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Sample records for bioactive lipid mediators

  1. Bioactive Lipids in Dairy Fat

    DEFF Research Database (Denmark)

    Hellgren, Lars; Nordby, Pernille

    2017-01-01

    Milk fat is the most important energy source for the newborn infant beside its important role as energy source, milk fat also contain a range of bioactive lipids, that potentially can modulate the immune response and metabolic regulation in the child. In this chapter we review the literature on b...... on bioactive dairy fatty acids: conjugated linoleic acid, branched chained and odd chained fatty acids, as well as bioactive complex lipids such as sphingomyelin and gangliosides....

  2. Bioactive lipids in kidney physiology and pathophysiology

    Directory of Open Access Journals (Sweden)

    Daria Sałata

    2014-01-01

    Full Text Available Lipids not only have structural functions, but also play an important role as signaling and regulatory molecules and participate in many cellular processes such as proliferation, differentiation, migration, and apoptosis. Bioactive lipids act both as extracellular mediators, which are associated with receptors on the surface of cells, and intracellular mediators triggering different signal pathways. They are present and active in physiological conditions, and are also involved in the pathogenesis of inflammation, asthma, cancer, diabetes, and hypertension. Bioactive lipids such as derivatives of arachidonic acid and sphingolipids have an important role in renal development, physiology and in many renal diseases. Some of them are potential indicators of kidney damage degree and/or function of the transplanted kidneys.

  3. Bioactive Lipids and Chronic Inflammation: Managing the Fire Within

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    Valerio Chiurchiù

    2018-01-01

    Full Text Available Inflammation is an immune response that works as a contained fire that is pre-emptively sparked as a defensive process during infections or upon any kind of tissue insult, and that is spontaneously extinguished after elimination or termination of the damage. However, persistent and uncontrolled immune reactions act as a wildfire that promote chronic inflammation, unresolved tissue damage and, eventually, chronic diseases. A wide network of soluble mediators, among which endogenous bioactive lipids, governs all immune processes. They are secreted by basically all cells involved in inflammatory processes and constitute the crucial infrastructure that triggers, coordinates and confines inflammatory mechanisms. However, these molecules are also deeply involved in the detrimental transition from acute to chronic inflammation, be it for persistent or excessive action of pro-inflammatory lipids or for the impairment of the functions carried out by resolving ones. As a matter of fact, bioactive lipids have been linked, to date, to several chronic diseases, including rheumatoid arthritis, atherosclerosis, diabetes, cancer, inflammatory bowel disease, systemic lupus erythematosus, and multiple sclerosis. This review summarizes current knowledge on the involvement of the main classes of endogenous bioactive lipids—namely classical eicosanoids, pro-resolving lipid mediators, lysoglycerophospholipids/sphingolipids, and endocannabinoids—in the cellular and molecular mechanisms that lead to the pathogenesis of chronic disorders.

  4. Pathophysiology of mitochondrial lipid oxidation: Role of 4-hydroxynonenal (4-HNE) and other bioactive lipids in mitochondria.

    Science.gov (United States)

    Xiao, Mengqing; Zhong, Huiqin; Xia, Lin; Tao, Yongzhen; Yin, Huiyong

    2017-10-01

    Mitochondrial lipids are essential for maintaining the integrity of mitochondrial membranes and the proper functions of mitochondria. As the "powerhouse" of a cell, mitochondria are also the major cellular source of reactive oxygen species (ROS). Oxidative stress occurs when the antioxidant system is overwhelmed by overproduction of ROS. Polyunsaturated fatty acids in mitochondrial membranes are primary targets for ROS attack, which may lead to lipid peroxidation (LPO) and generation of reactive lipids, such as 4-hydroxynonenal. When mitochondrial lipids are oxidized, the integrity and function of mitochondria may be compromised and this may eventually lead to mitochondrial dysfunction, which has been associated with many human diseases including cancer, cardiovascular diseases, diabetes, and neurodegenerative diseases. How mitochondrial lipids are oxidized and the underlying molecular mechanisms and pathophysiological consequences associated with mitochondrial LPO remain poorly defined. Oxidation of the mitochondria-specific phospholipid cardiolipin and generation of bioactive lipids through mitochondrial LPO has been increasingly recognized as an important event orchestrating apoptosis, metabolic reprogramming of energy production, mitophagy, and immune responses. In this review, we focus on the current understanding of how mitochondrial LPO and generation of bioactive lipid mediators in mitochondria are involved in the modulation of mitochondrial functions in the context of relevant human diseases associated with oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Bioactive lipids as radioprotectors and potentiators of radiotherapy

    International Nuclear Information System (INIS)

    Das, Undurti N.

    2016-01-01

    Selective elimination of tumor cells with little or no effects on normal cells is desirable for the treatment of cancer. Radiotherapy, a well accepted form of cancer therapy, is associated with significant side effects that need to be eliminated or dampened. Our studies revealed that radiation can produce significant changes in the metabolism of essential fatty acids that could be related to its actions and side effects. It was noted that UVB exposed skin produced PGE2, PGF2a and PGE3 that accompany the erythema in the first 24-48 h, associated with increased COX-2 expression at 24 h. Leukocyte chemoattractants 11-, 12- and 8-monohydroxy-eicosatetraenoic acid (HETE) are elevated from 4 to 72 h, in association with peak dermal neutrophil influx at 24 h, and increased dermal CD3"+ lymphocytes and 12- and 15-LOX expression from 24 to 72 h. On the other hand, anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72 h. Thus, skin lesions are characterized by overlapping sequential profiles of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution. The enhanced expression of 15-HETE at 72 h is interesting since it forms the precursor to antiinflammatory bioactive lipids. We and others also showed that the anti-cancer action of radiation and chemotherapeutic drugs can be augmented by certain polyunsaturated fatty acids with little or no action on normal cells. Even tumor cell drug resistance could be reversed by these bioactive lipids. Our recent studies revealed that these bioactive lipids also prevent genetic damage induced by radiation and other drugs. These studies imply that employing certain bioactive lipids may be exploited as radiation protective molecules and as enhancers of the anti-cancer action of radiation in the therapy of cancer. (author)

  6. Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?

