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Inflammation of the adipose tissue plays an important role in the development of several chronic diseases associated with obesity. Polyphenols of extra virgin olive oil (EVOO), such as the secoiridoids oleocanthal (OC) and oleacein (OA), have many nutraceutical proprieties. However, their roles in obesity-associated adipocyte inflammation, the NF-κB pathway and related sub-networks have not been fully elucidated. Here, we investigated impact of OC and OA on the activation of NF-κB and the expression of molecules associated with inflammatory and dysmetabolic responses. To this aim, fully differentiated Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were pre-treated with OC or OA before stimulation with TNF-α. EVOO polyphenols significantly reduced the expression of genes implicated in adipocyte inflammation (IL-1β, COX-2), angiogenesis (VEGF/KDR, MMP-2), oxidative stress (NADPH oxidase), antioxidant enzymes (SOD and GPX), leukocytes chemotaxis and infiltration (MCP-1, CXCL-10, MCS-F), and improved the expression of the anti-inflammatory/metabolic effector PPARγ. Accordingly, miR-155-5p, miR-34a-5p and let-7c-5p, tightly connected with the NF-κB pathway, were deregulated by TNF-α in both cells and exosomes. The miRNA modulation and NF-κB activation by TNF-α was significantly counteracted by EVOO polyphenols. Computational studies suggested a potential direct interaction between OC and NF-κB at the basis of its activity. This study demonstrates that OC and OA counteract adipocyte inflammation attenuating NF-κB activation. Therefore, these compounds could be novel dietary tools for the prevention of inflammatory diseases associated with obesity., Competing Interests: The authors declare no conflict of interest.

Chronic inflammation of the adipose tissue (AT) is a major contributor to obesity-associated cardiometabolic complications. The olive oil polyphenol hydroxytyrosol (HT) contributes to Mediterranean diet cardiometabolic benefits through mechanisms still partially unknown. We investigated HT (1 and 10 μmol/L) effects on gene expression (mRNA and microRNA) related to inflammation induced by 10 ng/mL tumor necrosis factor (TNF)-α in human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. At real-time PCR, HT significantly inhibited TNF-α-induced mRNA levels, of monocyte chemoattractant protein-1, C-X-C Motif Ligand-10, interleukin (IL)-1β, IL-6, vascular endothelial growth factor, plasminogen activator inhibitor-1, cyclooxygenase-2, macrophage colony-stimulating factor, matrix metalloproteinase-2, Cu/Zn superoxide dismutase-1, and glutathione peroxidase, as well as surface expression of intercellular adhesion molecule-1, and reverted the TNF-α-mediated inhibition of endothelial nitric oxide synthase, peroxisome proliferator-activated receptor coactivator-1α, and glucose transporter-4. We found similar effects in adipocytes stimulated by macrophage-conditioned media. Accordingly, HT significantly counteracted miR-155-5p, miR-34a-5p, and let-7c-5p expression in both cells and exosomes, and prevented NF-κB activation and production of reactive oxygen species. HT can therefore modulate adipocyte gene expression profile through mechanisms involving a reduction of oxidative stress and NF-κB inhibition. By such mechanisms, HT may blunt macrophage recruitment and improve AT inflammation, preventing the deregulation of pathways involved in obesity-related diseases.

Atherosclerosis is a dynamic process with inflammatory aspects playing a considerable pathogenetic role. In this process, the vascular endothelium is the key regulator of vascular function, promoting the maintenance of vascular homeostasis or the progression towards vascular disease. In the past 30 years, the dietary intake of omega-3 (n-3) polyunsaturated fatty acids - mainly derived from fish - has emerged as an important way to modify cardiovascular risk through beneficial effects on all stages of atherosclerosis. This review specifically focuses on the modulating effects of n-3 fatty acids on molecular events involved in early and late atherogenesis, including effects on endothelial expression of adhesion molecules, as well as pro-inflammatory and pro-angiogenic enzymes. By accumulating in endothelial membrane phospholipids, omega-3 fatty acids have been shown to decrease the transcriptional activation of several genes through a decreased activation of the nuclear factor-kappaB system of transcription factors. This occurs secondary to decreased generation of intracellular reactive oxygen species. This series of investigations configures a clear example of nutrigenomics, i.e. how nutrients may affect gene expression, ultimately affecting a wide spectrum of human diseases., (Copyright 2007 S. Karger AG, Basel.)

