Metabolic Profiling of VOCs Emitted by Bacteria Isolated from Pressure Ulcers and Treated with Different Concentrations of Bio-AgNPs

Considering the advent of antibiotic resistance, the study of bacterial metabolic behavior stimulated by novel antimicrobial agents becomes a relevant tool to elucidate involved adaptive pathways. Profiling of volatile metabolites was performed to monitor alterations of bacterial metabolism induced by biosynthesized silver nanoparticles (bio-AgNPs). Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis were isolated from pressure ulcers, and their cultures were prepared in the presence/absence of bio-AgNPs at 12.5, 25 and 50 µg mL⁻¹. Headspace solid phase microextraction associated to gas chromatography–mass spectrometry was the employed analytical platform. At the lower concentration level, the agent promoted positive modulation of products of fermentation routes and bioactive volatiles, indicating an attempt of bacteria to adapt to an ongoing suppression of cellular respiration. Augmented response of aldehydes and other possible products of lipid oxidative cleavage was noticed for increasing levels of bio-AgNPs. The greatest concentration of agent caused a reduction of 44 to 80% in the variety of compounds found in the control samples. Pathway analysis indicated overall inhibition of amino acids and fatty acids routes. The present assessment may provide a deeper understanding of molecular mechanisms of bio-AgNPs and how the metabolic response of bacteria is untangled.     

Cyclooxygenase Inhibition Alters Proliferative,Migratory, and Invasive Properties of Human Glioblastoma Cells In Vitro

Prostaglandin E₂ (PGE₂) is known to increase glioblastoma (GBM) cell proliferation and migration while cyclooxygenase (COX) inhibition decreases proliferation and migration. The present study investigated the effects of COX inhibitors and PGE₂ receptor antagonists on GBM cell biology. Cells were grown with inhibitors and dose response, viable cell counting, flow cytometry, cell migration, gene expression, Western blotting, and gelatin zymography studies were performed. The stimulatory effects of PGE₂ and the inhibitory effects of ibuprofen (IBP) were confirmed in GBM cells. The EP2 and EP4 receptors were identified as important mediators of the actions of PGE₂ in GBM cells. The concomitant inhibition of EP2 and EP4 caused a significant decrease in cell migration which was not reverted by exogenous PGE₂. In T98G cells exogenous PGE₂ increased latent MMP2 gelatinolytic activity. The inhibition of COX1 or COX2 caused significant alterations in MMP2 expression and gelatinolytic activity in GBM cells. These findings provide further evidence for the importance of PGE₂ signalling through the EP2 and the EP4 receptor in the control of GBM cell biology. They also support the hypothesis that a relationship exists between COX1 and MMP2 in GBM cells which merits further investigation as a novel therapeutic target for drug development.     

Two-step sinter-crystallization of K2O–CaO–P2O5–SiO2 (45S5-K) bioactive glass

Bioactive glasses and glass-ceramics (GCs) effectively regenerate bone tissue, however most GCs show improved mechanical properties. In this work, we developed and tested a rarely studied bioactive glass composition (24.4K₂O-26.9CaO-46.1SiO₂-2.6P₂O₅ mol%, identified as 45S5-K) with different particle sizes and heating rates to obtain a sintered GC that combines good fracture strength, low elastic modulus, and bioactivity. We analyzed the influence of the sintering processing conditions in the elastic modulus, Vickers microhardness, density, and crystal phase formation in the GC. The best GC shows improved properties compared with its parent glass. This glass achieves a good densification degree with a two-step viscous flow sintering approach and the resulting GC shows as high bioactivity as that of the standard 45S5 Bioglass®. Furthermore, the GC elastic modulus (56 GPa) is relatively low, minimizing stress shielding. Therefore, we unveiled the glass sintering behavior with concurrent crystallization of this complex bioactive glass composition and developed a potential GC for bone regeneration.     