    Science.gov (United States)

    Li, Shengxian; Chu, Qianqian; Ma, Jing; Sun, Yun; Tao, Tao; Huang, Rong; Liao, Yu; Yue, Jiang; Zheng, Jun; Wang, Lihua; Xue, Xinli; Zhu, Mingjiang; Kang, Xiaonan; Yin, Huiyong; Liu, Wei

    2017-03-01

    Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction. This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. Thirty-two newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was used to validate results of the human studies. Serum lipid profiles, including phospholipids, free fatty acids (FFAs), and bioactive lipids, were analyzed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS. Elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid were found in obese patients with PCOS vs lean controls. Obese patients with PCOS had decreased PUFA levels and increased levels of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean patients with PCOS vs their respective controls. Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in patients with PCOS, particularly on the bioactive lipid metabolites derived from PUFAs. These clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity. Copyright © 2017 by the Endocrine Society

  7. Bioactive Structure of Membrane Lipids and Natural Products Elucidated by a Chemistry-Based Approach.

    Science.gov (United States)

    Murata, Michio; Sugiyama, Shigeru; Matsuoka, Shigeru; Matsumori, Nobuaki

    2015-08-01

    Determining the bioactive structure of membrane lipids is a new concept, which aims to examine the functions of lipids with respect to their three-dimensional structures. As lipids are dynamic by nature, their "structure" does not refer solely to a static picture but also to the local and global motions of the lipid molecules. We consider that interactions with lipids, which are completely defined by their structures, are controlled by the chemical, functional, and conformational matching between lipids and between lipid and protein. In this review, we describe recent advances in understanding the bioactive structures of membrane lipids bound to proteins and related molecules, including some of our recent results. By examining recent works on lipid-raft-related molecules, lipid-protein interactions, and membrane-active natural products, we discuss current perspectives on membrane structural biology. © 2015 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. The role of ATP-binding cassette transporters in neuro-inflammation: relevance for bioactive lipids

    Directory of Open Access Journals (Sweden)

    Gijs eKooij

    2012-04-01

    Full Text Available ATP-binding cassette (ABC transporters are highly expressed by brain endothelial cells that form the blood-brain barrier (BBB. These efflux pumps play an important role in maintaining brain homeostasis as they actively hinder the entry of unwanted blood-derived compounds into the central nervous system (CNS. Consequently, their high activity at the BBB has been a major hurdle for the treatment of several brain diseases, as they prevent numerous drugs to reach their site of action within the brain. Importantly, recent data indicate that endogenous substrates for ABC transporters may include inflammatory mediators, such as prostaglandins, leukotrienes, cytokines, chemokines and bioactive lipids, suggesting a potential role for ABC transporters in immunological responses, and more specifically in inflammatory brain disorders, such as multiple sclerosis (MS. In this review, we will give a comprehensive overview of recent findings that illustrate this novel role for ABC transporters in neuro-inflammatory processes. Moreover, we will provide first insights into underlying mechanisms and focus on the importance for bioactive lipids, in particular platelet-activating factor (PAF, herein. A thorough understanding of these events may form the basis for the development for selective treatment modalities to dampen the neuro-inflammatory attack in MS and thereby reducing tissue damage.

  9. Effects of a new bioactive lipid-based drug carrier on cultured hepatic stellate cells and liver fibrosis in bile duct-ligated rats

    NARCIS (Netherlands)

    Adrian, Joanna E.; Poelstra, Klaas; Scherphof, Gerrit L.; Meijer, Dirk K. F.; van Loenen - Weemaes, Anne-miek; Reker-Smit, Catharina; Morselt, Henriette W. M.; Zwiers, Peter; Kamps, Jan A. A. M.

    In the fibrotic liver, hepatic stellate cells ( HSC) produce large amounts of collagen and secrete variety of mediators that promote development of fibrosis in this organ. Therefore, these cells are considered an attractive target for antifibrotic therapies. We incorporated the bioactive lipid

  10. The Mediator Complex and Lipid Metabolism.

    Science.gov (United States)

    Zhang, Yi; Xiaoli; Zhao, Xiaoping; Yang, Fajun

    2013-03-01

    The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.

  11. Levels of bioactive lipids in cooking oils: olive oil is the richest source of oleoyl serine.

    Science.gov (United States)

    Bradshaw, Heather B; Leishman, Emma

    2016-05-01

    Rates of osteoporosis are significantly lower in regions of the world where olive oil consumption is a dietary cornerstone. Olive oil may represent a source of oleoyl serine (OS), which showed efficacy in animal models of osteoporosis. Here, we tested the hypothesis that OS as well as structurally analogous N-acyl amide and 2-acyl glycerol lipids are present in the following cooking oils: olive, walnut, canola, high heat canola, peanut, safflower, sesame, toasted sesame, grape seed, and smart balance omega. Methanolic lipid extracts from each of the cooking oils were partially purified on C-18 solid-phase extraction columns. Extracts were analyzed with high-performance liquid chromatography-tandem mass spectrometry, and 33 lipids were measured in each sample, including OS and bioactive analogs. Of the oils screened here, walnut oil had the highest number of lipids detected (22/33). Olive oil had the second highest number of lipids detected (20/33), whereas grape-seed and high-heat canola oil were tied for lowest number of detected lipids (6/33). OS was detected in 8 of the 10 oils tested and the levels were highest in olive oil, suggesting that there is something about the olive plant that enriches this lipid. Cooking oils contain varying levels of bioactive lipids from the N-acyl amide and 2-acyl glycerol families. Olive oil is a dietary source of OS, which may contribute to lowered prevalence of osteoporosis in countries with high consumption of this oil.