Background: The products of nonenzymatic glycation and oxidation of proteins, the advanced glycation end products (AGEs), form under diverse circumstances such as aging, diabetes, and kidney failure. Recent studies suggested that AGEs may form in inflamed foci, driven by oxidation or the myeloperoxidase pathway. A principal means by which AGEs alter cellular properties is through interaction with their signal-transduction receptor RAGE. We tested the hypothesis that interaction of AGEs with RAGE on endothelial cells enhances vascular activation., Methods and Results: AGEs, RAGE, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin are expressed in an overlapping manner in human inflamed rheumatoid synovia, especially within the endothelium. In primary cultures of human saphenous vein endothelial cells, engagement of RAGE by heterogeneous AGEs or Nepsilon(carboxymethyl)lysine-modified adducts enhanced levels of mRNA and antigen for vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin. AGEs increased adhesion of polymorphonuclear leukocytes to stimulated endothelial cells in a manner reduced on blockade of RAGE., Conclusions: AGEs, through RAGE, may prime proinflammatory mechanisms in endothelial cells, thereby amplifying proinflammatory mechanisms in atherogenesis and chronic inflammatory disorders.

Pulmonary arterial hypertension (PAH) is a rare and progressive disorder that affects the pulmonary vasculature. Although recent developments in pharmacotherapy have extended the life expectancy of PAH patients, their 5‐year survival remains unacceptably low, underscoring the need for multitarget and more comprehensive approaches to managing the disease. This should incorporate not only medical, but also lifestyle interventions, including dietary changes and the use of nutraceutical support. Among these strategies, n‐3 polyunsaturated fatty acids (n‐3 PUFAs) are emerging as promising agents able to counteract the inflammatory component of PAH. In this narrative review, we aim at analysing the preclinical evidence for the impact of n‐3 PUFAs on the pathogenesis and the course of PAH. Although evidence for the role of n‐3 PUFAs deficiencies in the development and progression of PAH in humans is limited, preclinical studies suggest that these dietary components may influence several aspects of the pathobiology of PAH. Further clinical research should test the efficacy of n‐3 PUFAs on top of approved clinical management. These studies will provide evidence on whether n‐3 PUFAs can genuinely serve as a valuable tool to enhance the efficacy of pharmacotherapy in the treatment of PAH. [ABSTRACT FROM AUTHOR]

N-methylpyridinium (NMP) is produced through the pyrolysis of trigonelline during the coffee bean roasting process. Preliminary studies suggest that NMP may have health benefits, thanks to its antioxidant properties. Based on this background, the aim of this study was to evaluate whether NMP could have a protective effect against LPS-induced neuroinflammation in human glioblastoma cells (U87MG). With this aim, U87MG cells were pre-treated with NMP (0.5 μM) for 1 h and then exposed to LPS (1 μg/mL) for 24 h. Our findings show that NMP attenuates LPS-induced neuroinflammation by reducing the expression of pro-inflammatory cytokines, such as IL-1β, TNF-α and IL-6, through the inhibition of the NF-κB signaling pathway, which is critical in regulating inflammatory responses. NMP is able to suppress the activation of the NF-κB signaling pathway, suggesting its potential in preventing neuroinflammatory conditions. These outcomes support the notion that regular consumption of NMP, possibly through coffee consumption, may offer protection against neuroinflammatory states implicated in neurological disorders. [ABSTRACT FROM AUTHOR]

