Glycated α-lactalbumin based micelles for quercetin delivery: Physicochemical stability and fate of simulated digestion.

Glycated protein is a kind of promising material that can improve the bioavailability of bioactive compounds and achieve sustained release under digestion. In this study, the α-lactalbumin (ALA)-dextran conjugates synthesized by Maillard reaction were fabricated to load and protect quercetin. Quercetin-loaded micelles stabilized by the ALA-dextran conjugates 1:4 showed the smallest size (428.57 ± 5.64 nm) with highest encapsulation efficiency (94.38% ± 0.50%) of quercetin. Compared to ALA/dextran mixture complex, the conjugates-based micelles had better pH, ionic strength and photothermal stability. Furthermore, the micelles composed of the conjugates 1:2 and 1:4 showed the best controlled release effect during the simulated digestion, releasing 62.41% and 66.15% of quercetin from the total encapsulated contents, respectively, which was mainly related to the resistance of glycated ALA to the enzymes. The findings indicated that ALA-dextran conjugates could be effectively designed for the ideal delivery system of hydrophobic bioactive compounds in food industry.

miR-155 promotes macrophage pyroptosis induced by Porphyromonas gingivalis through regulating the NLRP3 inflammasome.

OBJECTIVE: The aim of this study is to detect pyroptosis in macrophages stimulated with Porphyromonas gingivalis and elucidate the mechanism by which P. gingivalis induces pyroptosis in macrophages. METHODS: The immortalized human monocyte cell line U937 was stimulated with P. gingivalis W83. Flow cytometry was carried out to detect pyroptosis in macrophages. The expression of miR-155 was detected by real-time PCR and inhibited using RNAi. Suppressor of cytokine signaling (SOCS) 1, cleaved GSDMD, caspase (CAS)-1, caspase-11, apoptosis-associated speck-like protein (ASC), and NOD-like receptor protein 3 (NLRP3) were detected by Western blotting, and IL-1ß and IL-18 were detected by ELISA. RESULTS: The rate of pyroptosis in macrophages and the expression of miR-155 increased upon stimulation with P. gingivalis and pyroptosis rate decreased when miR-155 was silenced. GSDMD-NT, CAS-11, CAS-1, ASC, NLRP3, IL-1ß, and IL-18 levels increased, but SOCS1 decreased in U937 cells after stimulated with P. gingivalis. These changes were weakened in P. gingivalis-stimulated U937 macrophages transfected with lentiviruses carrying miR-155 shRNA compared to those transfected with non-targeting control sequence. However, there was no significant difference in ASC expression between P. gingivalis-stimulated shCont and shMiR-155 cells. CONCLUSIONS: Porphyromonas gingivalis promotes pyroptosis in macrophages during early infection. miR-155 is involved in this process through regulating the NLRP3 inflammasome.

Degradation Characteristics of a Novel PAF Receptor Antagonist, SY0916, in Aqueous Solution.

SY0916 has been proven to be a potent treatment agent against rheumatoid arthritis in preclinical studies and has been shown to be safe in phase I clinical trials. However, SY0916 is unstable in water, which is frequently used in pharmaceutical development processes. The degradation behaviour and stability of SY0916 in aqueous solutions were investigated at different pH levels, periods of time, and temperatures. Two degradation products (DPs) were successfully separated and characterized by liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS/MS), liquid chromatography coupled to nuclear magnetic resonance with solid phase extraction (LC-SPE-NMR), and nuclear magnetic resonance (NMR). SY0916 decomposed to its α,ß-unsaturated ketone in protonic solvents, and the α,ß-unsaturated ketone further transformed into its alcohol form through a conjugate addition reaction in aqueous media. The results of this study indicate that the pH of the buffer solutions should be maintained between 3.0 and 3.6 for maximum SY0916 stability. Factors that affect degradation should be carefully controlled to mitigate or avoid drug decay.