  12. Influence of encapsulated functional lipids on crystal structure and chemical stability in solid lipid nanoparticles: Towards bioactive-based design of delivery systems.

    Science.gov (United States)

    Salminen, Hanna; Gömmel, Christina; Leuenberger, Bruno H; Weiss, Jochen

    2016-01-01

    We investigated the influence of physicochemical properties of encapsulated functional lipids--vitamin A, β-carotene and ω-3 fish oil--on the structural arrangement of solid lipid nanoparticles (SLN). The relationship between the crystal structure and chemical stability of the incorporated bioactive lipids was evaluated with different emulsifier compositions of a saponin-rich, food-grade Quillaja extract alone or combined with high-melting or low-melting lecithins. The major factors influencing the structural arrangement and chemical stability of functional lipids in solid lipid dispersions were their solubility in the aqueous phase and their crystallization temperature in relation to that of the carrier lipid. The results showed that the stabilization of the α-subcell crystals in the lattice of the carrier lipid is a key parameter for forming stable solid lipid dispersions. This study contributes to a better understanding of SLN as a function of the bioactive lipid. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins

    NARCIS (Netherlands)

    Neumann, S.

    2008-01-01

    Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins In this thesis, I studied the intra- and intercellular transport of lipidic molecules, in particular glycosphingolipids and lipid-modified proteins. The first part focuses on the intracellular transport of

  14. Increased bioactive lipids content in human subcutaneous and epicardial fat tissue correlates with insulin resistance.

    Science.gov (United States)

    Błachnio-Zabielska, Agnieszka U; Baranowski, Marcin; Hirnle, Tomasz; Zabielski, Piotr; Lewczuk, Anna; Dmitruk, Iwona; Górski, Jan

    2012-12-01

    Obesity is a risk factor for metabolic diseases. Intramuscular lipid accumulation of ceramides, diacylglycerols, and long chain acyl-CoA is responsible for the induction of insulin resistance. These lipids are probably implicated in obesity-associated insulin resistance not only in skeletal muscle but also in fat tissue. Only few data are available about ceramide content in human subcutaneous adipose tissue. However, there are no data on DAG and LCACoA content in adipose tissue. The aim of our study was to measure the lipids content in human SAT and epicardial adipose tissue we sought to determine the bioactive lipids content by LC/MS/MS in fat tissue from lean non-diabetic, obese non-diabetic, and obese diabetic subjects and test whether the lipids correlate with HOMA-IR. We found, that total content of measured lipids was markedly higher in OND and OD subjects in both types of fat tissue (for all p lipids content is greater in subcutaneous and epicardial fat tissue and the particular lipids content positively correlates with HOMA-IR.

  15. Is There a Role for Bioactive Lipids in the Pathobiology of Diabetes Mellitus?

    Directory of Open Access Journals (Sweden)

    Undurti N. Das

    2017-08-01

    Full Text Available Inflammation, decreased levels of circulating endothelial nitric oxide (eNO and brain-derived neurotrophic factor (BDNF, altered activity of hypothalamic neurotransmitters (including serotonin and vagal tone and gut hormones, increased concentrations of free radicals, and imbalance in the levels of bioactive lipids and their pro- and anti-inflammatory metabolites have been suggested to play a role in diabetes mellitus (DM. Type 1 diabetes mellitus (type 1 DM is due to autoimmune destruction of pancreatic β cells because of enhanced production of IL-6 and tumor necrosis factor-α (TNF-α and other pro-inflammatory cytokines released by immunocytes infiltrating the pancreas in response to unknown exogenous and endogenous toxin(s. On the other hand, type 2 DM is due to increased peripheral insulin resistance secondary to enhanced production of IL-6 and TNF-α in response to high-fat and/or calorie-rich diet (rich in saturated and trans fats. Type 2 DM is also associated with significant alterations in the production and action of hypothalamic neurotransmitters, eNO, BDNF, free radicals, gut hormones, and vagus nerve activity. Thus, type 1 DM is because of excess production of pro-inflammatory cytokines close to β cells, whereas type 2 DM is due to excess of pro-inflammatory cytokines in the systemic circulation. Hence, methods designed to suppress excess production of pro-inflammatory cytokines may form a new approach to prevent both type 1 and type 2 DM. Roux-en-Y gastric bypass and similar surgeries ameliorate type 2 DM, partly by restoring to normal: gut hormones, hypothalamic neurotransmitters, eNO, vagal activity, gut microbiota, bioactive lipids, BDNF production in the gut and hypothalamus, concentrations of cytokines and free radicals that results in resetting glucose-stimulated insulin production by pancreatic β cells. Our recent studies suggested that bioactive lipids, such as arachidonic acid, eicosapentaneoic acid, and docosahexaenoic

  16. Novel bio-active lipid nanocarriers for the stabilization and sustained release of sitosterol

    International Nuclear Information System (INIS)

    Lacatusu, I; Badea, N; Stan, R; Meghea, A

    2012-01-01

    In this work, new stable and efficiently bio-active lipid nanocarriers (NLCs) with antioxidant properties have been developed for the transport of active ingredients in food. The novel NLCs loaded with β-sitosterol/β-sitosterol and green tea extract (GTE) and prepared by a combination of natural oils (grape seed oil, fish oil and squalene) and biological lipids with food grade surfactants, were physico-chemically examined by DLS, TEM, electrokinetic potential, DSC and HPLC and found to have main diameters less than 200 nm, a spherical morphology, excellent physical stability, an imperfect crystalline lattice and high entrapment efficiency. The novel loaded-NLCs have demonstrated the potential to develop a high blocking action of chain reactions, trapping up to 92% of the free-oxygen radicals, as compared to the native β-sitosterol (AA%=36.5). Another advantage of this study is associated with the quality of bio-active NLCs based on grape seed oil and squalene to manifest a better sitosterol—sustained release behaviour as compared to their related nanoemulsions. By coupling both in vitro results, i.e. the enhanced antioxidant activity and superior release properties, this study emphasizes the sustainability of novel bio-active nanocarriers to gain specific bio-food features for development of functional foods with a high applicability spectrum. (paper)

  17. Bioactivities of Milk Polar Lipids in Influencing Intestinal Barrier Integrity, Systemic Inflammation, and Lipid Metabolism

    OpenAIRE

    Zhou, Albert Lihong

    2013-01-01

    The purpose of lactation is for nutrient provision and also importantly for protection from various environmental stressors. Milk polar lipids reduce cholesterol, protect against bacterial infection, reduce inflammation and help maintain gut integrity. Dynamic interactions within dietary fat, lipid metabolism, gut permeability and inflammatory cytokines remain unclear in the context of obesity and systemic inflammation. A rat model and three mouse models were developed to test the hypotheses ...

