to an involvement of androgens in this pathology. The disease is characterized by mutations in the ABCD1 gene, which codes for the peroxisomal ABC half-transporter ALDP, and by a broad range of clinical manifestations. The altered function of ALDP can be compensated by the overexpression of proteins belonging to the same family of ABC half-transporters. A promising therapeutic approach is represented by the activation of these proteins by specific agonists. In this study we evaluated the effect of the testosterone metabolite dihydrotestosterone (DHT) and 5alpha-androstan-3alpha,17beta-diol (3alpha-diol) on the expression of the ABC half-transporters encoded by the ABCD2 and ABCD3 genes, in fibroblasts drawn from controls and from two affected brothers. The two patients presented the same mutation in exon 9 but had different clinical manifestations, one patient being asymptomatic and the second one severely affected. When the cells were stimulated with testosterone metabolites, only the severely affected patient showed a significant increase in ABCD2 mRNA levels, while the ABCD3 expression remained unchanged in both patients

In vitro cytotoxicity assessment of monocationic and dicationic pyridinium-based ionic liquids on HeLa, MCF-7, BGM and EA.hy926 cell lines

Dicationic ionic liquids (ILs) generally possess higher thermal and electrochemical stability than the analogous monocationic ILs, which makes them more suitable for high-temperature applications as solvents for organic reactions, lubricants or stationary phase in gas chromatography. However, knowledge on dicationic IL cytotoxicity is still scarce. Here we explore the cytotoxicity of twelve mono- and dicationic pyridinium-based ILs on HeLa, MCF-7, BGM and EA.hy926 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle arrest assays, apoptosis experiments and orange staining were carried out. The results showed that dicationic ILs are generally less cytotoxic than their monocationic counterparts. In monocationic ILs, cytotoxicity was stronger when they contain long alkyl chains, because of their higher lipophilicity. However, the full effect of the length of the linkage alkyl chain of dicationic ILs on cytotoxicity is not clear probably because the chain is “trapped” between both cationic moieties. IL cytotoxicity is highly dependent on the cell type, and HeLa cells exposed to [C12Pyr]Br die via apoptosis. The present study increases our knowledge of IL cytotoxicity on human and monkey cells and clarifies the cell death mechanism. The results suggest that dicationic ILs offer the potential to replace some monocationic ILs because of their lower cytotoxicity.This work was partially supported by the European Commission (FEDER/ERDF) and the Spanish MINECO (Ref. CTQ2017-87708-R) and the research support programme of the Seneca Foundation of Science and Technology of Murcia, Spain (Ref. 20977/PI/18). M. G. Montalbán acknowledges support from MINECO (Juan de la Cierva-Formación contract, Ref. FJCI-2016-28081), P. Licence acknowledges EPSRC and BBSRC for support (EP/S005080/1, EP/P013341/1, BB/L013940/1)

Density, refractive index and volumetric properties of water-ionic liquid binary systems with imidazolium-based cations and tetrafluoroborate, triflate and octylsulphate anions at T=293 to 343 K and p=0.1 MPa

©2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical and Engineering Data. To access the final edited and published work see: https://doi.org/10.1021/acs.jced.8b00854The density and refractive index of ionic liquids (ILs) + water binary mixtures were determined as a function of temperature (from 293.15 to 343.15 K) at atmospheric pressure over the whole composition range in which the mixtures were miscible. To carry out a systematic study, all the ILs selected are imidazolium-based ILs with a different number of carbons in the alkyl chain of the cation and also different anions (tetrafluoroborate, triflate and octylsulphate). Specifically, the studied ILs were 1-ethyl-3-methylimidazolium tetrafluoroborate [emim][BF4], 1-butyl-3-methylimidazolium tetrafluoroborate [bmim][BF4], 1-hexyl-3-methylimidazolium tetrafluoroborate [hmim][BF4], 1-methyl-3-octylimidazolium tetrafluoroborate [omim][BF4], 1-ethyl-3-methylimidazolium triflate [emim][TfO], 1-butyl-3-methylimidazolium triflate [bmim][TfO] and 1-butyl-3-methylimidazolium octylsulphate [bmim][OcSO4]. The excess molar volumes and the deviation in the molar refraction of the binary mixtures were calculated for a better understanding of the interactions that take place between the components and successfully correlated by the Redlich-Kister empirical correlations. Bahe-Varela model, which has a more physical meaning, was also used to successfully correlate the excess molar volume values. Volumetric properties, such as apparent molar volumes, partial molar volumes, isobaric thermal expansion coefficients, partial molar volumes at infinite dilution and excess partial molar volumes at infinite dilution were also calculated in order to obtain information about the influence of composition and temperature on the thermodynamic behavior of the selected ILs and water in the mixture. The results are discussed in order to understand the formation of hydrogen bonds between components of the mixture and the possible packing effects that take place in the mixing process. Density and refractive index experimental data were correlated by the Lorentz-Lorenz, Wiener, Dale-Gladstone and Eykman equations to determine the relationship between both parameters, and a good agreement between the experimental and calculated refractive index values was obtained

High pressure phase equilibria for binary mixtures of CO2 + 2-pentanol, vinyl butyrate, 2-pentyl butyrate or butyric acid systems

©2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Supercritical Fluids. To access the final edited and published work see DOI: 10.1021/acs.jced.8b00854High pressure phase equilibrium for four binary systems, (CO2 + 2-pentanol, CO2 + vinyl butyrate, CO2 + 2-pentyl butyrate and CO2 + butyric acid), were measured at three temperatures of (313.15, 323.15 and 333.15) K and pressures up to 11 MPa. These four organic compounds are those involved in the kinetic resolution of rac-2-pentanol and their phase equilibria play a significant role in the separation processes of the reaction compounds. Phase behaviour measurements were taken using a synthetic method in a variable volume high-pressure cell. It was checked that the solubility of CO2 in the four systems decreases with increases in temperature at a constant pressure and all systems present type-I phase behaviour within scope of this work. Modifications of Henry's Law and Peng-Robinson and Soave-Redlich-Kwong equations of state combined with the Quadratic mixing rule were used to correlate experimental equilibrium data to determine the phase behaviour of these systems

