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1.
Applications of Innovative Lipidomic Methods for Blood Lipid Biomarkers.
Stark, KD
Journal of oleo science. 2019;(6):503-510
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Abstract
Assessing dietary intake is critical for understanding the relationship between diet and health. Fatty acid blood biomarkers have been particularly useful in determining dietary intakes and assessing the risk of chronic disease. However, fatty acid analysis involves the removal of fatty acids from their complex lipid structures resulting in a loss of potentially useful biological information. "Lipidomics" involves the use of mass spectrometry to identify lipids in their native form. Lipidomic approaches present challenges as an alternative to fatty acid analysis. This includes different types of lipidomic approaches and a lack of consensus on the lipids reported in different studies. Distinguishing between macrolipidomic approaches to characterize highly abundant lipids and microlipidomic approaches examining low abundant bioactive lipids and the use of brutto, medio, genio, and infinio to describe the level of information of lipidomic data can provide clarity to the field. Using lipidomic measurements for understanding docosahexaenoic acid metabolism during pregnancy will also be examined.
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2.
Cholesterol screening and statin use in children: a literature review.
King, K, Macken, A, Blake, O, O'Gorman, CS
Irish journal of medical science. 2019;(1):179-188
Abstract
Atherosclerosis begins in childhood. Fatty streaks, the earliest precursor of atherosclerotic lesions, have been found in the coronary arteries of children of 2 years of age. Hypercholesterolaemia is a risk factor for coronary artery disease. Hypercholesterolaemia can be either primary, when it is characteristic of the main disease, or secondary when it occurs as a result of either a disease process or drug treatment. Given the risk of vascular disease, including myocardial infarction (MI), cerebrovascular accidents (CVA, also known as strokes), peripheral vascular disease (PVD) and ruptured aortic aneurysm, which may follow atherosclerosis, it is important to prevent or slow the early development of atherosclerotic lesions. This prevention necessitates the control of key risk factors such hypercholesterolaemia, dyslipidaemia, hypertension etc. However, at what point this prevention ought to occur, and in what form, is uncertain. Using pharmacological primary prevention for hypercholesterolaemia in the paediatric population is controversial. In an adult patient, hypercholesterolaemia warrants the initiation of a statin. Statins, also known as hydroxymethylglutaryl co-enzyme A inhibitors (or HMG-CoA inhibitors) act by altering cholesterol metabolism. In the paediatric population, the clinical course of vascular disease and the effect of altering this clinical course are less certain. This article reviews the published literature on hypercholesterolaemia in children and the use of statins as a treatment for dyslipidaemia in children. The US National Cholesterol Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents 2012 guidelines (NCEP guidelines) regarding the recognition and treatment of childhood dyslipidaemia are reviewed.
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3.
Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials.
Fogacci, F, Grassi, D, Rizzo, M, Cicero, AFG
Phytotherapy research : PTR. 2019;(4):862-870
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Abstract
The aim of this study is to assess the impact of a combination of berberine and silymarin on serum lipids and fasting plasma glucose (FPG) through a systematic review of literature and meta-analysis of the available randomized, double-blind, placebo-controlled clinical trials (RCTs). A systematic literature search in SCOPUS, PubMed-Medline, ISI Web of Science, and Google Scholar databases was conducted up to October 2, 2018, in order to identify RCTs assessing changes in plasma concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and FPG during treatment with berberine and silymarin in combination. Two review authors independently extracted data on study characteristics, methods, and outcomes. Quantitative data synthesis was performed using a random-effects model. We identified five eligible RCTs, with 497 subjects overall included. Berberine and silymarin combination treatment exerted a positive effect on TC (mean difference [MD]: -25.3, 95% CI [-39.2, -11.4] mg/dl; p < 0.001), TG (MD: -28, 95% CI [-35.3, -20.6] mg/dl; p < 0.001), HDL-C [MD: 6, 95% CI [3.2, 8.8] mg/dl; p < 0.001), LDL-C (MD: -29.1, 95% CI [-39.7, -18.6] mg/dl; p < 0.001), and FPG (MD: -7.5, 95% CI [-13, -1.9] mg/dl; p = 0.008). The present findings suggest that the coadministration of berberine and silymarin is associated with an advantageous improvement in lipid and glucose profile, suggesting the possible use of this nutraceutical combination in order to promote the cardiometabolic health.
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Trials in "True" Dyslipidemic Patients Are Urged to Reconsider Comprehensive Lipid Management as a Means to Reduce Residual Cardiovascular Risk.
