Preparation of LDL , Oxidation , Methods of Detection, and Applications in Atherosclerosis Research.

The concept of lipid peroxidation has been known for a long time. It is now well established that LDL plays a major role in atherosclerosis. Oxidized low-density lipoprotein (Ox-LDL) has been studied for over 35 years.

Intestinal and Hepatic Uptake of Dietary Peroxidized Lipids and Their Decomposition Products, and Their Subsequent Effects on Apolipoprotein A1 and Paraoxonase1.

Both pro- and antiatherosclerotic effects have been ascribed to dietary peroxidized lipids. Confusion on the role of peroxidized lipids in atherosclerotic cardiovascular disease is punctuated by a lack of understanding regarding the metabolic fate and potential physiological effects of dietary peroxidized lipids and their decomposition products. This study sought to determine the metabolic fate and physiological ramifications of 13-hydroperoxyoctadecadienoic acid (13-HPODE) and 13-HODE (13-hydroxyoctadecadienoic acid) supplementation in intestinal and hepatic cell lines, as well as any effects resulting from 13-HPODE or 13-HODE degradation products.

Peroxidized Linoleic Acid, 13-HPODE, Alters Gene Expression Profile in Intestinal Epithelial Cells.

Lipid peroxides (LOOHs) abound in processed food and have been implicated in the pathology of diverse diseases including gut, cardiovascular, and cancer diseases. Recently, RNA Sequencing (RNA-seq) has been widely used to profile gene expression. To characterize gene expression and pathway dysregulation upon exposure to peroxidized linoleic acid, we incubated intestinal epithelial cells (Caco-2) with 100 µM of 13-hydroperoxyoctadecadienoic acid (13-HPODE) or linoleic acid (LA) for 24 h.

The dietary peroxidized lipid, 13-HPODE, promotes intestinal inflammation by mediating granzyme B secretion from natural killer cells.

It is well known that consumption of a high-fat diet (HFD) promotes intestinal inflammation despite little being known about causative factors. Recent evidence implicates dietary peroxidized lipids (POLs), which are typically formed from the oxidation of polyunsaturated fatty acid double bonds, as potential contributors due to their enrichment in HFDs, ability to be formed during gastrointestinal transit, and immunogenic and cytotoxic properties. 13-HPODE, the most common dietary POL, demonstrates pro-inflammatory activity in a variety of immune cells, especially Natural Killer (NK) cells whose role in mediating intestinal inflammation remains unclear.

Are Fried Foods Unhealthy? The Dietary Peroxidized Fatty Acid, 13-HPODE, Induces Intestinal Inflammation In Vitro and In Vivo.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder characterized by progressive inflammation and the erosion of the gut mucosa. Although the exact cause of IBD is unknown, multiple factors contribute to its complex pathogenesis. Diet is one such factor and a strong correlation exists between the western-style, high fat diets (HFDs) and IBD incidence rates.

Synthetic Guaiacol Derivatives as Promising Myeloperoxidase Inhibitors Targeting Atherosclerotic Cardiovascular Disease.

Myeloperoxidase (MPO) is known to cause oxidative stress and inflammation leading to cardiovascular disease (CVD) complications. MPO-mediated oxidation of lipoproteins leads to dysfunctional entities altering the landscape of lipoprotein functionality. The specificity of guaiacol derivatives toward preventing MPO-mediated oxidation to limit MPO's harmful effects is unknown.

5F peptide promotes endothelial differentiation of bone marrow stem cells through activation of ERK1/2 signaling.

Synthetic apolipoprotein A-I (apoA-I) mimetic peptide 5F exhibits anti-atherosclerotic ability with largely unknown mechanism(s). Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in vascular integrity and function. The objective of the present study was to evaluate the effect of 5F on endothelial differentiation of BM stem cells and related mechanisms.

Sesamol: a powerful functional food ingredient from sesame oil for cardioprotection.

Phytophenols are important bioactive food based chemical entities, largely present in several natural sources. Among them, sesamol is one of the key natural phenols found in sesame seeds, Piper cubeba etc. Several studies have reported that sesame oil is a potent cardioprotective functional food.