Nanoparticles as Drug Delivery Systems

This chapter presents a review on the design of nanoparticles which have been proposed as drug delivery systems in biomedicine. It will begin with a brief historical review of nanotechnology including the most common types of nanoparticles (metal nanoparticles, liposomes, nanocrystals and polymeric nanoparticles) and their advantages as drug delivery systems. These advantages include the mechanism of increased penetration and retention, the transport of insoluble drugs and the controlled release. Next, the nanoparticle design principles and the routes of administration of nanoparticles (parental, oral, pulmonary and transdermal) are discussed. Different routes of elimination of nanoparticles (renal and hepatic) are also analyzed

Silk Fibroin Nanoparticles: Synthesis and Applications as Drug Nanocarriers

The use of nanoparticles in biomedical fields is a very promising scientific area and has aroused the interest of researchers in the search for new biodegradable, biocompatible and non-toxic materials. This chapter is based on the features of the biopolymer silk fibroin and its applications in nanomedicine. Silk fibroin, obtained from the Bombyx mori silkworm, is a natural polymeric biomaterial whose main features are its amphiphilic chemistry, biocompatibility, biodegradability, excellent mechanical properties in various material formats, and processing flexibility. All of these properties make silk fibroin a useful candidate to act as nanocarrier. In this chapter, the structure of silk fibroin, its biocompatibility and degradability are reviewed. In addition, an intensive review on the silk fibroin nanoparticle synthesis methods is also presented. Finally, the application of the silk fibroin nanoparticles for drug delivery acting as nanocarriers is detailed

Effect of Degumming in the Characteristics of Silk Fibroin Nanoparticles

Several studies have stated that the process used for sericin removal, or degumming, from silk cocoons has a strong impact on the silk fibroin integrity and consequently in their mechanical or biochemical properties after processing it into several biomaterials (e.g., fibers, films or scaffolds) but still, there is a lack of information of the impact on the features of silk nanoparticles. In this work, silk cocoons were degummed following four standard methods: autoclaving, short alkaline (Na2CO3) boiling, long alkaline (Na2CO3) boiling, and ultrasounds. The resultant silk fibroin fibers were dissolved in the ionic liquid 1-ethyl-3-methylimidazolium acetate and used for nanoparticle synthesis by rapid desolvation in polar organic solvents. The relative efficiencies of the degumming processes and the integrity of the resulting fibroin fibers obtained were analyzed by mass loss, optical microscopy, thermogravimetric analysis, infrared spectroscopy, and SDS-PAGE. Particle sizes and morphology were analyzed by Dynamic Light Scattering and Field Emission Scanning Electronic Microscopy. The results showed that the different treatments had a remarkable impact on the integrity of the silk fibroin chains, as confirmed by gel electrophoresis, which can be correlated with particle mean size and size distribution changes. The smallest nanoparticles (156 ± 3 nm) and the most negative Z potential (−30.2 ± 1.8 mV) were obtained with the combination of long treatment (2 h) of boiling in alkaline solution (Na2CO3 0.02 eq/L). The study confirms that parameters of the process, such as the composition of the solution and time of the degumming step, must be controlled in order to reach an optimum reproducibility of the nanoparticle production.This work has been partially supported (80%) by the European Commission ERDF/FEDER Operational Programme 'Murcia' CCI N° 2007ES161PO001 (Project No. 14-20/20), and the Spanish MINECO (Ref. CTQ2017-87708-R) and the programme of support to the research of the Seneca Foundation of Science and Technology of Murcia, Spain (Ref. 20977/PI/18). A.A.L.-P.’s research contract was partially supported (80%) by the ERDF/FEDER Operational Programme 'Murcia' CCI N° 2007ES161PO001 (Project No. 14-20/20),. M.G. Montalbán’s research contract is funded by the Spanish MINECO (Juan de la Cierva-Formación contract, Ref. FJCI-2016-28081). S.D.A.-C.’s research contract is funded by the program INIA-CCAA (DOC INIA 2015), announced by the National Institute for Agricultural and Food Research and Technology (INIA) and supported by the Spanish State Research Agency (AEI) under the Spanish Ministry of Economy, Industry and Competitiveness

Antibacterial E ect of Chitosan–Gold Nanoparticles and Computational Modeling of the Interaction between Chitosan and a Lipid Bilayer Model

Pathogenic bacteria have the ability to develop antibiotic resistance mechanisms. Their action consists mainly in the production of bacterial enzymes that inactivate antibiotics or the appearance of modifications that prevent the arrival of the drug at the target point or the alteration of the target point itself, becoming a growing problem for health systems. Chitosan–gold nanoparticles (Cs-AuNPs) have been shown as effective bactericidal materials avoiding damage to human cells. In this work, Cs-AuNPs were synthesized using chitosan as the reducing agent, and a systematic analysis of the influence of the synthesis parameters on the size and zeta potential of the Cs-AuNPs and their UV-vis spectra was carried out. We used a simulation model to characterize the interaction of chitosan with bacterial membranes, using a symmetric charged bilayer and two different chitosan models with different degrees of the chitosan amine protonation as a function of pH, with the aim to elucidate the antibacterial mechanism involving the cell wall disruption. The Cs-AuNP antibacterial activity was evaluated to check the simulation model