Compatibility of silorane composite repaired with methacrylate-based restorative systems

The aim of this study was to evaluate the repair bond strength of silorane composites using either the silorane or methacrylate-based restorative systems. Expired silorane composite was used as the substrate material in all experimental groups. Silorane blocks (5?×?5?×?4?mm) were fabricated and stored at 37?°C for 24?h. Six experimental groups were developed according to the repair: I-silorane composite (no intermediary); II-P90 Bond/Silorane; III-P90 Adhesive System (primer/bond)/silorane; IV-P90 bond/Scotchbond Universal/methacrylate composite (Filtek P60); V-Scotchbond Universal/methacrylate; and VI-silane/Adper Single Bond 2/methacrylate. The repaired blocks were stored for 24?h at 37?°C, and then sectioned, yielding stick-shaped specimens (0.5?mm²) that were tested in tensile (0.5?mm/min). The results were analyzed using ANOVA/Tukey test (α?=?0.05). The interfacial micromorphology and nanoleakage were also analyzed under SEM. Scotchbond Universal/methacrylate composite, either associated with the P90 bond or not, exhibited similar bond strength to that of P90 Adhesive System/silorane composite. Scotchbond Universal either associated with the P90 Bond or not to repair the silorane allowed no pre-testing failures. The worst scenarios were repairing the silorane with no intermediary (G-I) or combination silane/Adper Single Bond 2/methacrylate composite (G-VI) that presented significantly lower bond strengths and higher incidences of pre-failure testing. The importance of the silane was not confirmed. Characteristic micromorphology and no signs of nanoleakage were identified in all experimental groups. The silane-containing, phosphorylated methacrylate-based adhesive associated with a methacrylate composite was proven to reliably repair the expired composite in a similar way to that of the application of dedicated silorane adhesive.     

Oxidative and carbonaceous patterning of Si surface in an organic media by scanning probe lithography

A simple top-down fabrication technique that involves scanning probe lithography on Si is presented. The writing procedure consists of a chemically selective patterning in mesitylene. Operating in an organic media is possible to perform local oxidation or solvent decomposition during the same pass by tuning the applied bias. The layer deposited with a positively biased tip with sub-100-nm lateral resolution consists of nanocrystalline graphite, as verified by Raman spectroscopy. The oxide pattern obtained in opposite polarization is later used as a mask for dry etching, showing a remarkable selectivity in SF₆ plasma, to produce Si nanofeatured molds.     

Variations in diffusion coefficient of disperse dyes in single PET fibres: monitored and interpreted by confocal laser scanning microscopy

A novel method is proposed for determining the diffusion coefficient (D) of disperse dyes in PET fibres. Concentration-distance profiles are recorded on optical sections of single fibres by confocal laser scanning microscopy. This allows for an accurate value of the true diffusion coefficient in the fibres as well as for a founded insight in the dye diffusion process and its interrelation with the glass transition, which is not possible by the commonly used methods. At 130 °C, the common industrial dyeing temperature, the diffusion coefficient showed to be constant for the dyes tested, with D being about five times larger for the anthraquinone dye than for the benzodifuranone dye. At 100-110 °C, near to the start of the glass transition region of the fibres, D could no longer be regarded as a constant for the anthraquinone dye but was concentration dependent. This was explained by the plasticising effect of the anthraquinone dye.     

Composition and thermal properties of Rhea oil and its fractions

The rhea (Rhea americana) is a large running bird of the ratite family, native to South America. Oil extracted from rhea fat tissue is used in cosmetic manufacture. Here, the thermal behaviour and the fatty acid and triacylglycerol composition of Uruguayan rhea oil are studied. The results are compared with those obtained from two commercial samples of emu oil. The fatty acid profiles of emu and rhea oils are similar. Small variations are reflected in the non‐identical thermal behaviour of the oils. The solid content of both oils is fairly similar at room temperature. Thus, emu oil and rhea oil may replace one another in certain formulations, without resulting in important changes in physicochemical behaviour. The semisolid rhea oil was fractionated in two successive stages: an olein was obtained at 15 °C, which was refractionated at 10 °C. The thermogram of the olein obtained by cooling at 15 °C does not have the peak found at 34 °C in the thermogram of the original oil and is a softer product than the original oil. A further stage of fractionation of this olein produced a new liquid phase of slightly different thermal behaviour from that of the original olein. This product has a solid fat index around 7% at 15 °C and has melted completely at 20 °C. This second olein has more appropriate physical characteristics than those of the olein obtained from the first fractionation when used in liquid cosmetic formulations.     

