Differential Plasma Metabolites between High- and Low-Grade Meningioma Cases

Meningiomas (MGMs) are currently classified into grades I, II, and III. High-grade tumors are correlated with decreased survival rates and increased recurrence rates. The current grading classification is based on histological criteria and determined only after surgical tumor sampling. This study aimed to identify plasma metabolic alterations in meningiomas of different grades, which would aid surgeons in predefining the ideal surgical strategy. Plasma samples were collected from 51 patients with meningioma and classified into low-grade (LG) (grade I; n = 43), and high-grade (HG) samples (grade II, n = 5; grade III, n = 3). An untargeted metabolomic approach was used to analyze plasma metabolites. Statistical analyses were performed to select differential biomarkers among HG and LG groups. Metabolites were identified using tandem mass spectrometry along with database verification. Five and four differential biomarkers were identified for HG and LG meningiomas, respectively. To evaluate the potential of HG MGM metabolites to differentiate between HG and LG tumors, a receiving operating characteristic curve was constructed, which revealed an area under the curve of 95.7%. This indicates that the five HG MGM metabolites represent metabolic alterations that can differentiate between LG and HG meningiomas. These metabolites may indicate tumor grade even before the appearance of histological features.     

Spectroscopic Characterization and Biological Activity of Hesperetin Schiff Bases and Their Cu(II) Complexes

The three Schiff base ligands, derivatives of hesperetin, HHSB (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]isonicotinohydrazide), HIN (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]benzhydrazide) and HTSC (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]thiosemicarbazide) and their copper complexes, CuHHSB, CuHIN, and CuHTSC were designed, synthesized and analyzed in terms of their spectral characterization and the genotoxic activity. Their structures were established using several methods: elemental analysis, FT-IR, UV-Vis, EPR, and ESI-MS. Spectral data showed that in the acetate complexes the tested Schiff bases act as neutral tridentate ligand coordinating to the copper ion through two oxygen (or oxygen and sulphur) donor atoms and a nitrogen donor atom. EPR measurements indicate that in solution the complexes keep their structures with the ligands remaining bound to copper(II) in a tridentate fashion with (O^–, N, O_ket) or (O^–, N, S) donor set. The genotoxic activity of the compounds was tested against model tumour (HeLa and Caco-2) and normal (LLC-PK1) cell lines. In HeLa cells the genotoxicity for all tested compounds was noticed, for HHSB and CuHHSB was the highest, for HTSC and CuHTSC–the lowest. Generally, Cu complexes displayed lower genotoxicity to HeLa cells than ligands. In the case of Caco-2 cell line HHSB and HTSC induced the strongest breaks to DNA. On the other side, CuHHSB and CuHTSC induced the highest DNA damage against LLC-PK1.     

Genomic and Immunological Characterization of Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Isolates from Northwest Argentina

In recent years, an increase in the prevalence hypermucoviscous carbapenem-resistant Klebsiella pneumoniae with sequence type 25 (ST25) was detected in hospitals of Tucuman (Northwest Argentina). In this work, the virulence and the innate immune response to two K. pneumoniae ST25 strains (LABACER 01 and LABACER 27) were evaluated in a murine model after a respiratory challenge. In addition, comparative genomics was performed with K. pneumoniae LABACER01 and LABACER27 to analyze genes associated with virulence. Both LABACER01 and LABACER27 were detected in the lungs of infected mice two days after the nasal challenge, with LABACER01 counts significantly higher than those of LABACER27. Only LABACER01 was detected in hemocultures. Lactate dehydrogenase (LDH) and albumin levels in bronchoalveolar lavage (BAL) samples were significantly higher in mice challenged with LABACER01 than in LABACER27-infected animals, indicating greater lung tissue damage. Both strains increased the levels of neutrophils, macrophages, TNF-α, IL-1β, IL-6, KC, MCP-1, IFN-γ, and IL-17 in the respiratory tract and blood, with the effect of LABACER01 more marked than that of LABACER27. In contrast, LABACER27 induced higher levels of IL-10 in the respiratory tract than LABACER01. Genomic analysis revealed that K. pneumoniae LABACER01 and LABACER27 possess virulence factors found in other strains that have been shown to be hypervirulent, including genes required for enterobactin (entABCDEF) and salmochelin (iroDE) biosynthesis. In both strains, the genes of toxin–antitoxin systems, as well as regulators of the expression of virulence factors and adhesion genes were also detected. Studies on the genetic potential of multiresistant K. pneumoniae strains as well as their cellular and molecular interactions with the host are of fundamental importance to assess the association of certain virulence factors with the intensity of the inflammatory response. In this sense, this work explored the virulence profile based on genomic and in vivo studies of hypermucoviscous carbapenem-resistant K. pneumoniae ST25 strains, expanding the knowledge of the biology of the emerging ST25 clone in Argentina.     