Inflammation of the adipose tissue contributes to the onset and progression of several chronic obesity-related diseases. The two most important lipophilic diterpenoid compounds found in the root of Salvia milthorrhiza Bunge (also called Danshen), tanshinone IIA (TIIA) and cryptotanshinone (CRY), have many favorable pharmacological effects. However, their roles in obesity-associated adipocyte inflammation and related sub-networks have not been fully elucidated. In the present study, we investigated the gene, miRNAs and protein expression profile of prototypical obesity-associated dysfunction markers in inflamed human adipocytes treated with TIIA and CRY. The results showed that TIIA and CRY prevented tumor necrosis factor (TNF)-α induced inflammatory response in adipocytes, by counter-regulating the pattern of secreted cytokines/chemokines associated with adipocyte inflammation (CCL2/MCP-1, CXCL10/IP-10, CCL5/RANTES, CXCL1/GRO-α, IL-6, IL-8, MIF and PAI-1/Serpin E1) via the modulation of gene expression (as demonstrated for CCL2/MCP-1, CXCL10/IP-10, CCL5/RANTES, CXCL1/GRO-α, and IL-8), as well as related miRNA expression (miR-126-3p, miR-223-3p, miR-124-3p, miR-155-5p, and miR-132-3p), and by attenuating monocyte recruitment. This is the first demonstration of a beneficial effect by TIIA and CRY on adipocyte dysfunction associated with obesity development and complications, offering a new outlook for the prevention and/or treatment of metabolic diseases. [ABSTRACT FROM AUTHOR]

In recent years, the consumption of chocolate and, in particular, dark chocolate has been “rehabilitated” due to its high content of cocoa antioxidant polyphenols. Although it is recognized that regular exercise improves energy metabolism and muscle performance, excessive or unaccustomed exercise may induce cell damage and impair muscle function by triggering oxidative stress and tissue inflammation. The aim of this review was to revise the available data from literature on the effects of cocoa polyphenols on exercise-associated tissue damage and impairment of exercise performance. To this aim, PubMed and Web of Science databases were searched with the following keywords: “intervention studies”, “cocoa polyphenols”, “exercise training”, “inflammation”, “oxidative stress”, and “exercise performance”. We selected thirteen randomized clinical trials on cocoa ingestion that involved a total of 200 well-trained athletes. The retrieved data indicate that acute, sub-chronic, and chronic cocoa polyphenol intake may reduce exercise-induced oxidative stress but not inflammation, while mixed results are observed in terms of exercise performance and recovery. The interpretation of available results on the anti-oxidative and anti-inflammatory activities of cocoa polyphenols remains questionable, likely due to the variety of physiological networks involved. Further experimental studies are mandatory to clarify the role of cocoa polyphenol supplementation in exercise-mediated inflammation.

Osteoarthritis (OA) is a joint disease characterized by inflammation of the synovium, angiogenesis, cartilage degradation, and osteophyte formation. Harpagophytum Procumbens DC. ex Meisn., Boswellia Serrata Roxb., Curcuma longa L., Bromelain and Escin (Aesculus hippocastanum) are plants which extracts, together to Bromelain and Escin (Aesculus hippocastanum) are traditionally used in OA. However, their mechanistic role remains unclear. We aimed to investigate whether these bioactives alone or in combination (as in Flonat Fast®) can suppress TNF-α-induced inflammation, angiogenesis, and osteophyte formation using two cell models involved in OA: endothelial cells and monocytes. Each plant extract was evaluated for its polyphenol content, antioxidant activity, and toxicity. In endothelial cells and monocytes, expression of genes involved in OA was assessed, functional assays for inflammation and angiogenesis were performed, and impairment of reactive oxygen species production (ROS) was evaluated. Exposure of cells to the bioactives alone and in combination before cytokine stimulation resulted in differential counterregulation of several gene and protein expressions, including those for cyclooxygenases-2, metalloproteinase-9, transforming growth factor β1, and bone morphogenic protein-2. We demonstrated that these bioactives modulated monocyte adhesion to endothelial cells as well as cell migration and endothelial angiogenesis. Consistent with radical scavenging activity in the cell-free system, the bioactives curbed TNF-α-stimulated intracellular ROS production. We confirmed the potential anti-inflammatory and antiangiogenic effects of the combination of Harpagophytum procumbens, Boswellia, Curcuma, Bromelain, and Escin and provided new mechanistic evidence for their use in OA. However, further clinical studies are needed to evaluate the true clinical utility of these bioactives as supportive, preventive, and therapeutic agents. [ABSTRACT FROM AUTHOR]

