Quercetin attenuates Pseudomonas aeruginosa-induced acute lung inflammation by inhibiting PI3K/AKT/NF-κB signaling pathway.

Pseudomonas aeruginosa is an opportunistic pathogen that commonly causes infections in immunocompromised individuals with significant morbidity and mortality. Quercetin is a natural flavonoid abundantly present in fruits and vegetables, exerting potent anti-inflammatory effects in treatment of various diseases. However, the molecular mechanisms of quercetin in treatment of P. aeruginosa-induced acute lung inflammation are unclear. In this study, we exploited network pharmacology- and molecular docking-based approach to explore the potential mechanisms of quercetin against P. aeruginosa pneumonia, which was further validated via in vivo and in vitro experiments. The in vivo experiments demonstrated that quercetin alleviated the P. aeruginosa-induced lung injury by diminishing neutrophil infiltration and production of proinflammatory cytokines (IL-1ß, IL-6, and TNF), which was associated with decreased mortality. Moreover, the quercetin-treated mice displayed decreased phosphorylation levels of PI3K, AKT, IκBα, and NF-κB p65 in lung tissues compared to non-drug-treated mice. Similarly, the in vitro study showed that the phosphorylation of these regulatory proteins and production of the proinflammatory cytokines were impaired in the quercetin-pretreated macrophages upon P. aeruginosa infection. Altogether, this study suggested that quercetin reduced the P. aeruginosa-induced acute lung inflammation by suppressing PI3K/AKT/NF-κB signaling pathway.

Liraglutide Enhances the Efficacy of Human Mesenchymal Stem Cells in Preserving Islet ß-cell Function in Severe Non-obese Diabetic Mice.

Glucagon-like peptide 1 (GLP-1) can promote islet ß-cell replication and function, and mesenchymal stem cells (MSCs) can inhibit T cell autoimmunity. This study aimed at testing the dynamic distribution of infused human MSCs and therapeutic effect of combined MSCs and Liraglutide, a long-acting GLP-1 analogue, on preserving ß-cell function in severe non-obese diabetic (NOD) mice. We found that infused MSCs accumulated in the pancreas at 4 weeks post infusion, which was not affected by Liraglutide treatment. Liraglutide significantly enhanced the function of MSCs to preserve islet ß-cells by reducing glucose level at 30 minutes post glucose challenge and increasing the contents and secretion of insulin by islet ß-cells in severe diabetic NOD mice. Infusion with MSCs significantly reduced insulitis scores, but increased the frequency of splenic Tregs, accompanied by reducing the levels of plasma IFN-γ and TNF-α and elevating the levels of plasma IL-10 and transforming growth factor-ß1 (TGF-ß1) in NOD mice. Although Liraglutide mitigated MSC-mediated changes in the frequency of Tregs and the levels of plasma IL-10, Liraglutide significantly increased the levels of plasma TGF-ß1 in severe diabetic NOD mice. Therefore, our findings suggest that Liraglutide may enhance the therapeutic efficacy of MSCs in treatment of severe type 1 diabetes.

Changes in Novel Biomarkers for Protein Oxidation in Pork Patties under Different Cooking Methods.

The aim of this study was to assess the effectiveness of different biomarkers to identify the levels of protein oxidation in pork patties induced by assorted cooking methods. To achieve this purpose, pork patties prepared from longissimus dorsi were cooked using three methods (frying, steaming, and roasting) at different internal temperatures (60, 70, 80, and 90 °C). Traditional biomarkers including total carbonyl and total thiol and novel biomarkers including α-aminoadipic semialdehyde (AAS) and lysinonorleucine (LNL) were determined. Results demonstrated that total thiol and AAS were the most successful biomarkers in distinguishing the three cooking methods in relation to protein oxidation, with AAS being the most sensitive. Moreover, as indicated by the biomarkers of total thiol and AAS, frying caused the highest level of protein oxidation, while steaming resulted in the lowest level when pork patties were cooked to the internal temperatures of 70 or 80 °C.

Protein carbonylation and structural changes in porcine myofibrillar protein exposed to metal ion-H2O2-ascorbate and linoleic acid-lipoxidase oxidizing systems.

The present study aimed to compare two oxidizing systems commonly present in meat for their influence on protein oxidation patterns, with emphasis on the specific lysine-derived markers for protein carbonylation (α-aminoadipic semialdehyde, AAS; lysinonorlucine, LNL) and their relationships with the common markers for protein oxidation. For this purpose, pork myofibrillar proteins (MFP, 5 mg/mL) were suspended in 0.6 M NaCl (pH 7.5) and incubated at 4 ℃ for 24 h with two oxidizing systems: (1) a metal-catalyzed oxidizing system (MOS: 10 µM FeCl3, 100 µM ascorbic acid, and 0-10 mmol/L H2O2), (2) a linoleic acid - lipoxidase oxidizing system (LOS: 7500 units of lipoxidase/mL, and 0-10 mM linoleic acid). Results showed that the amounts of AAS and LNL in both MOS- and LOS-oxidized MFP was proportional to the oxidant concentrations (H2O2 or linoleic acid), while the formation of total carbonyl and total thiol also exhibited similar oxidant-dose-dependent patterns. Meanwhile, the α-helix contents of MFP declined with oxidant concentrations irrespective of the oxidizing systems. The reducing SDS-PAGE revealed that the myosin heavy chain band started to diminish at high H2O2 concentration (5 and 10 mM) in MOS whereas at low level of linoleic acid (0.5 mM) in LOS. Overall, these results demonstrated both oxidizing systems could be involved in the formation of AAS and LNL, and that the generation of AAS and LNL can be used as reliable markers for protein oxidation, but also might be directly involved in protein structural changes and then contribute to the alternations of protein functionality.

