Critical new insights into the interactions of hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) with albumin at molecular and cellular levels.

A key characteristic to be elucidated, to address the harmful health risks of environmental perfluorinated alkyl substances (PFAS), is their binding modes to serum albumin, the most abundant protein in blood. Hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) is a new industrial replacement for the widespread linear long-chain PFAS. However, the detailed interaction of new-generation short-chain PFAS with albumin is still lacking.

(-)-Epigallocatechin gallate as an inhibitor of hemoglobin-catalyzed lipid oxidation: molecular mechanism of action and nutritional application.

Hemoglobin (Hb) is effective inducer for lipid oxidation and protein-polyphenol interaction is a well-known phenomenon. The effects of the interaction of (-)-epigallocatechin gallate (EGCG) with Hb on lipid oxidation were rarely elucidated. The detailed interaction between bovine Hb and EGCG was systematically explored by experimental and theoretical approaches, to illustrate the molecular mechanisms by which EGCG influenced the redox states and stability of Hb.

The interaction of perfluorooctane sulfonate with hemoproteins and its relevance to molecular toxicology.

Perfluorooctane sulfonate (PFOS), a representative of perfluorinated compounds in industrial and commercial products, has posed a great threat to animals and humans via environmental exposure and dietary consumption. Herein, we investigated the effects of PFOS binding on the redox state and stability of two hemoproteins (hemoglobin (Hb) and myoglobin (Mb)). Fluorescence spectroscopy, circular dichroism and UV-vis absorption spectroscopy demonstrated that PFOS could induce the conformational changes of proteins along with the exposure of heme cavity and generation of hemichrome, which resulted in the increased release of free hemin.

Serum albumin acted as an effective carrier to improve the stability of bioactive flavonoid.

The health-improving functions of bioactive flavonoids in vitro and in vivo are often limited by their low stability, which could be counteracted by the application of proteins as carriers of flavonoids. Clarification of the mechanism of protein-ligand interaction is crucial for the encapsulation of bioactive components. Herein, common plasma proteins [i.

Serum albumin mitigated perfluorooctane sulfonate-induced cytotoxicity by affecting the cellular responses.

During the wide applications of perfluorinated materials such as perfluorooctane sulfonate (PFOS) in commercial and industrial products, the potential toxicity of these engineered compounds has attracted more and more attention. As a typical environmental pollutant, PFOS could preferentially bind to albumin protein in vivo. However, the role of protein-PFOS interactions in the cytotoxicity of PFOS was not stressed enough.

Quercetin Attenuates Vascular Endothelial Dysfunction in Atherosclerotic Mice by Inhibiting Myeloperoxidase and NADPH Oxidase Function.

Myeloperoxidase (MPO) exhibits a unique property to use HO to oxidize chloride and lead to the generation of a strong oxidant, hypochlorous acid (HOCl), which plays important roles in atherosclerosis. A lot of evidence indicates that quercetin, a natural polyphenol derived from human diet, effectively contributes to cardiovascular health. Herein, we found that dietary quercetin significantly inhibited vascular endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient (ApoE) mice.

Binding of Quercetin to Hemoglobin Reduced Hemin Release and Lipid Oxidation.

The interactions between quercetin and bovine (or human) hemoglobin (Hb) were systematically investigated by fluorescence, UV-vis absorption spectroscopy, and molecular docking to demonstrate the structural mechanism by which quercetin affected the Hb redox state and stability. Quercetin could interact with the central cavity of the Hb molecule with one binding site to generate an Hb-quercetin complex, and the hydrophobic interaction played an important role in the formation of the complex. The binding constant for the Hb-quercetin complex at 298 K was observed to be 1.

Bovine Serum Albumin as a Potential Carrier for the Protection of Bioactive Quercetin and Inhibition of Cu(II) Toxicity.

Considering the protective ability of proteins and the potential toxicity of free Cu(II), it was proposed herein that the co-presence of protein could play an important role in suppressing the toxicity of free Cu(II) to the stability of bioactive quercetin if a flavonoid-protein-Cu(II) complex could be formed. In this study, the interaction between quercetin (a major flavonoid in the human diet) and bovine serum albumin (BSA) was investigated in the absence and presence of free Cu(II). The results demonstrated that both quercetin and free Cu(II) had a strong ability to quench the intrinsic fluorescence of BSA through a static procedure (i.