  18. Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

    Science.gov (United States)

    Markworth, James F.; Vella, Luke; Lingard, Benjamin S.; Tull, Dedreia L.; Rupasinghe, Thusitha W.; Sinclair, Andrew J.; Maddipati, Krishna Rao

    2013-01-01

    Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a

  19. The Role of Bioactive Lipids in Stem Cell Mobilization and Homing: Novel Therapeutics for Myocardial Ischemia

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    Yuri M. Klyachkin

    2014-01-01

    Full Text Available Despite significant advances in medical therapy and interventional strategies, the prognosis of millions of patients with acute myocardial infarction (AMI and ischemic heart disease (IHD remains poor. Currently, short of heart transplantation with all of its inherit limitations, there are no available treatment strategies that replace the infarcted myocardium. It is now well established that cardiomyocytes undergo continuous renewal, with contribution from bone marrow (BM-derived stem/progenitor cells (SPCs. This phenomenon is upregulated during AMI by initiating multiple innate reparatory mechanisms through which BMSPCs are mobilized towards the ischemic myocardium and contribute to myocardial regeneration. While a role for the SDF-1/CXCR4 axis in retention of BMSPCs in bone marrow is undisputed, its exclusive role in their mobilization and homing to a highly proteolytic microenvironment, such as the ischemic/infarcted myocardium, is currently being challenged. Recent evidence suggests a pivotal role for bioactive lipids in the mobilization of BMSPCs at the early stages following AMI and their homing towards ischemic myocardium. This review highlights the recent advances in our understanding of the mechanisms of stem cell mobilization, provides newer evidence implicating bioactive lipids in BMSPC mobilization and differentiation, and discusses their potential as therapeutic agents in the treatment of IHD.

  20. Host Lipid Mediators in Leprosy: The Hypothesized Contributions to Pathogenesis

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    Carlos A. M. Silva

    2018-02-01

    Full Text Available The spectrum of clinical forms observed in leprosy and its pathogenesis are dictated by the host’s immune response against Mycobacterium leprae, the etiological agent of leprosy. Previous results, based on metabolomics studies, demonstrated a strong relationship between clinical manifestations of leprosy and alterations in the metabolism of ω3 and ω6 polyunsaturated fatty acids (PUFAs, and the diverse set of lipid mediators derived from PUFAs. PUFA-derived lipid mediators provide multiple functions during acute inflammation, and some lipid mediators are able to induce both pro- and anti-inflammatory responses as determined by the cell surface receptors being expressed, as well as the cell type expressing the receptors. However, little is known about how these compounds influence cellular immune activities during chronic granulomatous infectious diseases, such as leprosy. Current evidence suggests that specialized pro-resolving lipid mediators (SPMs are involved in the down-modulation of the innate and adaptive immune response against M. leprae and that alteration in the homeostasis of pro-inflammatory lipid mediators versus SPMs is associated with dramatic shifts in the pathogenesis of leprosy. In this review, we discuss the possible consequences and present new hypotheses for the involvement of ω3 and ω6 PUFA metabolism in the pathogenesis of leprosy. A specific emphasis is placed on developing models of lipid mediator interactions with the innate and adaptive immune responses and the influence of these interactions on the outcome of leprosy.

  1. Bioactive compounds in lipid fractions of pumpkin (Cucurbita sp) seeds for use in food.

    Science.gov (United States)

    Veronezi, Carolina Médici; Jorge, Neuza

    2012-06-01

    Seeds are considered to be agro-industrial residues, which can be used as source of macronutrients and/or raw material for extraction of vegetable oils, since they present great quantities of bioactive compounds. This study aimed to characterize the lipid fractions and the seeds of pumpkin (Cucurbita sp) varieties Nova Caravela, Mini Paulista, Menina Brasileira, and Moranga de Mesa aiming at using them in food. The chemical composition of the seeds was performed according to the official methods of American Oil Chemists' Society and Association of Official Analytical Chemists. Total carotenoids and phenolic compounds were determined by spectrophotometry, while the levels of tocopherols were analyzed by high efficiency liquid chromatography. It was noted that the seeds contain high amounts of macronutrients that are essential for the functioning of the human organism. As to total carotenoids, Mini Paulista and Menina Brasileira pumpkin varieties presented significant amounts, 26.80 and 26.03 μg/g, respectively. Mini Paulista and Nova Caravela pumpkin varieties showed high amounts of total phenolic compounds in the lipid fractions and in the seeds. It was also found that γ-tocopherol is the isomer that stood out in the lipid fractions and in the seeds, mainly in Menina Brasileira. Finally, the consumption of these seeds and use of lipid fractions provide the supply of large quantities of compounds that are beneficial for health and that may be potentially used in food, besides representing an alternative to better use of agro-industrial residues. Bioactive compounds, besides presenting basic nutritional functions, provide metabolic and physiological health benefits when consumed as part of the usual diet. Therefore, there is a growing interest in vegetable oils of special composition, such as the ones extracted from fruit seeds. The seeds of Cucurbita sp are shown to be promising sources of oils, and especially the Cucurbita moschata and maxima species have not yet