This review collects and critically examines data on the levels of tumour necrosis factor-alpha (TNF-α) in lean, overweight and obese subjects, and the effects of intervention with different foods and food products containing bioactive constituents in overweight/obese individuals. We additionally explore the influence of different single nucleotide polymorphisms (SNPs) on TNF-α levels and compare the response to food products with that to some anti-obesity drugs. Our aim was to provide an overview of the variability, consistency, and magnitude of the reported effects of dietary factors on TNF-α, and to envisage the reliability of measuring changes in the levels of this cytokine as a biomarker responsive to food intervention in association with the reduction in body weight. Regarding the circulating levels of TNF-α, we report: (i) a large intra-group variability, with most coefficients of variation (CV%) values being ≥30% and, in many cases, >100%; (ii) a large between-studies variability, with baseline TNF-α values ranging from <1.0 up to several hundred pg/mL; (iii) highly variable effects of the different dietary approaches with both statistically significant and not significant decreases or increases of the protein, and the absolute effect size varying from <0.1 pg/mL up to ≈50 pg/mL. Within this scenario of variability, it was not possible to discern clear differentiating limits in TNF-α between lean, overweight, and obese individuals or a distinct downregulatory effect on this cytokine by any of the different dietary approaches reviewed, i.e., polyunsaturated fatty acids (PUFAs), Vitamin-D (VitD), mixed (micro)nutrients, (poly)phenols or other phytochemicals. Further, there was not a clear relationship between the TNF-α responses and body weight changes. We found similarities between dietary and pharmacological treatments in terms of variability and limited evidence of the TNF-α response. Different factors that contribute to this variability are discussed and some specific recommendations are proposed to reinforce the need to improve future studies looking at this cytokine as a potential biomarker of response to dietary approaches. [ABSTRACT FROM AUTHOR]

Pathogenetically characterized by the absence of celiac disease and wheat allergy, non-celiac gluten sensitivity (NCGS) is a clinical entity triggered by the consumption of gluten-containing foods that relieved by a gluten-free diet. Since it is very difficult to maintain a complete gluten-free diet, there is a high interest in discovering alternative strategies aimed at reducing gluten concentration or mitigating its toxic effects. Plant-based dietary models are usually rich in bioactive compounds, such as polyphenols, recognized to prevent, delay, or even reverse chronic diseases, including intestinal disorders. However, research on the role of polyphenols in mitigating the toxicity of gluten-containing foods is currently limited. We address the metabolic fate of dietary polyphenols, both as free and bound macromolecule-linked forms, with particular reference to the gastrointestinal compartment, where the concentration of polyphenols can reach high levels. We analyze the potential targets of polyphenols including the gluten peptide bioavailability, the dysfunction of the intestinal epithelial barrier, intestinal immune response, oxidative stress and inflammation, and dysbiosis. Overall, this review provides an updated overview of the effects of polyphenols as possible dietary strategies to counteract the toxic effects of gluten, potentially resulting in the improved quality of life of patients with gluten-related disorders. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to evaluate the vascular health properties of extracts from biofortified bread, obtained by adding different durum wheat milling by-products rich in phenolic compounds, by analyzing their effects on overwhelming inflammatory response in endothelial cells and monocytes, two main players of atherogenesis. Methods: Human umbilical vein endothelial cells or U937 monocytes were incubated with increasing concentrations (1, 5, 10 μg/mL) of biofortified bread polyphenol extracts or corresponding pure phenolic acids before stimulation with lipopolysaccharide (LPS). We analyzed the endothelial-monocyte adhesion and related endothelial adhesion molecules. The expression of chemokines and pro-inflammatory cytokines was also measured in LPS-stimulated endothelial cells and monocytes as well as intracellular oxidative stress. Results: Biofortified bread extracts inhibited monocyte adhesion to LPS-stimulated endothelial cells, in a concentration-dependent manner by reducing mainly endothelial VCAM-1 expression. Phenolic acid extracts contained in 10 mg biofortified bread downregulated the LPS-induced expression of chemokines MCP-1, M-CSF, and CXCL-10 as well as pro-inflammatory cytokines TNF-α and IL-1β, in endothelial cells and monocytes, with CXCL-10 as the most reduced inflammatory mediator. Among phenolic acids of biofortified bread, ferulic, sinapic, and p-coumaric acids significantly inhibited the LPS-stimulated CXCL-10 expression in vascular cells. The reduced pro-inflammatory response was related to a slightly but significant reduction of intracellular oxidative stress. Conclusions: Our findings suggest the bread biofortified with selected durum wheat milling by-products as a source of phenolic acids with multiple anti-inflammatory and anti-atherosclerotic properties, which could help to counteract or prevent inflammatory vascular diseases. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Adipose tissue inflammation is a mechanistic link between obesity and its related sequelae, including insulin resistance and type 2 diabetes. Dual ligands of peroxisome proliferator activated receptor (PPAR)α and γ, combining in a single molecule the metabolic and inflammatory-regulatory properties of α and γ agonists, have been proposed as a promising therapeutic strategy to antagonize adipose tissue inflammation. Here we investigated the effects of the dual PPARα/γ agonist aleglitazar on human adipocytes challenged with inflammatory stimuli. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were treated with aleglitazar or – for comparison – the selective agonists for PPARα or γ fenofibrate or rosiglitazone, respectively, for 24 h before stimulation with TNF-α. Aleglitazar, at concentrations as low as 10 nmol/L, providing the half-maximal transcriptional activation of both PPARα and PPARγ, reduced the stimulated expression of several pro-inflammatory mediators including interleukin (IL)-6, the chemokine CXC-L10, and monocyte chemoattractant protein (MCP)-1. Correspondingly, media from adipocytes treated with aleglitazar reduced monocyte migration, consistent with suppression of MCP-1 secretion. Under the same conditions, aleglitazar also reversed the TNF-α-mediated suppression of insulin-stimulated ser473 Akt phosphorylation and decreased the TNF-α-induced ser312 IRS1 phosphorylation, two major switches in insulin-mediated metabolic activities, restoring glucose uptake in insulin-resistant adipocytes. Such effects were similar to those obtainable with a combination of single PPARα and γ agonists. In conclusion, aleglitazar reduces inflammatory activation and dysfunction in insulin signaling in activated adipocytes, properties that may benefit diabetic and obese patients. The effect of aleglitazar was consistent with dual PPARα and γ agonism, but with no evidence of synergism. [ABSTRACT FROM AUTHOR]