Sphingolipid Catabolism and Glycerophospholipid Levels Are Altered in Erythrocytes and Plasma from Multiple Sclerosis Patients

Multiple sclerosis (MS) is an autoimmune, inflammatory, degenerative disease of the central nervous system. Changes in lipid metabolism have been suggested to play important roles in MS pathophysiology and progression. In this work we analyzed the lipid composition and sphingolipid-catabolizing enzymes in erythrocytes and plasma from MS patients and healthy controls. We observed reduction of sphingomyelin (SM) and elevation of its products—ceramide (CER) and shingosine (SPH). These changes were supported by the detected up-regulation of the activity of acid sphingomyelinase (ASM) in MS plasma and alkaline ceramidase (ALCER) in erythrocytes from MS patients. In addition, Western blot analysis showed elevated expression of ASM, but not of ALCER. We also compared the ratios between saturated (SAT), unsaturated (UNSAT) and polyunsaturated fatty acids and suggest, based on the significant differences observed for this ratio, that the UNSAT/SAT values could serve as a marker distinguishing erythrocytes and plasma of MS from controls. In conclusion, the application of lipid analysis in the medical practice would contribute to definition of more precise diagnosis, analysis of disease progression, and evaluation of therapeutic strategies. Based on the molecular changes of blood lipids in neurodegenerative pathologies, including MS, clinical lipidomic analytical approaches could become a promising contemporary tool for personalized medicine.     

Methicillin‐Resistant Staphylococcus aureus in Raw Meats and Prepared Foods in Public Hospitals in Salvador,Bahia, Brazil

This study investigated the presence of methicillin‐resistant Staphylococcus aureus (MRSA) in raw meat and fish and foods prepared from them for patient consumption in public hospitals in Salvador, Bahia, in northeastern Brazil. A total of 114 samples of raw meat and fish (chicken, n = 30; beef, n = 30; pork, n = 24; and fish, n = 30) and 63 samples of prepared foods (made with chicken, n = 15; beef, n = 15; pork, n = 15; and fish, n = 18) were collected from the kitchens of 10 different hospitals. Of the 114 investigated raw meat and fish samples, 28.1% were positive for MRSA, which comprised 23.3% beef, 23.3% chicken, 37.5% pork, and 30% fish samples. Of the prepared foods, 9.5% were positive for MRSA, which comprised 5.6% chicken products, 6.7% pork products, and 22.2% fish products. MRSA contamination was not detected in prepared beef dishes. A statistical analysis showed no association between the presence of MRSA and the type of raw food (P > 0.05). The high prevalence of MRSA among the raw foods tested and the presence of the microorganism in prepared foods emphasizes the necessity of enforcing hygienic practices within hospital kitchens.     

Enzymatic de-glycosylation of rutin improves its antioxidant and antiproliferative activities

Bioavailability and biological properties of flavonoid glycosides can be improved after the enzymatic hydrolysis of specific glycosyl groups. In this study, we evaluate the antioxidant and antiproliferative potential of rutin after enzymatic hydrolysis performed by α-l-rhamnosidases (hesperidinase from Penicillium sp. and naringinase from Penicillium decumbens) previously heated at 70 °C for 30 min to inactivate the undesirable β-d-glucosidase activity. The highest in vitro antioxidant activity determined by DPPH radical scavenging was achieved with rutin hydrolyzed by hesperidinase. Rutin was predominantly bioconverted into quercetin-3-glucoside. There was no statistical difference between xanthine oxidase inhibition by rutin before and after hydrolysis. However, in vitro inhibitory activity against ten human tumor cell lines showed that hydrolyzed rutin exerted a more potent antiproliferative effect than quercetin and rutin on various cancer cell lines, specially glioma, and ovarian and breast adenocarcinomas. These results indicate that quercetin-3-glucoside could be a promising functional derivative obtained by rutin hydrolysis.     

