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Advances have been made in the search for new multi-target modulators to control pain and inflammation. Therefore, compound 3,5-di-tert-butyl-4-hydroxyphenyl)(4-methylpiperazin-1-yl)methanone (LQFM202) was synthesised and evaluated. First, in vitro assays were performed for COX-1, COX-2, and 5-LOX enzymes. Subsequently, adult female Swiss albino mice treated orally with LQFM202 at doses of 25–200 mg/kg were subjected to acetic acid-induced writhing, formalin-induced pain, carrageenan-induced hyperalgesia, carrageenan- or zymosan-induced paw oedema, or pleurisy. LQFM202 inhibited COX-1, COX-2, and LOX-5 (IC50 = 3499 µM, 1565 µM, and 1343 µM, respectively). In acute animal models, LQFM202 (50, 100, or 200 mg/kg) decreased the amount of abdominal writhing (29%, 52% and 48%, respectively). Pain in the second phase of the formalin test was reduced by 46% with intermediate dose. LQFM202 (100 mg/kg) reduced the difference in nociceptive threshold in all 4 h evaluated (46%, 37%, 30%, and 26%, respectively). LQFM202 (50 mg/kg) decreased the carrageenan-oedema from the second hour (27%, 31% and 25%, respectively); however, LQFM202 (100 mg/kg) decreased the carrageenan-oedema in all hours evaluated (35%, 42%, 48% and 50%, respectively). When using zymosan, LQFM202 (50 mg/kg) decreased the oedema in all hours evaluated (33%, 32%, 31% and 20%, respectively). In the carrageenan-pleurisy test, LQFM202 (50 mg/kg) reduced significantly the number of polymorphonuclear cells (34%), the myeloperoxidase activity (53%), TNF-α levels (47%), and IL-1β levels (58.8%). When using zymosan, LQFM202 (50 mg/kg) reduced the number of polymorphonuclear and mononuclear cells (54% and 79%, respectively); and the myeloperoxidase activity (46%). These results suggest antinociceptive and anti-inflammatory effects of LQFM202. [ABSTRACT FROM AUTHOR]

Intranasal administration of mucus-penetrating nanoparticles is an emerging trend to increase drug delivery to the brain. In order to overcome rapid nasal mucociliary clearance, low epithelial permeation, and local enzymatic degradation, we investigated the influence of PEGylation on nose-to-brain delivery of polycaprolactone (PCL) nanoparticles (PCL-NPs) encapsulating bexarotene, a potential neuroprotective compound. PEGylation with 1, 3, 5, and 10% PCL-PEG did not affect particle diameter or morphology. Upon incubation with artificial nasal mucus, only 5 and 10% of PCL-PEG coating were able to ensure NP stability and homogeneity in mucus. Rapid mucus-penetrating ability was observed for 98.8% of PCL-PEG5% NPs and for 99.5% of PCL-PEG10% NPs. Conversely, the motion of non-modified PCL-NPs was markedly slower. Fluorescence microscopy showed that the presence of PEG on NP surface did not reduce their uptake by RMPI 2650 cells. Fluorescence tomography images evidenced higher translocation into the brain for PCL-PEG5% NPs. Bexarotene loaded into PCL-PEG5% NPs resulted in area under the curve in the brain (AUCbrain) 3 and 2-fold higher than that for the drug dispersion and for non-PEGylated NPs (p < 0.05), indicating that approximately 4% of the dose was directly delivered to the brain. Combined, these results indicate that PEGylation of PCL-NPs with PCL-PEG5% is able to reduce NP interactions with the mucus, leading to a more efficient drug delivery to the brain following intranasal administration. [ABSTRACT FROM AUTHOR]

Factors that reduce the quality of common bean during storage, including oxidative rancidity caused by lipoxygenase, have been extensively studied. In this context, this work evaluates lipoxygenase activity in five Carioca bean cultivars at different temperatures and storage times using ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopies. UV absorption analyses demonstrated that the storage temperature of the grains influences the kinetic reaction rates during the enzymatic activity of lipoxygenase. Pinto beans and CNFC 10467 presented lower initial activity than the three BRS varieties but were more sensitive to high temperatures. BRS Estilo presented an anomalous behavior, with a strong reduction in activity at 15 and 21 °C until 72 days of storage. BRSMG Madrepérola and BRS Pontal presented stable enzymatic rates until 108 days of storage. A 26% reduction in fatty acid content, as a result of lipoxygenase action during storage, was observed both in solution-state and high resolution magic angle spinning (HR-MAS) NMR studies. These results highlight the importance of NMR in enzymatic kinetic reactions studies, complementing the results obtained by UV. [ABSTRACT FROM AUTHOR]

In recent years, due to the rapid development of nanotechnology and the desire for breakthroughs in cementitious materials, there has been a strong research focus on the application of nanoparticles as supplementary cementitious materials (SCM) such as nanosilica (NS). This paper investigates the effect of functionalized nanosilica (NSF) with amino groups on Portland cement pastes. Fourier transform infrared (FTIR) spectroscopy, 29Si nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) assays were performed to characterize the NSF and confirm the grafting of the amine organic groups on the nanosilica surface (NS). Samples of cement masses were prepared containing NSF or NS with varying content of 0.3, 0.9 and 2.7% by weight, a reference sample of cement mass was also prepared without any addition. For the characterization of cement pastes, induction calorimetry, mercury intrusion porosimetry, and compressive strength tests were performed. The results showed that NSF samples led to reduced superplasticizer use and decreased hydration rate and that the 0.9% NSF sample achieved compressive strength at 28 days greater than 50 MPa. [ABSTRACT FROM AUTHOR]