  2. Essential fatty acids and lipid mediators. Endocannabinoids

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    G. Caramia

    2012-03-01

    Full Text Available In 1929 Burr and Burr discovered the essential fatty acids omega-6 and omega-3. Since then, researchers have shown a growing interest in polyunsaturated fatty acids (PUFA as precursors of “lipid mediator” molecules, often with opposing effects, prostaglandins, prostacyclins, thromboxanes, leukotrienes, lipossines, resolvines, protectines, maresins that regulate immunity, platelet aggregation, inflammation, etc. They showed that the balance between omega-3 and omega-6 acids has a profound influence on all the body’s inflammatory responses and a raised level of PUFA omega-3 in tissue correlate with a reduced incidence of degenerative cardiovascular disease, some mental illnesses such as depression, and neuro-degenerative diseases such as Alzheimer’s. The CYP-catalyzed epoxidation and hydroxylation of arachidonic acid (AA were established recently as the so-called third branch of AGE cascade. Cytochrome P450 (CYP epoxygenases convert AA to four epoxyeicosatrienoic acid (EET regioisomers, that produce vascular relaxation anti-inflammatory effects on blood vessels and in the kidney, promote angiogenesis, and protect ischemic myocardium and brain. Eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA are accessible to CYP enzymes in the same way as AA. Metabolites derived from EPA include epoxyeicosatetraenoic acids (EETR and hydroxyeicosapentaenoic acids (19- and 20-HEPE, whereas DHA include epoxydocosapentaenoic acids (EDPs hydroxydocosahexaenoic acids (21- and 22-HDoHE. For many of the CYP isoforms, the n-3 PUFAs are the preferred substrates and the available data suggest that some of the vasculo- and cardioprotective effects attributed to dietary n-3 PUFAs may be mediated by CYP-dependent metabolites of EPA and DHA. From AA derives also endocannabinoids like anandamide (N-arachidonoylethanolamine and 2-arachidonoylglycerol, capable of mimicking the pharmacological actions of the active principle of Cannabis sativa preparations such as

  3. Lipidomic Approaches towards Deciphering Glycolipids from Microalgae as a Reservoir of Bioactive Lipids

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    Elisabete da Costa

    2016-05-01

    Full Text Available In recent years, noteworthy research has been performed around lipids from microalgae. Among lipids, glycolipids (GLs are quite abundant in microalgae and are considered an important source of fatty acids (FAs. GLs are rich in 16- and 18-carbon saturated and unsaturated fatty acids and often contain polyunsaturated fatty acids (PUFAs like n-3 α-linolenic (ALA 18:3, eicosapentaenoic (EPA, 20:5 and docosahexaenoic (DHA, 22:6. GLs comprise three major classes: monogalactosyldiacyl glycerolipids (MGDGs, digalactosyl diacylglycerolipids (DGDGs and sulfoquinovosyl diacylglycerolipids (SQDGs, whose composition in FA directly depends on the growth conditions. Some of these lipids are high value-added compounds with antitumoral, antimicrobial and anti-inflammatory activities and also with important nutritional significance. To fully explore GLs’ bioactive properties it is necessary to fully characterize their structure and to understand the relation between the structure and their biological properties, which can be addressed using modern mass spectrometry (MS-based lipidomic approaches. This review will focus on the up-to-date FA composition of GLs identified by MS-based lipidomics and their potential as phytochemicals.

  4. Azadirachta indica Mediated Bioactive Lyocell Yarn: Chemical and Colour Characterization

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    B. H. Patel

    2014-01-01

    Full Text Available The study deals with preparing aesthetic textiles using methanolic extract of Azadirachta indica leaves. The extract with metallic and natural mordents was utilized to create various shades on lyocell yarn using exhaust technique of dyeing. Aesthetic values of dyed yarns were analyzed in terms of colourimetric parameters, that is, CIE L*  a*  b* and colour fastness. The attachment of Azadirachta indica compounds has been confirmed by using infrared spectroscopy (IR analysis. The dyed samples exhibit moderate to good fastness properties. The study showed that lyocell yarn treated at 15% (owf methanolic extract of Azadirachta indica leaves can be utilized as effective bioactive textiles. Azadirachta indica is an alternative to synthetic antimicrobial agents. This bioactive yarn can be used in fashion as well as in medicinal industry.

  5. Semiconductor particle mediated photoelectron transfers in bilayer lipid membranes

    International Nuclear Information System (INIS)

    Fendler, J.H.; Baral, S.

    1989-01-01

    This paper discusses semiconductor particles in situ generated on the cis surface of glyceryl monooleate (GMO) bilayer lipid membranes (BLMs), that have been used to mediate photoelectric effects. The presence of semiconductors on the BLM surface is addressed. The observed photoelectric effects are rationalized and presented

  6. Molecular simulations of lipid-mediated protein-protein interactions

    NARCIS (Netherlands)

    de Meyer, F.J.M.; Venturoli, M.; Smit, B.

    2008-01-01

    Recent experimental results revealed that lipid-mediated interactions due to hydrophobic forces may be important in determining the protein topology after insertion in the membrane, in regulating the protein activity, in protein aggregation and in signal transduction. To gain insight into the

  7. The Mediator Complex and Lipid Metabolism

    OpenAIRE

    Zhang, Yi; Xiaoli,; Zhao, Xiaoping; Yang, Fajun

    2013-01-01

    The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understan...

  8. Bioactive Phytochemicals: Bioactivity, Sources, Preparations, and/or Modifications via Silver Tetrafluoroborate Mediation

    Directory of Open Access Journals (Sweden)

    Matthew C. Achilonu

    2015-01-01

    Full Text Available This review provides an overview of the biological activities, natural occurrences, and the silver tetrafluoroborate- (AgBF4- mediated synthesis of proanthocyanidins, glycosides, N-heterocyclic alkaloid analogues (of pyrrole, morphine, quinoline, isoquinoline, and indole, furan analogues, and halocompounds. AgBF4 has been reviewed as an effective reaction promoter, used extensively in the synthesis of relevant biologically active compounds via carbon-carbon and carbon-heteroatom bonds formation. The literatures from 1979 to April 2014 were reviewed.