Abstract: Iodinated radiocontrast media have been the most widely used pharmaceuticals for intravascular administration in diagnostic and interventional angiographic procedures. Although they are regarded as relatively safe drugs and vascular biocompatibility of contrast media has been progressively improved, severe adverse reactions may occur, among which acute nephropathy is one of the most clinically significant complications after intravascular administration of contrast media and a powerful predictor of poor early and long-term outcomes. Since radiocontrast media are given through the arterial or the venous circulation in vascular procedures, morphological and functional changes of the microvascular and macrovascular endothelial cells substantially contribute to the pathogenesis of organ-specific and systemic adverse reactions of contrast media. Endothelial toxicity of contrast media seems to be the result of both direct proapoptotic effects and morphological derangements, as well as endothelial dysfunction and induction of inflammation, oxidative stress, thrombosis, and altered vasomotor balance, with predominant vasoconstrictive response in atherosclerotic coronary arteries and kidney microcirculation. Further understanding of pathogenetic mechanisms underlying contrast media-induced adverse reactions in cellular targets, including endothelial cells, will hopefully lead to the development of novel preventive strategies appropriately curbing the pathogenesis of contrast media vasotoxicity. [Copyright &y& Elsevier]

Vascular inflammation, especially at the level of endothelial cells, has been shown to play a pivotal role in the inception, progression, and clinical complications of atherosclerosis. The common denominators for the activation of inflammatory genes appear to be a small subset of transcription factors-among which include nuclear factor-κB, activator protein-1 (AP-1), and GATA-that function as the central hub of vascular inflammation. Strategies directed to inhibit both the secondary mediators and the primary triggers (atherosclerosis risk factors) appear viable to inhibit atherosclerosis. However, attempts have now been made to address the central hub of vascular inflammation. 'Old' drugs, such as dipyridamole, can also now be revisited for properties related to inhibition of vascular inflammation, probably by acting on the common hub of inflammation. [ABSTRACT FROM AUTHOR]