7-Amidocoumarins as Multitarget Agents against Neurodegenerative Diseases: Substitution Pattern Modulation

This study explores the potential of 7-amidocoumarins as multitarget agents against Parkinson's and Alzheimer's diseases, by modulating the substitution patterns within the scaffold. Sixteen compounds were synthesized via 7-amino-4-methylcoumarin acylation, and in vitro evaluation of the molecules against hMAO-A, hMAO-B, hAChE, hBuChE and hBACE1 was performed. Five compounds turned out to be potent and selective hMAO-B inhibitors in the nanomolar range, six displayed inhibitory activity of hMAO-A in the low micromolar range, one showed hAChE inhibitory activity and another one hBACE1 inhibitory activity. MAO-B reversibility profile of 7-(4’-chlorobenzamido)-4-methylcoumarin ( 10 ) was investigated, with this compound being a reversible inhibitor. Neurotoxicity on motor cortex neurons and neuroprotection against H₂O₂ were also studied, corroborating the safety profile of these molecules. Finally, theoretical ADME properties were also calculated, showing these molecules as good candidates for the optimization of a lead compound. Results suggest that by modulating the substitution pattern at position 7 of the scaffold, selective or multitarget molecules can be achieved.     

Environmental impact estimation of ceramic lightweight aggregates production starting from residues

Within a circular economy approach, this study investigates the environmental impact of lightweight aggregates (LWAs) produced starting from different mixes of different clays with brewery sludge and cattle bone flour ash (CBA), used as poring and fertilizing agents, respectively. The environmental impact was evaluated by means of release tests, insulation capacity, carbon footprint (CFP), and particulate matter emission during pellet firing. Release tests representative of LWAs realistic application showed very high release of phosphate and satisfactory release of potassium. The thermal insulation of the LWAs was tested by thermal imaging camera and resulted highly variable depending on the composition, with the mix containing CBA performing best. This latter composition leads also to the smallest CO₂ equivalent emission, due to the calorific power of CBA, allowing lower consumption of fossil fuels during the LWA production. Finally, total particulate emissions during the thermal treatment resulted similar in terms of mass for all mixes, while differences in terms of particle morphology and composition occurred. Samples containing residue resulted with a quite good release behavior, CFP, and insulation properties, but higher emission of particles, particularly when glass is added.     

The circular economy of agro and post-consumer residues as raw materials for sustainable ceramics

The circular economy in the area of waste management implies their re-use as a raw material in different production cycles. Both the qualitative and quantitative characteristics of the residues from the agro sector and those of the products of the ceramics sector make possible to think of a feasible application. This review will illustrate some examples of recycling of residues deriving from animal and vegetable sectors (and two post consume products, spent coffee grounds, and packaging glass cullet), studied by the authors, falling within the concept of urban and agricultural sustainable development. Not only the most traditional products such as glass-ceramics, glazes, bricks, but also the most innovative lightweight aggregates for plant structures or in and out soil cultivation, as well as additives such as deflocculants for ceramic suspensions, which will be illustrated from the design/production, characterization, and comparison with commercial products.     

Piperacillin/tazobactam‐induced neurotoxicity in a hemodialysis patient: A case report

Antibiotics are potentially a cause of neurotoxicity in dialysis patients, the most common are the beta‐lactams as ceftazidime and cefepime, and few cases have been reported after piperacillin/tazobactam use. This report presents a case of a hypertensive and diabetic 67‐year‐old woman in regular hemodialysis, which previously had a stroke. She was hospitalized presenting pneumonia, which was initially treated with cefepime. Two days after treatment, she presented dysarthria, left hemiparesis, ataxia, and IX and X cranial nerves paresis. Computed tomography showed no acute lesions and cefepime neurotoxicity was hypothesized, and the antibiotic was replaced by piperacillin/tazobactam. The neurologic signs disappeared; however, 4 days after with piperacillin/tazobactam treatment, the neurological manifestations returned. A new computed tomography showed no new lesions, and the second antibiotic regimen withdrawn. After two hemodialysis sessions, the patient completely recovered from neurological manifestations. The patient presented sequentially neurotoxicity caused by two beta‐lactams antibiotics. This report meant to alert clinicians that these antibiotics have dangerous neurological effects in chronic kidney disease patients.