  9. Atomistic study of lipid membranes containing chloroform: looking for a lipid-mediated mechanism of anesthesia.

    Directory of Open Access Journals (Sweden)

    Ramon Reigada

    Full Text Available The molecular mechanism of general anesthesia is still a controversial issue. Direct effect by linking of anesthetics to proteins and indirect action on the lipid membrane properties are the two hypotheses in conflict. Atomistic simulations of different lipid membranes subjected to the effect of small volatile organohalogen compounds are used to explore plausible lipid-mediated mechanisms. Simulations of homogeneous membranes reveal that electrostatic potential and lateral pressure transversal profiles are affected differently by chloroform (anesthetic and carbon tetrachloride (non-anesthetic. Simulations of structured membranes that combine ordered and disordered regions show that chloroform molecules accumulate preferentially in highly disordered lipid domains, suggesting that the combination of both lateral and transversal partitioning of chloroform in the cell membrane could be responsible of its anesthetic action.

  10. Effects of atopic dermatitis and gender on sebum lipid mediator and fatty acid profiles

    Science.gov (United States)

    Lipid mediator metabolism in skin is altered in some diseases. If mediators in skin secretions are influenced by skin health, they may provide useful clinical matrices with low subject burden. While lipid mediators in sweat can be altered by disease, the influences of skin diseases on sebum lipid me...

  11. Bioactive Extract from Moringa oleifera Inhibits the Pro-inflammatory Mediators in Lipopolysaccharide Stimulated Macrophages

    Science.gov (United States)

    Fard, Masoumeh Tangestani; Arulselvan, Palanisamy; Karthivashan, Govindarajan; Adam, Siti Khadijah; Fakurazi, Sharida

    2015-01-01

    Introduction: Inflammation is a well-known physiological response to protect the body against infection and restore tissue injury. Nevertheless, the chronic inflammation can trigger various inflammatory associated diseases/disorder. Moringa oleifera is a widely grown plant in most tropical countries and it has been recognized traditionally for several medicinal benefits. Objectives: The objective of this study was to investigate the anti-inflammatory properties of M. oleifera extract on lipopolysaccharide (LPS) - stimulated macrophages. Materials and Methods: The anti-inflammatory effect of M. oleifera hydroethanolic bioactive leaves extracts was evaluated by assessing the inhibition of nitric oxide (NO) production during Griess reaction and the expression of pro-inflammatory mediators in macrophages. Results: Interestingly, we found that M. oleifera hydroethanolic bioactive leaves extract significantly inhibited the secretion of NO production and other inflammatory markers such as prostaglandin E2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β. Meanwhile, the bioactive extract has induced the production of IL-10 in a dose-dependent manner. In addition, M. oleifera hydroethanolic bioactive leaves extract effectively suppressed the protein expression of inflammatory markers inducible NO synthase, cyclooxygenase-2, and nuclear factor kappa-light-chain-enhancer of activated B-cells p65 in LPS-induced RAW264.7 macrophages in a dose-dependent manner. Conclusion: These findings support the traditional use of M. oleifera plant as an effective treatment for inflammation associated diseases/disorders. SUMMARY Hydroethanolic extracts of Moringa oleifera effectively inhibit the NO production in LPS induced inflammatory model.M. oleifera crude extracts successfully modulate the production of pro-inflammatory mediators in LPS stimulated macrophages.M. oleifera extracts suppressed the expression of inflammatory mediators in LPS stimulated macrophages. PMID:27013794

  12. Aspirin and lipid mediators in the cardiovascular system.

    Science.gov (United States)

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

    Aspirin is an unique compound because it bears two active moieties within one and the same molecule: a reactive acetyl group and the salicylate metabolite. Salicylate has some effects similar to aspirin, however only at higher concentrations, usually in the millimolar range, which are not obtained at conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological actions of aspirin in the cardiovascular system at these doses are largely if not entirely due to target structure acetylation. Several classes of lipid mediators become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with subsequent inhibition of thromboxane and, possibly, thrombin formation. By this action, aspirin also inhibits paracrine thromboxane functions on other lipid mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates eNOS with subsequent upregulation of NO formation and enhanced expression of the antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated. Many more acetylation targets have been identified in live cells by quantitative acid-cleavable activity-based protein profiling and might result in discovery of even more aspirin targets in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Lysophosphatidic acid as a lipid mediator with multiple biological actions.

    Science.gov (United States)

    Aikawa, Shizu; Hashimoto, Takafumi; Kano, Kuniyuki; Aoki, Junken

    2015-02-01

    Lysophosphatidic acid (LPA) is one of the simplest glycerophospholipids with one fatty acid chain and a phosphate group as a polar head. Although LPA had been viewed just as a metabolic intermediate in de novo lipid synthetic pathways, it has recently been paid much attention as a lipid mediator. LPA exerts many kinds of cellular processes, such as cell proliferation and smooth muscle contraction, through cognate G protein-coupled receptors. Because lipids are not coded by the genome directly, it is difficult to know their patho- and physiological roles. However, recent studies have identified several key factors mediating the biological roles of LPA, such as receptors and producing enzymes. In addition, studies of transgenic and gene knockout animals for these LPA-related genes, have revealed the biological significance of LPA. In this review we will summarize recent advances in the studies of LPA production and its roles in both physiological and pathological conditions. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  14. Lipid-mediated protein functionalization of electrospun polycaprolactone fibers

    Directory of Open Access Journals (Sweden)

    C. Cohn

    2016-05-01

    Full Text Available In this study, electrospun polycaprolactone (PCL fibers are plasma-treated and chemically conjugated with cholesteryl succinyl silane (CSS. In addition to Raman spectroscopy, an immobilization study of DiO as a fluorescent probe of lipid membranes provides evidence supporting the CSS coating of plasma-treated PCL fibers. Further, anti-CD20 antibodies are used as a model protein to evaluate the potential of lipid-mediated protein immobilization as a mechanism to functionalize the CSS-PCL fiber scaffolds. Upon anti-CD20 functionalization, the CSS-PCL fiber scaffolds capture Granta-22 cells 2.4 times more than the PCL control does, although the two fiber scaffolds immobilize a comparable amount of anti-CD20. Taken together, results from the present study demonstrate that the CSS coating and CSS-mediated antibody immobilization offers an appealing strategy to functionalize electrospun synthetic polymer fibers and confer cell-specific functions on the fiber scaffolds, which can be mechanically robust but often lack biological functions.