Metabolic profile and biological activities of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco: Studies on the essential oil and polar extracts

We investigated the metabolic profile and biological activities of the essential oil and polar extracts of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco collected in south Portugal. Gas chromatography–mass spectrometry (GC–MS) analysis revealed that oxygen-containing monoterpenes was the principal group of compounds identified in the essential oil. Camphor (40.6%) and fenchone (38.0%) were found as the major constituents. High-performance liquid chromatography with diode array detection (HPLC–DAD) analysis allowed the identification of hydroxycinnamic acids (3-O-caffeoylquinic, 4-O-caffeoylquinic, 5-O-caffeoylquinic and rosmarinic acids) and flavones (luteolin and apigenin) in the polar extracts, with rosmarinic acid being the main compound in most of them. The bioactive compounds from L. pedunculata polar extracts were the most efficient free-radical scavengers, Fe²⁺ chelators and inhibitors of malondialdehyde production, while the essential oil was the most active against acetylcholinesterase. Our results reveal that the subspecies of L. pedunculata studied is a potential source of active metabolites with a positive effect on human health.     

Effect of the fungal protease EPg222 on proteolysis and texture in the dry fermented sausage ‘salchichón’

Proteolytic activity of the fungal protease EPg222 and its effect on the texture of the dry fermented sausage ‘salchichón’, which has a long ripening process, was assayed. Samples with enzyme added showed a significant reduction of myofibrillar protein concentration during the ripening period, compared with a control, and proteolytic activity of the enzyme led to a higher accumulation of non‐protein and ‐amino acid nitrogen. Analysis of volatile compounds in ripened dry fermented sausages revealed that only in EPg222 batches were branched compounds derived from amino acids catabolism detected that are associated with the flavour of dry cured meat products. The texture profile analysis showed reduction in hardness, gumminess and chewiness values in treated compared with control sausages. The effect of this enzyme could be of great interest in stimulating proteolysis, in flavour development and in reducing the hardness of dry fermented sausages produced by a long ripening process. Copyright © 2004 Society of Chemical Industry     

A Guide to Polysaccharide-Based Hydrogel Bioinks for 3D Bioprinting Applications

Three-dimensional (3D) bioprinting is an innovative technology in the biomedical field, allowing the fabrication of living constructs through an approach of layer-by-layer deposition of cell-laden inks, the so-called bioinks. An ideal bioink should possess proper mechanical, rheological, chemical, and biological characteristics to ensure high cell viability and the production of tissue constructs with dimensional stability and shape fidelity. Among the several types of bioinks, hydrogels are extremely appealing as they have many similarities with the extracellular matrix, providing a highly hydrated environment for cell proliferation and tunability in terms of mechanical and rheological properties. Hydrogels derived from natural polymers, and polysaccharides, in particular, are an excellent platform to mimic the extracellular matrix, given their low cytotoxicity, high hydrophilicity, and diversity of structures. In fact, polysaccharide-based hydrogels are trendy materials for 3D bioprinting since they are abundant and combine adequate physicochemical and biomimetic features for the development of novel bioinks. Thus, this review portrays the most relevant advances in polysaccharide-based hydrogel bioinks for 3D bioprinting, focusing on the last five years, with emphasis on their properties, advantages, and limitations, considering polysaccharide families classified according to their source, namely from seaweed, higher plants, microbial, and animal (particularly crustaceans) origin.     

Femtosecond-laser selective printing of graphene oxide and PPV on polymeric microstructures

Direct laser writing techniques are suitable for the high precision-patterning of 2D and 3D micro/nanostructures, featuring a variety of geometries and materials. Here, we demonstrated the use of laser-induced forward transfer with fs-pulses (fs-LIFT) to selectively transfer graphene oxide and poly(p-phenylene vinylene) patterns onto polymeric microstructures, fabricated by two-photon polymerization. The influence of different fs-LIFT experimental parameters on the width and height of the printed patterns was investigated. Upon optimum fs-LIFT parameters, we achieved homogeneous printed areas of both materials onto specific regions of the microstructures. Raman spectroscopy confirmed that fs-LIFT does not change the donor material upon transfer. Overall, this work demonstrates a promising strategy with precise printing capabilities, thus opening new opportunities for the development of photonic and optoelectronic devices.