Persulfate-based remediation of organic-contaminated soil: Insight into the impacts of natural iron ions and humic acids with complexation/redox functionality.

The use of persulfate (PDS) for in-situ chemical oxidation of organic contaminants in soils has garnered significant interest. However, the presence of naturally occurring iron-containing substances and humic acid (HA) in environmental compartments can potentially influence the effectiveness of soil remediation. Thus, this study aimed to investigate the role of key functional groups (adjacent phenolic hydroxyl (Ar-OH) and carboxyl groups (-COOH)) in HA that interact with iron. Modified HAs were used to confirm the significance of these moieties in iron interaction. Additionally, the mechanism by which specific functional groups affect Fe complexation and redox was explored through contaminant degradation experiments, pH-dependent investigations, HA by-products analysis, and theoretical calculations using six specific hydroxybenzoic acids as HA model compounds. The results showed a strong positive correlation between accessible Ar-OH and -COOH groups and Fe3+/Fe2+ redox. This was attributed to HA undergoing a conversion process to a semiquinone-containing radical form, followed by a quinone-containing intermediate, while Fe3+ acted as an electron shuttle between HA and PDS, with Fe3+ leaching facilitated by generated H+ ions. Although the stability of HA-Fe3+ complexes with -COOH as the primary binding sites was slightly higher at neutral/alkaline conditions compared to acidic conditions, the buffering properties of the soil and acidification of the PDS solution played a greater role in determining the Ar-OH groups as the primary binding site in most cases. Therefore, the availability of Ar-OH groups on HA created a trade-off between accelerated Fe3+/Fe2+ redox and quenching reactions. Appropriate HA and iron contents were found to favor PDS activation, while excessive HA could lead to intense competition for reactive oxygen species (ROS), inhibiting pollutant degradation in soil. The findings provide valuable insights into the interaction of HA and Fe-containing substances in persulfate oxidation, offering useful information for the development of in-situ remediation strategies for organic-contaminated soil.

Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves ß-cell Function in Patients and Non-obese Mice with Severe Diabetes.

Mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for type 1 diabetes (T1D). However, little is known on whether MSC transplantation can benefit T1D patients with ketoacidosis and its potential actions. Here, we show that infusion with bone marrow MSCs preserves ß-cell function in some T1D patients with ketoacidosis by decreasing exogenous insulin requirement and increasing plasma C-peptide levels up to 1-2 years. MSC transplantation increased plasma and islet insulin contents in non-obese diabetic (NOD) mice with severe diabetes. In comparison with severe diabetes controls, MSC infusion reduced insulitis, decreased pancreatic TNF-α, and increased IL-10 and TGF-ß1 expression in NOD mice. MSC infusion increased the percentages of splenic Tregs and levels of plasma IL-4, IL-10 and TGF-ß1, but reduced the percentages of splenic CD8+ T and levels of plasma IFN-γ, TNF-α and IL-17A in NOD mice. Finally, infused MSCs predominantly accumulated in pancreatic tissues at 28 days post infusion. The effects of MSCs on preserving ß-cell function and modulating inflammation tended to be dose-dependent and multiple doses of MSCs held longer effects in NOD mice. Hence, MSC transplantation preserved ß-cell function in T1D patients and NOD mice with severe diabetes by enhancing Treg responses.

[Extracellular polymeric substances disintegration by Fenton oxidation of excess sludge].

Fenton oxidation was used to disintegrate extracellular polymeric substances (EPS) of excess sludge with its strong oxidation ability. The concentration of polysaccharide, protein and the change of soluble chemical oxygen demand (SCOD) disintegrated from EPS represent the EPS disintegration degree. The objective of this study is to optimize the operational conditions for EPS disintegration with Fenton oxidation. It is shown that the optimal operational condition is as following: pH = 2.5, reaction time = 90 min, H2O2/Fe2+ (weight dosage ratio) = 8:1 and reaction temperature is about 65-70 degrees C. Under this condition after the Fenton oxidation, SCOD, concentration of polysaccharide, protein in the supernate increase from 45.88, 10.96 and 11.99 mg x L(-1) to 684.93, 382.17 and 302.62 mg x L(-1), respectively; the average diameter and the median diameter of sludge particulates reduce from 838.89 microm and 859.20 microm to 137.22 microm and 148.69 microm, respectively. As a result, EPS is effectively disintegrated by Fenton oxidation and the sludge is greatly mineralized, which benefits the further sludge reduction and utilization.