Pediatric Brain Tumors: Signatures from the Intact Proteome

The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water–acetonitrile solutions containing proteases inhibitors and analyzed by LC–high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3–22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization.     

Pheomelanin Effect on UVB Radiation-Induced Oxidation/Nitration of l-Tyrosine

Pheomelanin is a natural yellow-reddish sulfur-containing pigment derived from tyrosinase-catalyzed oxidation of tyrosine in presence of cysteine. Generally, the formation of melanin pigments is a protective response against the damaging effects of UV radiation in skin. However, pheomelanin, like other photosensitizing substances, can trigger, following exposure to UV radiation, photochemical reactions capable of modifying and damaging cellular components. The photoproperties of this natural pigment have been studied by analyzing pheomelanin effect on oxidation/nitration of tyrosine induced by UVB radiation at different pH values and in presence of iron ions. Photoproperties of pheomelanin can be modulated by various experimental conditions, ranging from the photoprotection to the triggering of potentially damaging photochemical reactions. The study of the photomodification of l-Tyrosine in the presence of the natural pigment pheomelanin has a special relevance, since this tyrosine oxidation/nitration pathway can potentially occur in vivo in tissues exposed to sunlight and play a role in the mechanisms of tissue damage induced by UV radiation.     

Diagnostic Accuracy of CT Texture Analysis in Adrenal Masses: A Systematic Review

Adrenal incidentalomas (AIs) are incidentally discovered adrenal neoplasms. Overt endocrine secretion (glucocorticoids, mineralocorticoids, and catecholamines) and malignancy (primary or metastatic disease) are assessed at baseline evaluation. Size, lipid content, and washout characterise benign AIs (respectively, <4 cm, <10 Hounsfield unit, and rapid release); nonetheless, 30% of adrenal lesions are not correctly indicated. Recently, image-based texture analysis from computed tomography (CT) may be useful to assess the behaviour of indeterminate adrenal lesions. We performed a systematic review to provide the state-of-the-art of texture analysis in patients with AI. We considered 9 papers (from 70 selected), with a median of 125 patients (range 20–356). Histological confirmation was the most used criteria to differentiate benign from the malignant adrenal mass. Unenhanced or contrast-enhanced data were available in all papers; TexRAD and PyRadiomics were the most used software. Four papers analysed the whole volume, and five considered a region of interest. Different texture features were reported, considering first- and second-order statistics. The pooled median area under the ROC curve in all studies was 0.85, depicting a high diagnostic accuracy, up to 93% in differentiating adrenal adenoma from adrenocortical carcinomas. Despite heterogeneous methodology, texture analysis is a promising diagnostic tool in the first assessment of patients with adrenal lesions.     

Gal3 Plays a Deleterious Role in a Mouse Model of Endotoxemia

Lipopolysaccharide (LPS)-induced endotoxemia induces an acute systemic inflammatory response that mimics some important features of sepsis, the disease with the highest mortality rate worldwide. In this work, we have analyzed a murine model of endotoxemia based on a single intraperitoneal injection of 5 mg/kg of LPS. We took advantage of galectin-3 (Gal3) knockout mice and found that the absence of Gal3 decreased the mortality rate oflethal endotoxemia in the first 80 h after the administration of LPS, along with a reduction in the tissular damage in several organs measured by electron microscopy. Using flow cytometry, we demonstrated that, in control conditions, peripheral immune cells, especially monocytes, exhibited high levels of Gal3, which were early depleted in response to LPS injection, thus suggesting Gal3 release under endotoxemia conditions. However, serum levels of Gal3 early decreased in response to LPS challenge (1 h), an indication that Gal3 may be extravasated to peripheral organs. Indeed, analysis of Gal3 in peripheral organs revealed a robust up-regulation of Gal3 36 h after LPS injection. Taken together, these results demonstrate the important role that Gal3 could play in the development of systemic inflammation, a well-established feature of sepsis, thus opening new and promising therapeutic options for these harmful conditions.     

