1,721,038 research outputs found

    ω-3 PUFAs, why are we speaking of them?

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    In spite of the fact that few dietary components are so widely recognized as able to improve human health such as ω-3 polyunsaturated fatty acids (PUFAs), so that their sector in the nutritional market has been increasingly growing worldwide, many unresolved questions still remain about them. In particular there is urgent need for better understanding their possible role as anti-neoplastic agents. First of all, the chemical structure, the intracellular metabolism and the dietary sources and bioavailability of these dietary fatty acids will be described in this introductive chapter to make easier the comprehension of the remaining parts of the book. Afterwards, a brief outline of ω-3 PUFA reported benefits in different fields of human health will be provided. In this introductive part we will tackle also the problem of the discrepancies occurring between the results of most experimental studies on animals and cultured cells, which, almost univocally, suggest the beneficial anti-neoplastic effects of these fatty acids, and the outcome of several of the epidemiological observational studies, which, conversely, show a scarce or null positive association between high intake of fish or fish oil at high content in ω-3 PUFAs and prevention of different kinds of cancer. Finally, a brief outline of the organization of the present book will be provided

    ω-3 PUFAs and colon cancer: experimental studies and human interventional trials

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    Colon cancer represents one of the most frequent forms of cancer worldwide. There is plenty of evidence to support the notion that chemoprevention is a major component of colon cancer control, and that dietary fats influence the rate of incidence of this kind of cancer. In particular, a variety of experimental studies conducted on animals subject to chemical carcinogenesis of colon, transplanted with colon cancer cells, or representing a genetic model of colon cancer, have demonstrated the ability of diets at high content of ω-3 polyunsaturated fatty acids (PUFAs) to reduce the risk, growth and progression of colon cancer. Several of these studies have also emphasized the importance of a reduced dietary ω-6 PUFA/ω-3 PUFA ratio to diminish the risk. The beneficial anti-tumor effects of ω-3 PUFAs have been also largely demonstrated in colon cancer cells treated in vitro with these fatty acids. The synergic action of combinations of ω-3 PUFAs and other anti-neoplastic agents have been also demonstrated both in vivo and in vitro. On the contrary, just a few human interventional trials have been conducted so far, but there is complete agreement among them and with the experimental studies on the anti-tumor efficacy of increased dietary intakes of ω-3 PUFAs

    Reduction of Oxidative/Nitrosative Stress in Brain and its Involvement in the Neuroprotective Effect of n-3 PUFA in Alzheimer's Disease.

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    Plenty of evidence has shown that an enhanced oxidative or nitrosative stress may play a central role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). The suppressive effect of n-3 polyunsaturated fatty acids (n-3 PUFA) against oxidative/nitrosative stressinduced injury in nervous tissues has recently received increasing interest. A number of human experimental studies have concurred to demonstrate that they may exert a substantial preventive role, especially in the very early phase of mild cognitive impairment (MCI) preceding AD. It has been suggested that they may exert an indirect antioxidant/anti-nitrosative role by modulating the expression/ activity of several proteins involved in the modulation of oxidative stress in nervous tissues. In particular, recent data have supported the hypothesis that in the early phase of MCI the light to moderate oxidative stress triggered by not cytotoxic doses of n-3 PUFA can positively regulate the transcriptional activity of nuclear factor erythroid 2-related factor 2 (Nrf2). This may result in the induced expression of heme oxygenase-1 (HO-1) and other antioxidant proteins transcriptionally regulated by Nrf2. Alternatively, the anti-inflammatory and antioxidant/anti-nitrosative effects of n-3 PUFA have been lately related to their ability to blunt microglia persistent activation occurring during chronic inflammation involved in the pathogenesis of neurodegenerative diseases. Evidences have been presented that n-3 PUFA may convert microglia from the macrophage M1 to an M2 phenotype showing lower production of neurotoxicoxidative factors and enhanced phagocytic activity toward Aβ peptide, or even to a further phenotype with neurotrophic/ protective properties

    Long-chain omega-3 fatty acids and cancer: any cause for concern?