Myeloperoxidase Targets Apolipoprotein A-I for Site-Specific Tyrosine Chlorination in Atherosclerotic Lesions and Generates Dysfunctional High-Density Lipoprotein.

We previously demonstrated that apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), is an important target for myeloperoxidase (MPO)-catalyzed tyrosine chlorination in the circulation of subjects with cardiovascular diseases. Oxidation of apoA-I by MPO has been reported to deprive HDL of its protective properties. However, the potential effects of MPO-mediated site-specific tyrosine chlorination of apoA-I on dysfunctional HDL formation and atherosclerosis was unclear.

Generation of a Bovine Serum Albumin-Diligand Complex for the Protection of Bioactive Quercetin and Suppression of Heme Toxicity.

As an abundant protein in milk and blood serum, bovine serum albumin (BSA) contains various sites to bind a lot of bioactive components, generating BSA-monoligand complex. Demonstration of the interaction between BSA and bioactive components (such as heme, flavonoids) is important to develop effective carrier for the protection of bioactive ligands and to reduce cytotoxicity of heme. Herein, the bindings of BSA to quercetin and/or heme were investigated by multispectroscopic and molecular docking methods.

Quercetin Attenuated Myeloperoxidase-Dependent HOCl Generation and Endothelial Dysfunction in Diabetic Vasculature.

Myeloperoxidase (MPO)-dependent hypochlorous acid (HOCl) generation plays crucial roles in diabetic vascular complications. As a natural polyphenol, quercetin has antioxidant properties in various diabetic models. Herein, we investigated the therapeutic mechanism for quercetin on MPO-mediated HOCl generation and endothelial dysfunction in diabetic vasculature.

Quercetin Inhibited Endothelial Dysfunction and Atherosclerosis in Apolipoprotein E-Deficient Mice: Critical Roles for NADPH Oxidase and Heme Oxygenase-1.

NADPH oxidase-dependent superoxide (O) production and oxidative stress play important roles in endothelial dysfunction and atherosclerosis. Herein, we investigated the potential effects of dietary quercetin, a flavonoid derived in the diet from vegetables and fruit, on vascular endothelial function and atherosclerosis in the high-fat diet (HFD)-fed apolipoprotein E-deficient (ApoE) mice. Dietary quercetin treatment significantly suppressed endothelial dysfunction and aortic atherosclerosis in HFD-fed ApoE mice ( < 0.

Dietary nitrate attenuated endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: A critical role for NADPH oxidase.

Nitric oxide (NO) deficiency and NADPH oxidase plays key roles in endothelial dysfunction and atherosclerotic plaque formation. Recent evidence demonstrates that nitrate-nitrite-NO pathway in vivo exerts beneficial effects upon the cardiovascular system. We aimed to investigate the effects of dietary nitrate on endothelial function and atherosclerosis in apolipoprotein E knockout (ApoE) mice fed a high-fat diet.

Phosphine-Free Ru-Catalyzed Regio- and Stereoselective Addition of Benzoic Acids to Trifluoromethylated Alkynes toward Facile Access to Trifluoromethyl Group-Substituted ()-Enol Esters.

A combination of ruthenium catalyst with silver salt and copper salt was proved to be a highly efficient protocol for the direct addition reaction of benzoic acids with unsymmetrical trifluoromethylated internal alkynes. Diverse trifluoromethyl group-substituted ()-enol esters were readily obtained for a broad substrate scope in moderate to good yields with excellent regio- and stereoselectivities under mild reaction conditions.

Supplementation of dietary nitrate attenuated oxidative stress and endothelial dysfunction in diabetic vasculature through inhibition of NADPH oxidase.

The metabolic disorders in diabetes, which are usually accompanied by oxidative stress and impaired nitric oxide (NO) bioavailability, increase the risk of detrimental cardiovascular complications. Herein, we investigated the therapeutic potential of dietary nitrate, which is found in high content in green leafy vegetables, on vascular oxidative stress and endothelial dysfunction in diabetic mice induced by high-fat diet and streptozotocin injection. Dietary nitrate in drinking water fuelled a nitrate-nitrite-NO pathway, which inhibited vascular oxidative stress, endothelial dysfunction and many features of metabolic syndrome in diabetic mice.

Formation of a bovine serum albumin diligand complex with rutin for the suppression of heme toxicity.