Coenzyme Q10: Novel Formulations and Medical Trends

The aim of this review is to shed light over the most recent advances in Coenzyme Q₁₀ (CoQ₁₀) applications as well as to provide detailed information about the functions of this versatile molecule, which have proven to be of great interest in the medical field. Traditionally, CoQ₁₀ clinical use was based on its antioxidant properties; however, a wide range of highly interesting alternative functions have recently been discovered. In this line, CoQ₁₀ has shown pain-alleviating properties in fibromyalgia patients, a membrane-stabilizing function, immune system enhancing ability, or a fundamental role for insulin sensitivity, apart from potentially beneficial properties for familial hypercholesterolemia patients. In brief, it shows a remarkable amount of functions in addition to those yet to be discovered. Despite its multiple therapeutic applications, CoQ₁₀ is not commonly prescribed as a drug because of its low oral bioavailability, which compromises its efficacy. Hence, several formulations have been developed to face such inconvenience. These were initially designed as lipid nanoparticles for CoQ₁₀ encapsulation and distribution through biological membranes and eventually evolved towards chemical modifications of the molecule to decrease its hydrophobicity. Some of the most promising formulations will also be discussed in this review.     

Methylene blue adsorption by chemically activated waste pork bones

Bone is an inorganic template containing organic material inside which can be converted into hydroxyapatite‐rich material by pyrolysis. Nowadays, there is a growing research interest in the use of hydroxyapatite, the chemical formula of which is Ca₁₀(PO₄)₆(OH)₂. In the present work, pork bone, an abundant biomass source and food waste, has been converted into structured porous hydroxyapatite by a three‐step process including precharring under mild conditions, chemical activation, and thermal activation. The investigated activating agents were NaOH, KOH, K₂CO₃, H₂SO₄, and H₃PO₄. A thorough investigation of the influence of different activating protocols on the chemical and textural properties of the produced material was carried out by nitrogen adsorption–desorption at 77 K, potentiometric titrations, Fourier transform infrared, and X‐ray diffraction techniques. Chemical activation with NaOH, K₂CO₃, and H₂SO₄ increased the specific surface area up to 53%. H₃PO₄ reduced both surface area and pore volume, and KOH showed little influence on the pore structure. The produced materials were evaluated by methylene blue adsorption tests and showed significant improvement as a result of chemical activation. As a main effect, acid treatment increased methylene blue adsorption kinetics, probably owing to an increase in micropororosity, whereas alkali activation enhanced the adsorption capacity of the resultant biochar.     

Evolution in Structural and Optical Properties of Stannic Oxide Xerogel upon Heat Treatment

Upon consecutive heat treatments at increasing temperatures, the microstructure of solution–sol–gel-derived stannic oxide (SnO₂) xerogel evolves in three stages: (I) below 300°C, characterized by extensive dehydroxylation and gel shrinkage with little grain growth and surface loss; (II) between 300° and 500°C, by extensive crystallization, leading to dramatic surface loss (by 70%); and (III) above 500°C, by grain growth. Concurrently, the UV-absorption edge shows red shifts during stages I and II and blue shifts during stage III, resulting in distinct color variations. The edge displacement bears a close correlation with a Raman "defect band" at ∼305–328 cm⁻¹.     

Facial expression recognition in image sequences using geometric deformation features and Support Vector Machines.

In this paper, two novel methods for facial expression recognition in facial image sequences are presented. The user has to manually place some of Candide grid nodes to face landmarks depicted at the first frame of the image sequence under examination. The grid-tracking and deformation system used, based on deformable models, tracks the grid in consecutive video frames over time, as the facial expression evolves, until the frame that corresponds to the greatest facial expression intensity. The geometrical displacement of certain selected Candide nodes, defined as the difference of the node coordinates between the first and the greatest facial expression intensity frame, is used as an input to a novel multiclass Support Vector Machine (SVM) system of classifiers that are used to recognize either the six basic facial expressions or a set of chosen Facial Action Units (FAUs). The results on the Cohn-Kanade database show a recognition accuracy of 99.7% for facial expression recognition using the proposed multiclass SVMs and 95.1% for facial expression recognition based on FAU detection.