Zinc(II)-methimazole complexes: synthesis and reactivity

The tetrahedral S-coordinated complex [Zn(MeImHS)(4)](ClO4)(2), synthesised from the reaction of [Zn(ClO4)(2)] with methimazole (1-methyl-3H-imidazole-2-thione, MeImHS), reacts with triethylamine to yield the homoleptic complex [Zn(MeImS)(2)] (MeImS = anion methimazole). ESI-MS and MAS C-13-NMR experiments supported MeImS acting as a (N, S)-chelating ligand. The DFT-optimised structure of [Zn(MeImS)(2)] is also reported and the main bond lengths compared to those of related Zn-methimazole complexes. The complex [Zn(MeImS)(2)] reacts under mild conditions with methyl iodide and separates the novel complex [Zn(MeImSMe)(2)I-2] (MeImSMe = S-methylmethimazole). X-ray diffraction analysis of the complex shows a ZnI2N2 core, with the methyl thioethers uncoordinated to zinc. Conversely, the reaction of [Zn( MeImS)(2)] with hydroiodic acid led to the formation of the complex [Zn(MeImHS)(2)I-2] having a ZnI2S2 core with the neutral methimazole units S-coordinating the metal centre. The Zn-coordinated methimazole can markedly modify the coordination environment when changing from its thione to thionate form and vice versa. The study of the interaction of the drug methimazole with the complex [Zn(MeIm)(4)](2+) (MeIm = 1-methylimidazole) - as a model for Zn-enzymes containing a N-4 donor set from histidine residues shows that methimazole displaces only one of the coordinated MeIm molecules; the formation constant of the mixed complex [Zn(MeIm)(3)(MeImHS)](2+) was determined

Social norms and problematic gaming among adolescents: The role of Internet use coping motives.

Problematic gaming (PG) is a public health issue among adolescents worldwide. Although several studies have documented that peer influences constitute a relevant risk factor for adolescent problematic behaviors, little research is currently available on PG. The aim of this study was to examine the contribution of social norms and perceived friends' gaming frequency on participants' own gaming frequency and PG, by testing potential differences among groups with low vs. high motive to use the Internet (e.g., online gaming) as a coping strategy. A survey was administered to 470 adolescent gamers (mean age = 15.49 years; SD = 1.05 years; 77.9 % males). A theoretical model was tested through path analysis and multi-group comparisons were performed. Path analysis revealed that social norms and perceived friends' gaming frequency were positively associated to participants' gaming behaviors and PG. Additionally, different patterns between groups emerged. Our findings confirmed the relative importance of peer influences on adolescents' gaming behaviors and PG and showed that adolescents who rely more on online gaming to cope with negative affect may be more vulnerable to social influence processes than other peers. These findings may provide useful indications for prevention programs targeting adolescent PG. [Abstract copyright: Copyright © 2023 Elsevier Ltd. All rights reserved.

In Vitro Screening

This research was funded by Fundação para a Ciência e a Tecnologia (FCT-MCTES), Radiation Biology and the Biophysics Doctoral Training Programme (RaBBiT, PD/00193/2012); the scholarship grant number PD/BD/142829/2018, to T.P.P. from the RaBBiT Doctoral Training Programme. Publisher Copyright: © 2023 by the authors.Photodynamic therapy is a minimally invasive procedure used in the treatment of several diseases, including some types of cancer. It is based on photosensitizer molecules, which, in the presence of oxygen and light, lead to the formation of reactive oxygen species (ROS) and consequent cell death. The selection of the photosensitizer molecule is important for the therapy efficiency; therefore, many molecules such as dyes, natural products and metallic complexes have been investigated regarding their photosensitizing potential. In this work, the phototoxic potential of the DNA-intercalating molecules—the dyes methylene blue (MB), acridine orange (AO) and gentian violet (GV); the natural products curcumin (CUR), quercetin (QT) and epigallocatechin gallate (EGCG); and the chelating compounds neocuproine (NEO), 1,10-phenanthroline (PHE) and 2,2′-bipyridyl (BIPY)—were analyzed. The cytotoxicity of these chemicals was tested in vitro in non-cancer keratinocytes (HaCaT) and squamous cell carcinoma (MET1) cell lines. A phototoxicity assay and the detection of intracellular ROS were performed in MET1 cells. Results revealed that the IC50 values of the dyes and curcumin in MET1 cells were lower than 30 µM, while the values for the natural products QT and EGCG and the chelating agents BIPY and PHE were higher than 100 µM. The IC50 of MB and AO was greatly affected by irradiation when submitted to 640 nm and 457 nm light sources, respectively. ROS detection was more evident for cells treated with AO at low concentrations. In studies with the melanoma cell line WM983b, cells were more resistant to MB and AO and presented slightly higher IC50 values, in line with the results of the phototoxicity assays. This study reveals that many molecules can act as photosensitizers, but the effect depends on the cell line and the concentration of the chemical. Finally, significant photosensitizing activity of acridine orange at low concentrations and moderate light doses was demonstrated.publishersversionpublishe