Methoxyphenol derivatives as reversible inhibitors of myeloperoxidase as potential antiatherosclerotic agents.

To evaluate new chemical entities, based on ferulic acid scaffolds, as reversible myeloperoxidase inhibitors (MPOI). docking studies are performed with MPO protein as a target for several ferulic acid analogs followed by multiple assays to validate this approach. Two lead compounds and are identified with optimum docking and IC values: -7.

N-acetylcysteine prevents oxidized low-density lipoprotein-induced reduction of MG53 and enhances MG53 protective effect on bone marrow stem cells.

MG53 is an important membrane repair protein and partially protects bone marrow multipotent adult progenitor cells (MAPCs) against oxidized low-density lipoprotein (ox-LDL). The present study was to test the hypothesis that the limited protective effect of MG53 on MAPCs was due to ox-LDL-induced reduction of MG53. MAPCs were cultured with and without ox-LDL (0-20 μg/mL) for up to 48 hours with or without MG53 and antioxidant N-acetylcysteine (NAC).

Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review.

The intestinal tract is the largest barrier between a person and the environment. In this role, the intestinal tract is responsible not only for absorbing essential dietary nutrients, but also for protecting the host from a variety of ingested toxins and microbes. The intestinal barrier system is composed of a mucus layer, intestinal epithelial cells (IECs), tight junctions (TJs), immune cells, and a gut microbiota, which are all susceptible to external factors such as dietary fats.

Evaluation of Anti-Inflammatory Properties of Herbal Aqueous Extracts and Their Chemical Characterization.

Plant extracts are gaining more attention as therapeutic agents against inflammation. In this study, four different widely used herbals were selected, such as holy basil leaf, sesame seed, long pepper, and cubeb pepper. We have evaluated the anti-inflammatory action of an aqueous extract from these herbs and tested their effects on monocyte-derived macrophages (MDMs).

Cypate and Cypate-Glucosamine as Near-Infrared Fluorescent Probes for In Vivo Tumor Imaging.

Near-infrared (NIR) imaging is a promising technique for use as a noninvasive and sensitive diagnostic tool. Although the NIR fluorescently labeled glucose analog glucosamine (cypate-glucosamine) has applications in preclinical imaging, the transport pathways and fate of this probe in tissues remain unaddressed. Here, we have synthesized and characterized cypate and cypate-glucosamine conjugate (cy-2-glu), and investigated the probable transport pathways of these probes in vitro and in vivo.

Alzheimer's Disease Markers in Aged ApoE-PON1 Deficient Mice.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder associated with aging. Cardiovascular risk factors like hypertension and atherosclerosis increase the risk for AD. Polymorphic alleles of apolipoprotein E (ApoE) are one of the main genetic determinants of AD.

Proinflammatory Properties of Peroxidized Fat May Contribute to the Etiology of Crohn's Disease.

Crohn's disease (CD) is a well-known subset of inflammatory bowel disease (IBD) that results in patchy inflammation through the entire thickness of the bowel wall, with the ability to target virtually any part of the gastrointestinal tract, but most commonly affecting the area between the ileum and the cecum. While a bacterial origin of Crohn's is well speculated, it is difficult to pinpoint what drives inflammation in these subjects, particularly the flare-ups or the sudden symptomatic intensification or recurrence. This review aims at tracing the etiology of CD back to diet, particularly fried foods, a known aggravator of symptoms.

In Situ Immobilized Sesamol-Quinone/Carbon Nanoblack-Based Electrochemical Redox Platform for Efficient Bioelectrocatalytic and Immunosensor Applications.

Most of the common redox mediators such as organic dyes and cyanide ligand-associated metal complex systems that have been used for various electrochemical applications are hazardous nature. Sesamol, a vital nutrient that exists in natural products like sesame seeds and oil, shows several therapeutic benefits including anticancer, antidiabetic, cardiovascular protective properties, etc. Herein, we introduce a new electrochemical redox platform based on a sesamol derivative, sesamol-quinone (Ses-Qn; oxidized sesamol), prepared by the in situ electrochemical oxidation method on a carbon nanoblack chemically modified glassy carbon electrode surface (GCE/CB@Ses-Qn) in pH 7 phosphate buffer solution, for nontoxic and sustainable electrochemical, electroanalytical, and bioelectroanalytical applications.