Aims: Cyclooxygenase (COX)-2 expression is increased in inflammation and angiogenesis and also in atherosclerotic plaques, where it co-localizes with metalloproteinases (MMPs) involved in the fibrous cap weakening. Insight into the regulation of COX-2 and MMP-9 expression suggests the involvement of a Rho-dependent pathway. Because statins interfere with Rho activation, we investigated the statin effect on COX-2 and MMP expressions in the human endothelium. [ABSTRACT FROM PUBLISHER]

Although coffee consumption has been historically associated with negative health outcomes, recent evidence suggests a lower risk of metabolic syndrome, obesity and diabetes among regular coffee drinkers. Among the plethora of minor organic compounds assessed as potential mediators of coffee health benefits, trigonelline and its pyrolysis product N-methylpyridinium (NMP) were preliminary shown to promote glucose uptake and exert anti-adipogenic properties. Against this background, we aimed at characterizing the effects of trigonelline and NMP in inflamed and dysfunctional human adipocytes. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were treated with NMP or, for comparison, trigonelline, for 5 h before stimulation with tumor necrosis factor (TNF)-α. NMP at concentrations as low as 1 µmol/L reduced the stimulated expression of several pro-inflammatory mediators, including C-C Motif chemokine ligand (CCL)-2, C-X-C Motif chemokine ligand (CXCL)-10, and intercellular adhesion Molecule (ICAM)-1, but left the induction of prostaglandin G/H synthase (PTGS)2, interleukin (IL)-1β, and colony stimulating factor (CSF)1 unaffected. Furthermore, NMP restored the downregulated expression of adiponectin (ADIPOQ). These effects were functionally associated with downregulation of the adhesion of monocytes to inflamed adipocytes. Under the same conditions, NMP also reversed the TNF-α-mediated suppression of insulin-stimulated Ser473 Akt phosphorylation and attenuated the induction of TNF-α-stimulated lipolysis restoring cell fat content. In an attempt to preliminarily explore the underlying mechanisms of its action, we show that NMP restores the expression of the master regulator of adipocyte differentiation peroxisome proliferator-activated receptor (PPAR)γ and downregulates activation of the pro-inflammatory mitogen-activated protein jun N-terminal kinase (JNK). In conclusion, NMP reduces adipose dysfunction in pro-inflammatory activated adipocytes. These data suggest that bioactive NMP in coffee may improve the inflammatory and dysmetabolic milieu associated with obesity. [ABSTRACT FROM AUTHOR]

Hyperhomocysteinemia is a recognized risk factor for vascular disease, but pathogenetic mechanisms involved in its vascular actions are largely unknown. Because VCAM-1 expression is crucial in monocyte adhesion and early atherogenesis, we evaluated the NF-κB-related induction of VCAM-1 by homocysteine (Hcy) and the possible inhibitory effect of dietary polyphenolic antioxidants, such as trans-resveratrol (RSV) and hydroxytyrosol (HT), which are known inhibitors of NF-κB-mediated VCAM-1 induction. In human umbilical vein endothelial cells (HUVEC), Hcy, at 100 μmol/l, but not cysteine, induced VCAM-1 expression at the protein and mRNA levels, as shown by enzyme immunoassay and Northern analysis, respectively. Transfection studies with deletional VCAM-1 promoter constructs demonstrated that the two tandem NF-κB motifs in the VCAM-1 promoter are necessary for Hcy-induced VCAM-1 gene expression. Hcy-induced NF-κB activation was confirmed by EMSA, as shown by the nuclear translocation of its p65 (RelA) subunit and the degradation of the inhibitors IκB-α and IKB-β by Western analysis. Hcy also increased intracellular reactive oxygen species by NAD(P)H oxidase activation, as shown by the membrane translocation of its p47phox subunit. NF-κB inhibitors decreased Hcy-induced intracellular reactive oxygen species and VCAM-1 expression. Finally, we found that nutritionally relevant concentrations of RSV and HT, but not folate and vitamin B6, reduce (by <60% at 10-6 mol/l) Hcy-induced VCAM-1 expression and monocytoid cell adhesion to the endothelium. These data indicate that pathophysiologically relevant Hcy concentrations induce VCAM-1 expression through a prooxidant mechanism involving NF-κB. Natural Mediterranean diet antioxidants can inhibit such activation, suggesting their possible therapeutic role in Hcy-induced vascular damage. [ABSTRACT FROM AUTHOR]