Nanoparticle systems for cancer phototherapy: An overview

465687/2014-8). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Photodynamic therapy (PDT) and photothermal therapy (PTT) are photo-mediated treatments with different mechanisms of action that can be addressed for cancer treatment. Both phototherapies are highly successful and barely or non-invasive types of treatment that have gained attention in the past few years. The death of cancer cells because of the application of these therapies is caused by the formation of reactive oxygen species, that leads to oxidative stress for the case of photodynamic therapy and the generation of heat for the case of photothermal therapies. The advancement of nanotechnology allowed significant benefit to these therapies using nanoparticles, allowing both tuning of the process and an increase of effectiveness. The encapsulation of drugs, development of the most different organic and inorganic nanoparticles as well as the possibility of surfaces’ functionalization are some strategies used to combine phototherapy and nanotechnology, with the aim of an effective treatment with minimal side effects. This article presents an overview on the use of nanostructures in association with phototherapy, in the view of cancer treatment.publishersversionpublishe

Gravimetry and petrophysics in the Chad basin area: determination of the basement depth and the implication for defining a scientific drilling site (ICDP-CHADRILL project)

The Chad basin is a huge intracratonic sag-basin (2.5 million km2) in the North Central Africa. In this work, we investigated the basement depth under the Chad Lake using the inversion of gravity residual data obtained by the regression analysis between gravity and topography data. It has been carried on with a collaboration between the University of Trieste and the Institut de Physique du Globe, Strasbourg (IPGS) in order to contribute to the decision of the location of a ICDP drilling site (Bol, SE Chad Lake). This project consists in a compared analysis between gravity data with other geological/geophysical data and their interpretation in terms of tectonic features. The main objectives of this work are: (1) estimation of the basement depth under the Chad basin through a joint analysis and interpretation of satellite and terrestrial gravity data (GOCE, BGI) [1] with borehole data and density values of Cameroon-Chadian rock samples. (2) Estimation and interpretation of the Bouguer and residual gravity anomalies. The results obtained gave us information about the basement depth and the thickness of sediment infill of the basin. Observing the residual values of gravity anomaly field we found a large negative anomaly (-30 mGal) under the Chad basin connected to the presence of low-density sediments. Furthermore, there are several positive anomalies around the edges of the basin [3] and a pattern of linear negative anomalies outside of it. Both types of trends are linked to the presence of rifts and extensional structures. Using the inversion modelling, we could observe a deepening variation of the depth of the basement moving from the southern part (2-3 km) to the northern (4-6 km) one of the Chad Lake. The deepening of the basement is connected to the Termit rift basin and the values are consistent with previous seismic surveys [2]. The depth of the basement under the city of Bol is between 3 and 4 km, but unfortunately, there are no other geological/geophysical constraints to confirm these values. For the drilling purpose, since in the inversion we used a minimum value of the density contrast (200 kg/m3) among the range defined (200-400 kg/m3), it is possible to assume that the maximum expected depth of the basement is about 4 km. We suggest an integrative geophysical survey, such as a seismic reflection campaign to get more detailed information about the structure of the basement (faults, highs and lows) as well as on the variability of its depth and the thickness of the sediment cover

Multivariate calibration approach for quantitative determination of cell-line cross contamination by intact cell mass spectrometry and artificial neural networks

Cross-contamination of eukaryotic cell lines used in biomedical research represents a highly relevant problem. Analysis of repetitive DNA sequences, such as Short Tandem Repeats (STR), or Simple Sequence Repeats (SSR), is a widely accepted, simple, and commercially available technique to authenticate cell lines. However, it provides only qualitative information that depends on the extent of reference databases for interpretation. In this work, we developed and validated a rapid and routinely applicable method for evaluation of cell culture cross-contamination levels based on mass spectrometric fingerprints of intact mammalian cells coupled with artificial neural networks (ANNs). We used human embryonic stem cells (hESCs) contaminated by either mouse embryonic stem cells (mESCs) or mouse embryonic fibroblasts (MEFs) as a model. We determined the contamination level using a mass spectra database of known calibration mixtures that served as training input for an ANN. The ANN was then capable of correct quantification of the level of contamination of hESCs by mESCs or MEFs. We demonstrate that MS analysis, when linked to proper mathematical instruments, is a tangible tool for unraveling and quantifying heterogeneity in cell cultures. The analysis is applicable in routine scenarios for cell authentication and/or cell phenotyping in general

Role of extracellular matrix in gastrointestinal cancer-associated angiogenesis

Gastrointestinal tumors are responsible for more cancer-related fatalities than any other type of tumors, and colorectal and gastric malignancies account for a large part of these diseases. Thus, there is an urgent need to develop new therapeutic approaches to improve the patients\u2019 outcome and the tumor microenvironment is a promising arena for the development of such treatments. In fact, the nature of the microenvironment in the different gastrointestinal tracts may significantly influence not only tumor development but also the therapy response. In particular, an important microenvironmental component and a potential therapeutic target is the vasculature. In this context, the extracellular matrix is a key component exerting an active effect in all the hallmarks of cancer, including angiogenesis. Here, we summarized the current knowledge on the role of extracellular matrix in affecting endothelial cell function and intratumoral vascularization in the context of colorectal and gastric cancer. The extracellular matrix acts both directly on endothelial cells and indirectly through its remodeling and the consequent release of growth factors. We envision that a deeper understanding of the role of extracellular matrix and of its remodeling during cancer progression is of chief importance for the development of new, more efficacious, targeted therapies