Primary prevention of atherosclerosis by pretreatment of low-density lipoprotein receptor knockout mice with sesame oil and its aqueous components.

Pharmacological intervention using statins and PCSK9 inhibitors have become first-line therapy in the prevention of hypercholesterolemia and atherosclerosis. Currently, no agent is available for the primary prevention of atherosclerosis. However, there is an emerging hypothesis that atherosclerosis could be driven by inflammation.

Sesame Oil and an Aqueous Extract Derived from Sesame Oil Enhance Regression of Preexisting Atherosclerotic Lesions in Low-Density Lipoprotein Receptor Knockout Mice.

Diet and exercise are recommended both as a prophylactic and as a therapeutic approach for patients with established coronary artery disease. We previously reported that sesame oil (SESO) and its aqueous extract (SOAE) showed antiatherosclerotic and anti-inflammatory properties. We also observed that genes involved in reverse cholesterol transport (RCT) might be activated.

Limiting Dietary Sugar Improves Pediatric Sinonasal Symptoms and Reduces Inflammation.

Excessive sugar consumption is associated with many chronic inflammatory diseases in adults. The effects of excessive sugar consumption in children have not been determined. In this study, we hypothesized that sinonasal symptoms and proinflammatory cytokine levels would be related and could be altered through reduction in sugar-sweetened beverage (SSB) consumption.

Identification and evaluation of anti-inflammatory properties of aqueous components extracted from sesame (Sesamum indicum) oil.

We previously reported that sesame oil (SO) has anti-inflammatory, anti-atherosclerotic and lipid lowering properties in vivo. Our recent studies have shown that, an aqueous extract of sesame oil (SOAE) has also anti-inflammatory and anti-atherosclerotic properties but with no lipid lowering effects. The extent of reduction in atherosclerosis led us to identify components of SOAE and evaluate their anti-inflammatory properties in vitro.

Inflammatory Diseases of the Gut.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract whose prevalence has been dramatically increasing over the past decade. New studies have shown that IBD is the second most common chronic inflammatory disease worldwide after rheumatoid arthritis, affecting millions of people mainly in industrialized countries. Symptoms of IBD include frequent bloody diarrhea, abdominal cramping, anorexia, abdominal distension, and emesis.

Adrenergic hormones induce extrapituitary prolactin gene expression in leukocytes-potential implications in obesity.

The pituitary hormone prolactin (PRL), originally described for its role in lactation, has been implemented in over 300 functions and is produced by multiple cell types outside of the pituitary. Monocyte/macrophages in particular show robust expression of extra-pituitary prolactin (ePRL). While ePRL protein is identical to pituitary PRL and translated from the same gene, tissues outside the pituitary engage an alternative promoter to regulate expression.

A Novel Mechanism for Atherosclerotic Calcification: Potential Resolution of the Oxidation Paradox.

Aim: In this study, we tested the hypothesis that lipid peroxide-derived dicarboxylic acids (DCAs), by virtue of their ability to bind to calcium (Ca), might be involved in atherosclerotic calcification. We determined the ability of azelaic acid (AzA) to promote calcification in human aortic smooth muscle cells (HASMCs), identified AzA in human calcified atherosclerotic lesions, and compared its levels with control and noncalcified atherosclerotic lesions.

Results: HASMCs efficiently converted 9-oxononanoic acid (ONA), a lipid peroxide-derived monocarboxylic aldehyde, to AzA.

Alzheimer's Disease-Current Status and Future Directions.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder of the brain. The presence of amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs), loss of neurons, synapses, and altered sensory perceptions, including memory loss, delineate AD. However, the cause of AD is not clearly known.

Circulating platelet aggregates damage endothelial cells in culture.

Background: Presence of circulating endothelial cells (CECs) in systemic circulation may be an indicator of endothelial damage and/or denudation, and the body's response to repair and revascularization. Thus, we hypothesized that aggregated platelets (AgPlts) can disrupt/denude the endothelium and contribute to the presence of CEC and EC-derived particles (ECDP).

Methods: Endothelial cells were grown in glass tubes and tagged with/without 0.