Molecular Networking for Drug Toxicities Studies: The Case of Hydroxychloroquine in COVID-19 Patients

Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient’s plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ.     

From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl₂ or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.     

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.     

Activity of Fluorine‐Containing Analogues of WC‐9 and Structurally Related Analogues against Two Intracellular Parasites: Trypanosoma cruzi and Toxoplasma gondii

Two obligate intracellular parasites, Trypanosoma cruzi, the agent of Chagas disease, and Toxoplasma gondii, an agent of toxoplasmosis, upregulate the mevalonate pathway of their host cells upon infection, which suggests that this host pathway could be a potential drug target. In this work, a number of compounds structurally related to WC‐9 (4‐phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, were designed, synthesized, and evaluated for their effect on T. cruzi and T. gondii growth in tissue culture cells. Two fluorine‐containing derivatives, the 3‐(3‐fluorophenoxy)‐ and 3‐(4‐fluorophenoxy)phenoxyethyl thiocyanates, exhibited half‐maximal effective concentration (EC₅₀) values of 1.6 and 4.9 μm , respectively, against tachyzoites of T. gondii, whereas they showed similar potency to WC‐9 against intracellular T. cruzi (EC₅₀ values of 5.4 and 5.7 μm , respectively). In addition, 2‐[3‐ (phenoxy)phenoxyethylthio]ethyl‐1,1‐bisphosphonate, which is a hybrid inhibitor containing 3‐phenoxyphenoxy and bisphosphonate groups, has activity against T. gondii proliferation at sub‐micromolar levels (EC₅₀=0.7 μm ), which suggests a combined inhibitory effect of the two functional groups.     

Multidrug Idebenone/Naproxen Co-loaded Aspasomes for Significant in vivo Anti-inflammatory Activity

The use of proper nanocarriers for dermal and transdermal delivery of anti-inflammatory drugs recently gained several attentions in the scientific community because they pass intact and accumulate payloads in the deepest layers of skin tissue. Ascorbyl palmitate-based vesicles (aspasomes) can be considered a promising nanocarrier for dermal and transdermal delivery due to their skin whitening properties and suitable delivery of payloads through the skin. The aim of this study was the synthesis of multidrug Idebenone/naproxen co-loaded aspasomes for the development of an effective anti-inflammatory nanomedicine. Aspasomes had suitable physicochemical properties and were safe in vivo if topically applied on human healthy volunteers. Idebenone/naproxen co-loaded aspasomes demonstrated an increased therapeutic efficacy of payloads compared to the commercially available Naprosyn® gel, with a rapid decrease of chemical-induced erythema on human volunteers. These promising results strongly suggested a potential application of Idebenone/naproxen multidrug aspasomes for the development of an effective skin anti-inflammatory therapy.     

Measurement of enzymatic activity and specificity of human and avian influenza neuraminidases from whole virus by glycoarray and MALDI-TOF mass spectrometry

Influenza neuraminidases hydrolyze the ketosidic linkage between N-acetylneuraminic acid and its adjacent galactose residue in sialosides. This enzyme is a tetrameric protein that plays a critical role in the release of progeny virions. Several methods have been described for the determination of neuraminidase activity, usually based on colorimetric, fluorescent, or chemiluminescent detection. However, only a few of these tests allow discrimination of the sialyl-linkage specificity (i.e., α2-3- versus α2-6-linked sialyllactosides) of the neuraminidase. Herein we report a glycoarray-based assay and a MALDI-TOF study for assessing the activity and specificity of two influenza neuraminidases on whole viruses. The human A(H3N2) and avian A(H5N2) neuraminidase activities were investigated. The results from both approaches demonstrated that α2-3 sialyllactoside was a better substrate than α2-6 sialyllactoside for both viruses and that H5N2 virus had a lower hydrolytic activity than H3N2.