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    PURPOSE OF REVIEW: Recently, concerns have been raised with regard to the recommended doses of marine long-chain omega-3 polyunsaturated fatty acids (LC-omega-3 PUFAs) especially in relation to cancer risk and treatment. There is urgent need to clarify this point. This review considers the most recent evidence related to the potential risk of developing cancer with high LC-omega-3 PUFA intakes, and possible research strategies to better elucidate this matter. RECENT FINDINGS: The latest published recommendations have still highlighted the usefulness of an increased dietary intake of LC-omega-3 PUFAs for the prevention of some cardiovascular diseases. However, LC-omega-3 PUFAs have been related to the potential development and progression of cancer, and considerable debate exists on this issue. SUMMARY: The use of biomarkers reflecting the intake of LC-omega-3 PUFAs as cancer risk markers is discussed, as well as the possibility that the reported beneficial/deleterious effects may be confined to specific subpopulations on the basis of genetic, metabolic, and nutritional characteristics. Recent advances on new strategies for a safer intake of LC-omega-3 PUFAs will be considered, as their dietary sources may be contaminated by toxic/carcinogenic compounds. Potentially future directions in this important research area are also discussed

    Nanomedicine-based formulations containing ω-3 polyunsaturated fatty acids: potential application in cardiovascular and neoplastic diseases.

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    Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are dietary factors involved in the prevention of cardiovascular, inflammatory, and neoplastic diseases. A multidisciplinary approach - based on recent findings in nutritional science, lipid biochemistry, biotechnology, and biology of inflammation and cancer - has been recently employed to develop ω-3 PUFA-containing nanoformulations with an aim to protect these fatty acids from degradation, increase their bioavailability and delivery to target tissues, and, thus, enhance their bioactivity. In some cases, these nanoformulations were designed to administer ω-3 PUFAs in combination with other nutraceuticals or conventional/innovative drugs. The aim of this strategy was to increase the activities of the compounds contained in the nanoformulation and to reduce the adverse effects often induced by drugs. We herein analyze the results of papers evaluating the potential use of ω-3 PUFA-containing nanomaterials in fighting cardiovascular diseases and cancer. Future directions in this field of research are also provide

    Preparation and Study of Solid Lipid Nanoparticles Based on Curcumin, Resveratrol and Capsaicin Containing Linolenic Acid

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    Linolenic acid (LNA) is the most highly consumed polyunsaturated fatty acid found in the human diet. It possesses anti-inflammatory effects and the ability to reverse skin-related disorders related to its deficiency. The purpose of this work was to encapsulate LNA in solid lipid nanoparticles (SLNs) based on curcumin, resveratrol and capsaicin for the treatment of atopic dermatitis. These compounds were first esterified with oleic acid to obtain two moonoleate and one oleate ester, then they were used for SLN matrix realization through the emulsification method. The intermediates of the esterification reaction were characterized by FT-IR and 1N-MR analysis. SLNs were characterized by dimensional analysis and encapsulation efficiency. Skin permeation studies, antioxidant and anti-inflammatory activities were evaluated. LNA was released over 24 h from nanoparticles, and resveratrol monooleate-filled SLNs exhibited a good antioxidant activity. The curcumin-based SLNs loaded or not with LNA did not induce significant cytotoxicity in NCTC 2544 and THP-1 cells. Moreover, these SLNs loaded with LNA inhibited the production of IL-6 in NCTC 2544 cells. Overall, our data demonstrate that the synthesized SLNs could represent an efficacious way to deliver LNA to skin cells and to preserve the anti-inflammatory properties of LNA for the topical adjuvant treatment of atopic dermatiti

    n-3 polyunsaturated fatty acids and the prevention of colorectal cancer: molecular mechanisms involved

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    Increasing evidence supports the hypothesis that nutrition habits play a critical role in the incidence and growth of colorectal cancer. Among dietary factors, fish-derived n-3 polyunsaturated fatty acids (PUFAs) have gained particular interest, since epidemiological studies have shown a reduced incidence of this cancer in populations consuming high levels of fish. Also a variety of experimental studies and different clinical trials substantiated the beneficial role of n-3 PUFAs. Such an anticancer activity has been related to the regulatory effects exhibited by n-3 PUFAs on cell proliferation and apoptosis. Antiangiogenic and antimetastatic effects have been also reported for these fatty acids. Finally, it has been suggested that they may act as adjuvant therapeutic agents sensitizing tumors, including colon cancer, to different anticancer drugs. Several molecular mechanisms have been hypothesized to explain their anti-neoplastic action and, in particular, the modulating effect on the expression of several proteins involved in the regulation of cell cycle and apoptosis, such as BCL-2, Bax, c-Myc seem to play a central role. Their inhibitory action has been also recently suggested for the molecular pathways driven by COX-2 and beta-catenin, known to play a major role in the development and progression of colon cancer. The aim of the present review is to analyze the anticancer effect of n-3 PUFAs towards colon cancer, and examine the molecular mechanisms involved