  15. Fatty Acids, Lipid Mediators, and T-Cell Function

    Science.gov (United States)

    de Jong, Anja J.; Kloppenburg, Margreet; Toes, René E. M.; Ioan-Facsinay, Andreea

    2014-01-01

    Research toward the mechanisms underlying obesity-linked complications has intensified during the last years. As a consequence, it has become clear that metabolism and immunity are intimately linked. Free fatty acids and other lipids acquired in excess by current feeding patterns have been proposed to mediate this link due to their immune modulatory capacity. The functional differences between saturated and unsaturated fatty acids, in combination with their dietary intake are believed to modulate the outcome of immune responses. Moreover, unsaturated fatty acids can be oxidized in a tightly regulated and specific manner to generate either potent pro-inflammatory or pro-resolving lipid mediators. These oxidative derivatives of fatty acids have received detailed attention during the last years, as they have proven to have strong immune modulatory capacity, even in pM ranges. Both fatty acids and oxidized fatty acids have been studied especially in relation to macrophage and T-cells functions. In this review, we propose to focus on the effect of fatty acids and their oxidative derivatives on T-cells, as it is an active area of research during the past 5 years. The effect of fatty acids and their derivatives on activation and proliferation of T-cells, as well as the delicate balance between stimulation and lipotoxicity will be discussed. Moreover, the receptors involved in the interaction between free fatty acids and their derivatives with T-cells will be summarized. Finally, the mechanisms involved in modulation of T-cells by fatty acids will be addressed, including cellular signaling and metabolism of T-cells. The in vitro results will be placed in context of in vivo studies both in humans and mice. In this review, we summarize the latest findings on the immune modulatory function of lipids on T-cells and will point out novel directions for future research. PMID:25352844

  16. Ionic-Liquid-Mediated Extraction and Separation Processes for Bioactive Compounds: Past, Present, and Future Trends.

    Science.gov (United States)

    Ventura, Sónia P M; E Silva, Francisca A; Quental, Maria V; Mondal, Dibyendu; Freire, Mara G; Coutinho, João A P

    2017-05-24

    Ionic liquids (ILs) have been proposed as promising media for the extraction and separation of bioactive compounds from the most diverse origins. This critical review offers a compilation on the main results achieved by the use of ionic-liquid-based processes in the extraction and separation/purification of a large range of bioactive compounds (including small organic extractable compounds from biomass, lipids, and other hydrophobic compounds, proteins, amino acids, nucleic acids, and pharmaceuticals). ILs have been studied as solvents, cosolvents, cosurfactants, electrolytes, and adjuvants, as well as used in the creation of IL-supported materials for separation purposes. The IL-based processes hitherto reported, such as IL-based solid-liquid extractions, IL-based liquid-liquid extractions, IL-modified materials, and IL-based crystallization approaches, are here reviewed and compared in terms of extraction and separation performance. The key accomplishments and future challenges to the field are discussed, with particular emphasis on the major lacunas found within the IL community dedicated to separation processes and by suggesting some steps to overcome the current limitations.

  17. Sulfite induces release of lipid mediators by alveolar macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Beck-Speier, I.; Dayal, N.; Maier, L. [GSF - National Research Center for Environment and Health, Neuherberg (Germany). Inst. for Inhalation Biology; Denzlinger, C. [Tuebingen Univ. (Germany). Dept. II, Medical Clinic; Haberl, C. [Tuebingen Univ. (Germany). Dept. III, Medical Clinic

    1998-03-01

    Air pollutants are supposed to modulate physiological responses of alveolar macrophages (AM). This study was addressed to the question whether at neutral pH sulfur(IV) species in comparison to sulfur(VI) species cause AM to release proinflammatory mediators and which pathways are involved in their generation. Supernatants obtained from canine AM treated with sulfite (0.1 mM to 2 mM) enhanced the respiratory burst of canine neutrophils, measured by lucigenin-dependent chemiluminescence, whereas supernatants derived from AM treated with sulfate (1 mM) did not. The neutrophil-stimulating activity released by sulfite-treated AM consisted of platelet-activating factor (PAF) and leukotriene B{sub 4} (LTB{sub 4}) as shown by desensitization of the platelet-activating factor (PAF) and leukotriene B{sub 4} (LTB{sub 4}) as shown by desensitization of the corresponding receptors. Inhibitors of phospholipase A{sub 2} substantially suppressed release of neutrophil-stimulating activity by sulfite-treated AM. Inhibition of 5-lipoxygenase in sulfite-treated AM also reduced neutrophil-stimulating activity, while inhibition of cyclooxygenase had no effect. In conclusion, sulfite induces AM to release lipid mediators via phospholipase A{sub 2}- and 5-lipoxygenase-dependent pathways. These mediators activate neutrophils via the receptors for PAF and LTB{sub 4}. (orig.)