Werba, JP, Vigo, LM, Veglia, F, Marenzi, G, Tremoli, E, Baldassarre, D
Clinical pharmacology and therapeutics. 2019;(5):960-967
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Abstract
Randomized cardiovascular trials aimed to reduce the excessive residual risk in high-risk patients through a more aggressive low-density lipoprotein-cholesterol control or targeting triglycerides or high-density lipoprotein-cholesterol levels have shown a null or, at best, limited incremental benefit. In some cases, the treatment produced meaningful effects only in study subgroups. As a consequence, some compounds were withdrawn (e.g., nicotinic acid derivatives and cholesteryl ester transfer protein inhibitors), whereas others (fibrates) are utilized with reluctance due to the low level of evidence-based data. By reviewing these trials analytically, we identified a common feature that might explain their meager results: most of them involved patients generically at high cardiovascular risk with normal or near normal lipid levels and not patients with "true" dyslipidemia, who would receive the treatment if it were part of usual care. These observations may warrant re-examining a central criterion of pragmatism, eligibility, in the outline of forthcoming cardiovascular trials with novel lipid-modifying drugs.
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5.
Metabolic and Vascular Effect of the Mediterranean Diet.
Tuttolomondo, A, Simonetta, I, Daidone, M, Mogavero, A, Ortello, A, Pinto, A
International journal of molecular sciences. 2019;(19)
Abstract
Several studies indicated how dietary patterns that were obtained from nutritional cluster analysis can predict disease risk or mortality. Low-grade chronic inflammation represents a background pathogenetic mechanism linking metabolic risk factors to increased risk of chronic degenerative diseases. A Mediterranean diet (MeDi) style has been reported as associated with a lower degree of inflammation biomarkers and with a protective role on cardiovascular and cerebrovascular events. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. Recently, it has been reported a novel positive association between baseline plasma ceramide concentrations and cardiovascular events and how adherence to a Mediterranean Diet-style may influence the potential negative relationship between elevated plasma ceramide concentrations and cardiovascular diseases (CVD). Several randomized controlled trials (RCTs) showed the positive effects of the MeDi diet style on several cardiovascular risk factors, such as body mass index, waist circumference, blood lipids, blood pressure, inflammatory markers and adhesion molecules, and diabetes and how these advantages of the MeDi are maintained in comparison of a low-fat diet. Some studies reported a positive effect of adherence to a Mediterranean Diet and heart failure incidence, whereas some recent studies, such as the PREDIMED study, showed that the incidence of major cardiovascular events was lower among those assigned to MeDi supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. New studies are needed to better understand the molecular mechanisms, whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases, but also discussing other related diseases. We review MedDiet composition and assessment as well as the latest advances in the genomic, epigenomic (DNA methylation, histone modifications, microRNAs, and other emerging regulators), transcriptomic (selected genes and whole transcriptome), and metabolomic and metagenomic aspects of the MedDiet effects (as a whole and for its most typical food components). We also present a review of the clinical effects of this dietary style underlying the biochemical and molecular effects of the Mediterranean diet. Our purpose is to review the main features of the Mediterranean diet in particular its benefits on human health, underling the anti-inflammatory, anti-oxidant and anti-atherosclerotic effects to which new knowledge about epigenetic and gut-microbiota relationship is recently added.
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Arabidopsis acyl-CoA-binding proteins regulate the synthesis of lipid signals.
Lung, SC, Chye, ML
The New phytologist. 2019;(1):113-117
Abstract
Plant lipid signals are crucial developmental modulators and stress response mediators. A family of acyl-CoA-binding proteins (ACBPs) participates in the lipid trafficking of these signals. Isoform-specific functions can arise from differences in their subcellular distribution, tissue-specificity, stress-responsiveness, and ligand selectivity. In lipid-mediated cell signaling, plant ACBPs are not merely transporters but are also important regulators via their interaction with lipid-metabolic enzymes and precursor lipids. In this Insight, the regulatory roles of plant ACBPs in the synthesis of various signaling lipids, including phosphatidic acid, sterols, oxylipins, and sphingolipids, are reviewed. We focus on the functional significance of these lipid signals in plant development and stress responses with an overview of recent work using reverse genetics and transgenic Arabidopsis.
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Lipid roles in hERG function and interactions with drugs.