Serum albumin binds avidly to heme to form heme-serum albumin complex and can protect against the potentially toxic effects of heme. Rutin is a glycoside of the bioflavonoid quercetin with various protective effects due to its antioxidant ability. Clarification of the interaction mechanisms between serum albumin and bioactive components (such as heme and flavonoid) is important to develop effective carriers for encapsulation of heme and suppression of its toxicity.

Formation of a bovine serum albumin diligand complex with rutin and single-walled carbon nanotubes for the reduction of cytotoxicity.

Carbon nanotubes (CNTs) are extensively used in the area of biotechnology and biomedicine, and the binding of proteins to CNTs plays an important role in the potential toxicity of nanomaterials. Rutin is a glycoside of the bioactive quercetin with various health-improving effects due to its antioxidant ability. Demonstration of the interaction between serum albumin and bioactive components is important to design effective carriers for the suppression of CNTs' toxicity.

Quercetin, but not rutin, attenuated hydrogen peroxide-induced cell damage via heme oxygenase-1 induction in endothelial cells.

Oxidative stress plays an important role in the pathogenesis of cardiovascular disease. Quercetin, a naturally occurring flavonoid presents in plants and human diet, has been reported to exert antioxidant properties in vivo and in vitro. The upregulation of antioxidant enzyme heme oxygenase-1 (HMOX1) in endothelial cells is considered to be beneficial in cardiovascular disease.

Quercetin suppressed NADPH oxidase-derived oxidative stress via heme oxygenase-1 induction in macrophages.

NADPH oxidase-derived superoxide (O) generation and oxidative stress is usually considered as an important factor to the pathogenesis of inflammatory diseases. Quercetin, widely known for their anti-oxidant and anti-inflammatory properties in vitro and in vivo, is recently identified to induce expression of antioxidant enzyme heme oxygenase-1 (HO-1). Previous studies suggest that HO-1 induction and/or subsequent HO-1 end product generation in vitro and in vivo may suppress NADPH oxidase-derived oxidative stress.

NADPH oxidase is a primary target for antioxidant effects by inorganic nitrite in lipopolysaccharide-induced oxidative stress in mice and in macrophage cells.

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and oxidative stress is usually considered as an important factor to the pathogenesis of various diseases. Inorganic nitrite, previously viewed as a harmful substance in our diet or inert metabolites of endogenous NO, is recently identified as an important biological NO reservoir in vasculature and tissues. Stimulation of a nitrite-NO pathway shows organ-protective effects on oxidative stress and inflammation, but the mechanisms or target are not clear.

Iridium-Catalyzed Regioselective Synthesis of Trifluoromethylated Isocoumarins through Annulation of Benzoic Acids with Trifluoromethylated Alkynes.

An unprecedented Ir-catalyzed oxidative coupling of benzoic acids with trifluoromethylated alkynes was successfully developed to provide diverse trifluoromethylated isocoumarins in moderate to good yields. This new practical procedure was highlighted by mild reaction conditions, broad substrate scope, good regioselectivity, high efficiency, and easy operation.

Nitric oxide protected against NADPH oxidase-derived superoxide generation in vascular endothelium: Critical role for heme oxygenase-1.

NADPH oxidase-derived superoxide (O) generation is usually considered as an important factor to the pathogenesis of cardiovascular diseases. Nitric oxide (NO), previously viewed as a key regulator of cardiovascular function, is identified to induce expression of heme oxygenase-1 (HO-1), an antioxidant enzyme in blood vessels. In this study, we tested whether NO might modulate NADPH oxidase activity in vascular endothelium via HO-1.

Adsorption of Plasma Proteins on Single-Walled Carbon Nanotubes Reduced Cytotoxicity and Modulated Neutrophil Activation.

Proteins in the bloodstream bind to carbon nanotubes (CNTs) through noncovalent interactions to form a protein corona, thereby effectively influencing the biological properties and blood biocompatibility of the CNTs. Here, we investigated the binding of common plasma proteins (i.e.

Fibrinogen binding-dependent cytotoxicity and degradation of single-walled carbon nanotubes.

Carbon nanotubes are widely used in the area of biomedicine, and the binding of protein to carbon nanotubes are believed to play an important role in the potential cytotoxicity of nanomaterials. In this work, we investigated the effects of human fibrinogen-surface coatings on the biodegradation and cytotoxicity of carboxylated single-walled carbon nanotubes (SWCNTs). It was found that the electrostatic and π-π stacking interactions might be the crucial factors in stabilizing the binding of fibrinogen with SWCNTs by both theoretical and experimental approaches.