Chronic stress is known to influence dietary choices, and stressed families often report poorer diet quality; however, little is known about how family-based stress is linked with dietary patterns that promote inflammation. This study investigated associations between family-based stress and the inflammatory potential of the diet among preschool-aged children and their parents. Parents (n = 212 mothers, n = 146 fathers) and children (n = 130 girls, n = 123 boys; aged 18 months to 5 years) from 241 families participating in the Guelph Family Health Study were included in the analyses. Parents reported levels of parenting distress, depressive symptoms, household chaos, and family functioning. The inflammatory potential of parents' and children's diets was quantified using the Dietary Inflammatory Index (DII®), adjusted for total energy intake (i.e., the E-DIITM). E-DII scores were regressed onto family stress using generalized estimating equations to account for shared variance among family clusters. Compared to those in homes with low chaos, parents in chaotic homes had significantly more proinflammatory dietary profiles (β = 0.973; 95% CI: 0.321, 1.624, p = 0.003). Similarly, compared to those in well-functioning families, parents in dysfunctional families had significantly more proinflammatory dietary profiles (β = 0.967; 95% CI: 0.173, 1.761, p = 0.02). No significant associations were found between parents' E-DII scores and parenting distress or depressive symptoms, nor were any associations found for children's E-DII scores. Results were not found to differ between males and females. Parents in chaotic or dysfunctional family environments may be at increased risk of chronic disease due to proinflammatory dietary profiles. Children's dietary inflammatory profiles were not directly associated with family stress; however, indirect connections through family food-related behaviours may exist. Future research should prioritize elucidating these mechanisms. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide and a growing healthcare problem. Identification of modifiable risk factors for prevention and treatment of COPD is urgent, and the scientific community has begun to pay close attention to diet as an integral part of COPD management, from prevention to treatment. This review summarizes the evidence from observational and clinical studies regarding the impact of nutrients and dietary patterns on lung function and COPD development, progression, and outcomes, with highlights on potential mechanisms of action. Several dietary options can be considered in terms of COPD prevention and/or progression. Although definitive data are lacking, the available scientific evidence indicates that some foods and nutrients, especially those nutraceuticals endowed with antioxidant and anti-inflammatory properties and when consumed in combinations in the form of balanced dietary patterns, are associated with better pulmonary function, less lung function decline, and reduced risk of COPD. Knowledge of dietary influences on COPD may provide health professionals with an evidence-based lifestyle approach to better counsel patients toward improved pulmonary health. [ABSTRACT FROM AUTHOR]

The article discusses the paper by Xu et al. that shows the relation of phthalates to abnormal fetal development. It mentions that exposure to di-2-ethylhexyl phthalate induces or potentiates an intrauterine inflammatory response. However, it also notes that maternal supplementation of anti-inflammatory agent very-long-chain n-3 polyunsaturated fatty acids (PUFAs) can possibly counteract the effects of phthalate exposure.

Abstract: Objective: Hydroxytyrosol (HT), the major olive oil antioxidant polyphenol in cardioprotective Mediterranean diets, is endowed with anti-inflammatory and anti-atherosclerotic activity. The production of cyclooxygenase (COX)-2-dependent inflammatory eicosanoids and the functionally linked release of matrix metalloproteinase (MMP)-9 by macrophages likely contribute to plaque instability leading to acute coronary events. Objective of the study was to examine the HT effects on inflammatory markers in human activated monocytes, including MMP-9 and COX-2 activity and expression and explore HT underlying mechanisms. Methods and results: Human peripheral blood mononuclear cells (PBMC) and U937 monocytes were treated with 1–10 μmol/L HT before activation with phorbol myristate acetate (PMA). HT blunted monocyte matrix invasive potential and reduced MMP-9 release and expression at zymography, ELISA and RT-PCR, with an IC50 = 10 μmol/L ( P< 0.05), without affecting tissue inhibitor of metalloproteinase (TIMP)-1. Moreover, HT inhibited prostaglandin (PG)E2 production and COX-2 expression, without affecting COX-1. These effects were mediated by inhibition of transcription factor nuclear factor (NF)-κB and protein kinase C (PKC)α and PKCβ1 activation. Conclusion: HT, at nutritionally relevant concentrations, reduces MMP-9 and COX-2 induction in activated human monocytes via PKCα and PKCβ1 inhibition, thus featuring novel anti-inflammatory properties. Overall, such results contribute to explaining the vascular protective effects by olive oil polyphenols in Mediterranean diets. [Copyright &y& Elsevier]