    Omega-3 PUFA Responders and Non-Responders and the Prevention of Lipid Dysmetabolism and Related Diseases.

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    The long-chain omega-3 polyunsaturated fatty acids (LC-omega-3 PUFAs) eicosapentaenoic acid and docosahexaenoic acid are the most popular dietary supplements recommended for the prevention/management of lipid dysmetabolisms and related diseases. However, remarkable inconsistencies exist among the outcomes of the human intervention studies in this field, which contrast with the impressive homogeneity of positive results of most of the preclinical studies. In the present review, we will firstly examine a series of factors-such as background diet composition, gut microbiota and genetic/epigenetic variants, which may lie beneath these inconsistencies. Moreover, we will discuss the recent advance in the knowledge of possible specific biomarkers (genetic-, epigenetic- and microbiota-related) that are being investigated with the goal to apply them in a personalized supplementation with omega-3 PUFAs. We will also consider the possibility of using already available parameters (Omega-3 index, Omega-6 PUFA/Omega-3 PUFA ratio) able to predict the individual responsiveness to these fatty acids and will discuss the optimal timing for their use. Finally, we will critically examine the results of those human studies that have already adopted the distinction of the subjects into omega-3 PUFA responders and non-responders and will discuss the advantage of using such an approach

    Dietary n-3 PUFA vascular targeting and the prevention of tumor growth and age-related macular degeneration.

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    The protective role of dietary n-3 polyunsaturated fatty acids (PUFAs) against cardiovascular diseases has been partly related to their ability to modulate the risk condition known as "endothelial dysfunction", by reverting the endothelial alterations associated to it (reduced vascular reactivity, the proinflammatory state, and the prothrombotic properties). Moreover, vasculature represents the target for inhibition of pathologic neo-angiogenesis by n-3 PUFAs. This effect is believed to contribute to the beneficial action of these fatty acids against disorders which recognize neovascularization as a crucial pathogenetic step for their development, such as cancer and age-related macular degeneration (AMD). Many epidemiological studies have been conducted to evaluate the association between the intake of these fatty acids and the risk of developing cancer or AMD, even though contrasting and not definitive results have been obtained. Conversely, plenty of preclinical and in vitro experimental studies have provided evidence for the anti-angiogenic effects of n-3 PUFAs, mainly studying neo-angiogenesis in general (using normal endothelial cells in vitro) or as a step of cancer growth. The main aim of this review is to critically review the current evidence for the inhibition of the neo-angiogenic process exerted by n-3 PUFAs in cancer and AMD, and to identify possible molecular mechanisms that might contribute to their beneficial effects

    Carotenoids as Modulators of Intracellular Signaling Pathways

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    Carotenoids have been proposed to exert beneficial effects in several chronic diseases, including cancer and cardiovascular diseases. Many of the biological actions of carotenoids have been attributed to their antioxidant properties, through the antioxidant capacity of the carotenoid molecule per se or through their possible influences on intracellular redox status. However, the exact mechanism by which carotenoids exert their beneficial effects are still under debate. Increasing evidence show that carotenoids, and their metabolites, may modulate molecular pathways involved in cell proliferation, acting at Akt, tyrosine kinases, mitogen activated protein kinase (MAP kinase) and growth factor signalling cascades. Moreover, there is now strong evidence for an involvement of carotenoids in the regulation of apoptosis through modulatory effects on the activation of caspase cascade and on the expression of Bcl-2 family proteins and transcription factors. Inhibitory or stimulatory actions at these pathways are likely to affect cellular functions by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of carotenoids, either as redox agents or modulators of cell signalling and the influence of their metabolism on these properties is key to the evaluation of these biomolecules as anticancer and cardioprotective agents
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