Kudaibergenova, M, Perissinotti, LL, Noskov, SY
Neuroscience letters. 2019;:70-77
Abstract
Human-ether-a-go-go-related channel (hERG) is a voltage gated potassium channel (Kv11.1) abundantly expressed in heart and brain tissues. In addition to playing an important role in mediation of repolarizing K+ currents (IKr) in Action Potential (AP), hERG is notorious for its propensity to interact with various medications. The drug-induced block of K+ currents across hERG channel are strongly associated with dysrhythmic conditions collectively known as drug-induced long-QT-syndrome. The recent availability of the high-resolution Cryo-EM structures for the hERG channel has provided unique opportunity to resolve structural mechanisms involved into the process of voltage-gating of hERG channels, map various roles played by components of ventricular and neuronal membranes and then to connect it to cellular pathways through which diverse chemical compounds might be affecting function of the channel. Specifically, lipids and lipid derivatives such as polyunsaturated fatty acids (PUFAs), ceramides and steroids have been shown to directly interact with the lipid facing amino acids in various Kv channels including hERG. In this review, possible lipophilic pathways of hERG activators and blockers, together with the existence of fenestration windows and effects of PUFAs, ceramides and steroids are explored throughout different sections. Finally, the interplay between long QT inducing drugs and phospholipidosis is briefly discussed.
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Lipid profile and risks of cardiovascular diseases in conditions of rheumatoid arthritis.
Pašková, U
Ceska a Slovenska farmacie : casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti. 2019;(6):219-228
Abstract
Cardiovascular diseases (CVD) belong to the leading causes of mortality worldwide. Elevated levels of total cholesterol and LDL cholesterol are associated with increased incidence of CVD in the population. Reversely, reduction of lipoprotein levels in plasma results in a positive impact on CVD prevention. Patients with rheumatoid arthritis (RA), a chronic inflammatory disease, have markedly increased mortality risk due to CVD, despite lower lipoprotein levels in comparison with common population. This is known as the “lipid paradox”. RA itself represents an independent CVD risk factor acting as an inflammatory component. Inflammation, manifested by systemic elevated concentrations of pro-inflammatory cytokines, mainly interleukin 6 (IL-6), interleukin 1β (IL-1β) and the tumour necrosis factor α (TNF-α) in RA, is considered to be the main contributor of atherogenesis via its impact on lipoprotein metabolism and on the biology of the arterial wall. Atherosclerosis, a complex process including a number of mechanisms, is not only regarded as dysregulation of lipid metabolism, but also as a chronic inflammatory disease. This review summarizes the newest findings about the qualitative and quantitative alterations of lipids and lipoproteins affected by low-grade inflammation triggered by RA and their consequences on atherosclerosis.
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Lipid profile differences during menopause: a review with meta-analysis.
Ambikairajah, A, Walsh, E, Cherbuin, N
Menopause (New York, N.Y.). 2019;(11):1327-1333
Abstract
OBJECTIVES The aim of the study was to determine lipid profile differences between premenopausal and postmenopausal women. METHODS The present review used a meta-analytic approach. Sixty-six studies were included, which provided a total sample of 114,655 women consisting of 68,394 that were premenopausal and 46,261 that were postmenopausal. RESULTS The main findings were that (1) lipoproteins were significantly higher in postmenopausal women compared to premenopausal women including triglycerides (0.27 mmol/L, 95% confidence interval, 0.22-0.31), total cholesterol (0.58, 0.50-0.65), low-density lipoprotein (0.45, 0.38-0.53), and total cholesterol to high-density lipoprotein levels (0.39, 0.16-0.62); (2) there was no difference in high-density lipoprotein levels between premenopausal and postmenopausal women (0.02, -0.00-0.04); and (3) the differences in lipid levels was partly attributable to the mean age difference between premenopausal and postmenopausal women. CONCLUSIONS These findings are important as they provide precise estimates of lipid differences in women around menopause. Furthermore the results suggest that the unfavorable lipid profile that develops in postmenopausal women puts them at higher risk of cardiovascular disease such as heart disease and stroke if appropriate lifestyle/pharmacological interventions are not implemented.
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10.
Gene Delivery Using Lipoplexes and Polyplexes: Principles, Limitations and Solutions.
Hayat, SMG, Farahani, N, Safdarian, E, Roointan, A, Sahebkar, A
Critical reviews in eukaryotic gene expression. 2019;(1):29-36
Abstract
Gene therapy has attracted considerable attention for the treatment of genetic and acquired diseases. Successful gene therapy occurs when the therapeutic genes penetrate targeted cells and become available to the intracellular active site. Currently, a promising approach in gene delivery is the use of nonviral gene delivery vectors that lack immunogenicity but have low toxicity and potential tissue specificity. The widely used, existing nonviral gene vectors are cationic lipids and polymers that can pass across extracellular and intracellular barriers. However, the toxicity of these vectors is a barrier to their use. Currently, the disadvantages of nonviral vectors have been minimized by several modifications. The main purpose of this review is to describe the pros and cons of gene delivery using cationic lipids and polymers.