Abstract: Diets with high content of antioxidant polyphenols are associated with low prevalence of cardiovascular diseases and cancer. Inflammatory angiogenesis is a key pathogenic process both in cancer and atherosclerosis, and is tightly regulated by the proinflammatory enzyme cyclooxygenase (COX)-2 and the matrix degrading enzymes matrix metalloproteinases (MMPs). We studied the effects of antioxidant polyphenols from virgin olive oil (oleuropein and hydroxytyrosol) and red wine (resveratrol and quercetin) on endothelial cell angiogenic response in vitro, and explored underlying mechanisms. Cultured endothelial cells were pre-incubated with 0.1–50μmol/L polyphenols before stimulation with phorbol myristate acetate (PMA). All tested polyphenols reduced endothelial cell tube formation on matrigel and migration in wound healing assays. The reduced angiogenesis was associated with the inhibition of PMA-induced COX-2 protein expression and prostanoid production, as well as MMP-9 protein release and gelatinolytic activity. These effects were accompanied by a significant reduction in the stimulated intracellular reactive oxygen species levels and in the activation of the redox-sensitive transcription factor nuclear factor (NF)-κB. Our findings reveal that olive oil and red wine polyphenols reduce inflammatory angiogenesis in cultured endothelial cells, through MMP-9 and COX-2 inhibition, supporting a potential protective role for dietary polyphenols in atherosclerotic vascular disease and cancer. [Copyright &y& Elsevier]

Aortic stenosis (AS) is a dynamic degenerative process that shares many pathophysiological features with atherogenesis, from initial proinflammatory calcification and focal thickening of the valve leaflets to obstruction of left ventricular outflow due to superimposed of severe calcification and immobilization of the valve leaflets. As the prevalence increases with age, AS is expected to become one of the most common heart diseases worldwide. In both obese and nonobese patients, persistent thickening of epicardial adipose tissue (EAT) is associated with a shift in its normal metabolic functions toward a dysmetabolic and proatherogenic phenotype that may impair the physiology of adjacent coronary arteries and promote the occurrence of coronary atherosclerosis. In tight analogy with atherosclerosis, recent clinical evidence indicates that EAT may also exert a deleterious role in promoting AS and contributing to myocardial dysfunction, leading to increased health risk for elderly patients with AS and an economic burden on the health care system. This review discusses the clinical and pathologic evidence for the association between EAT and AS and concomitant left ventricular hypertrophy, and provides new insights for the future direction of AS diagnosis and treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

The lower occurrence of cardiovascular disease and cancer in populations around the Mediterranean basin as detected in the 1950s was correctly attributed to the peculiar dietary habits of those populations. Essentially, until the mid-20th century, typical Mediterranean diets were rich in fruits, vegetables, legumes, whole-wheat bread, nuts, fish, and, as a common culinary trait, the routine use of extra-virgin olive oil. Nowadays, the regular adoption of such dietary patterns is still thought to result in healthful benefits. Such patterns ensure the assumption of molecules with antioxidant and anti-inflammatory actions, among which ω-3 polyunsaturated fatty acids (PUFAs), ω-9 monounsaturated fatty acids (oleic acid), and phenolic compounds. The aim of this review is to provide an update of the vasculo-protective pathways mediated by ω-3 PUFAs and polyphenols in the context of the modern Mediterranean dietary habits, including the possible cross-talk and synergy between these typical components. This review complements a parallel one focusing on the role of dietary nitrates and alimentary fats. [ABSTRACT FROM AUTHOR]