Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdfPeer Reviewe

Contribution of the products of fat hydrolysis to the frothing capacity of milk

The objective of this study was to determine the contribution of the products of lipolysis to milk foaming. Lauric acid and glycerol were added to skim and whole milk at 0.005, 0.010 and 0.015 M lauric acid and 0.011, 0.021 and 0.032 M glycerol. Monoglycerides were added to the milk at the rate of 0.1, 0.2 and 0.3% (m/v) instead of glycerol. Steam frothing value (SFV) of the milk was determined. Other milk samples were also stored for 15 days at 3 0.5 oC and SFV determined after 0, 5, 10 and 15 days. The mean SFV of whole and skim milk decreased on addition of 0.005 M lauric acid. Further increase in FFA did not significantly affect the SFV. The SFV of whole and skim milk decreased on addition of 0.1% monoglycerides. Further increase in monoglycride concentration did not significantly affect the SFV. Glycerol had no effect on the SFV. Storing milk for 15 days at 3oC slightly decrease the SFV of whole milk but increased the SFV of skim milk. This study indicates that monoglycerides and FFA affect milk frothing. Control of milk fat hydrolysis can be used to influence the foaming properties of milk products.Keywords: steam frothing value, fatty acids, monoglycerides, glycerol, foaming, skim milk, whole milkInternational Journal of Agricultural and Rural Development Vol. 5 2004: 114-12

AML with BCR-ABL1 Fusion treated with Imatinib, a Hypomethylating Agent and Venetoclax

A patient with history of myelodysplastic syndrome (MDS) presented with multifocal pneumonia and was found to have Philadelphia chromosomepositive (Ph+) acute myeloid leukemia (AML). A tyrosine kinase inhibitor (TKI) was added to decitabine and venetoclax combination, providing a molecular and cytogenetic complete response despite additional cytogenetic and molecular abnormalities. She remains in remission after eleven cycles of treatment. Our report describes the tolerability and success of a triplet regimen that incorporates a TKI to a backbone of decitabine and venetoclax in a patient with high-risk disease and with significant comorbidities

Quercetin Blocks Airway Epithelial Cell Chemokine Expression

Quercetin (3,3′,4′,5,7-pentahydroxyflavone), a dietary flavonoid, is an inhibitor of phosphatidylinositol (PI) 3-kinase and potent antioxidant. We hypothesized that quercetin blocks airway epithelial cell chemokine expression via PI 3-kinase–dependent mechanisms. Pretreatment with quercetin and the PI 3–kinase inhibitor LY294002 each reduced TNF-α–induced IL-8 and monocyte chemoattractant protein (MCP)-1 (also called CCL2) expression in cultured human airway epithelial cells. Quercetin also inhibited TNF-α–induced PI 3-kinase activity, Akt phosphorylation, intracellular H2O2 production, NF-κB transactivation, IL-8 promoter activity, and steady-state mRNA levels, consistent with the notion that quercetin inhibits chemokine expression by attenuating NF-κB transactivation via a PI 3-kinase/Akt-dependent pathway. Quercetin also reduced TNF-α–induced chemokine secretion in the presence of the transcriptional inhibitor actinomycin D, while inducing phosphorylation of eukaryotic translation initiation factor (eIF)-2α, suggesting that quercetin attenuates chemokine expression by post-transcriptional as well as transcriptional mechanisms. Finally, we tested the effects of quercetin in cockroach antigen–sensitized and –challenged mice. These mice show MCP-1–dependent airways hyperresponsiveness and inflammation. Quercetin significantly reduced lung MCP-1 and methacholine responsiveness. We conclude that quercetin blocks airway cell chemokine expression via transcriptional and post-transcriptional pathways