  18. Bioactive Constituents from “Triguero” Asparagus Improve the Plasma Lipid Profile and Liver Antioxidant Status in Hypercholesterolemic Rats

    Science.gov (United States)

    Vázquez-Castilla, Sara; De la Puerta, Rocío; Giménez, María Dolores García; Fernández-Arche, María Angeles; Guillén-Bejarano, Rafael

    2013-01-01

    We have previously shown that the Andalusian-cultivated Asparagus officinalis L. “triguero” variety produces hypocholesterolemic and hepatoprotective effects on rats. This asparagus is a rich source of phytochemicals although we hypothesized there would be some of them more involved in these functional properties. Thus, we aimed to study the effects of asparagus (500 mg/kg body weight (bw)/day) and their partially purified fractions in flavonoids (50 mg/kg bw/day), saponins (5 mg/kg bw/day) and dietary fiber (500 mg/kg bw/day) on oxidative status and on lipid profile in rats fed a cholesterol-rich diet. After 5 weeks treatment, plasma lipid values, hepatic enzyme activities and liver malondialdehyde (MDA) concentrations were measured. With the exception of the saponin fraction (SF), the administration of lyophilized asparagus (LA), fiber fraction (FF), and flavonoid fraction (FVF) to hypercholesterolemic rats produced a significant hypolipidemic effect compare to a high-cholesterol diet (HCD). In addition, the LA and FVF groups exhibited a significant increase in enzyme activity from multiple hepatic antioxidant systems including: superoxide dismutase, catalase, and gluthatione reductase/peroxidase as well as a decrease in MDA concentrations compared to HCD group. These results demonstrate that “triguero” asparagus possesses bioactive constituents, especially dietary fiber and flavonoids, that improve the plasma lipid profile and prevent hepatic oxidative damage under conditions of hypercholesterolemia. PMID:24284391

  19. Bioactive constituents from "triguero" asparagus improve the plasma lipid profile and liver antioxidant status in hypercholesterolemic rats.

    Science.gov (United States)

    Vázquez-Castilla, Sara; De la Puerta, Rocío; Garcia Gimenez, María Dolores; Fernández-Arche, María Angeles; Guillén-Bejarano, Rafael

    2013-10-24

    We have previously shown that the Andalusian-cultivated Asparagus officinalis L. "triguero" variety produces hypocholesterolemic and hepatoprotective effects on rats. This asparagus is a rich source of phytochemicals although we hypothesized there would be some of them more involved in these functional properties. Thus, we aimed to study the effects of asparagus (500 mg/kg body weight (bw)/day) and their partially purified fractions in flavonoids (50 mg/kg bw/day), saponins (5 mg/kg bw/day) and dietary fiber (500 mg/kg bw/day) on oxidative status and on lipid profile in rats fed a cholesterol-rich diet. After 5 weeks treatment, plasma lipid values, hepatic enzyme activities and liver malondialdehyde (MDA) concentrations were measured. With the exception of the saponin fraction (SF), the administration of lyophilized asparagus (LA), fiber fraction (FF), and flavonoid fraction (FVF) to hypercholesterolemic rats produced a significant hypolipidemic effect compare to a high-cholesterol diet (HCD). In addition, the LA and FVF groups exhibited a significant increase in enzyme activity from multiple hepatic antioxidant systems including: superoxide dismutase, catalase, and gluthatione reductase/peroxidase as well as a decrease in MDA concentrations compared to HCD group. These results demonstrate that "triguero" asparagus possesses bioactive constituents, especially dietary fiber and flavonoids, that improve the plasma lipid profile and prevent hepatic oxidative damage under conditions of hypercholesterolemia.

  20. Bioactive Constituents from “Triguero” Asparagus Improve the Plasma Lipid Profile and Liver Antioxidant Status in Hypercholesterolemic Rats

    Directory of Open Access Journals (Sweden)

    Rafael Guillén-Bejarano

    2013-10-01

    Full Text Available We have previously shown that the Andalusian-cultivated Asparagus officinalis L. “triguero” variety produces hypocholesterolemic and hepatoprotective effects on rats. This asparagus is a rich source of phytochemicals although we hypothesized there would be some of them more involved in these functional properties. Thus, we aimed to study the effects of asparagus (500 mg/kg body weight (bw/day and their partially purified fractions in flavonoids (50 mg/kg bw/day, saponins (5 mg/kg bw/day and dietary fiber (500 mg/kg bw/day on oxidative status and on lipid profile in rats fed a cholesterol-rich diet. After 5 weeks treatment, plasma lipid values, hepatic enzyme activities and liver malondialdehyde (MDA concentrations were measured. With the exception of the saponin fraction (SF, the administration of lyophilized asparagus (LA, fiber fraction (FF, and flavonoid fraction (FVF to hypercholesterolemic rats produced a significant hypolipidemic effect compare to a high-cholesterol diet (HCD. In addition, the LA and FVF groups exhibited a significant increase in enzyme activity from multiple hepatic antioxidant systems including: superoxide dismutase, catalase, and gluthatione reductase/peroxidase as well as a decrease in MDA concentrations compared to HCD group. These results demonstrate that “triguero” asparagus possesses bioactive constituents, especially dietary fiber and flavonoids, that improve the plasma lipid profile and prevent hepatic oxidative damage under conditions of hypercholesterolemia.

  1. Experimental resin cements containing bioactive fillers reduce matrix metalloproteinase-mediated dentin collagen degradation.

    Science.gov (United States)

    Osorio, Raquel; Yamauti, Monica; Sauro, Salvatore; Watson, Thimoty F; Toledano, Manuel

    2012-09-01

    Collagen dentin matrix may represent a suitable scaffold to be remineralized in the presence of bioactive materials. The purpose of this study was to determine if experimental resin cements containing bioactive fillers may modulate matrix metalloproteinase-mediated collagen degradation of etched dentin. Human dentin beams demineralized using 10% phosphoric acid or 0.5 mol/L EDTA were infiltrated with the following experimental resins: (1) unfilled resin, (2) resin with Bioglass 45S5 particles (Sylc; OSspray Ltd, London, UK), and (3) resin with β-tricalcium phosphate-modified calcium silicate cement (HCAT-β) particles. The filler/resin ratio was 40/60 wt%. The specimens were stored in artificial saliva, and the determination of C-terminal telopeptide (ICTP) was performed by radioimmunoassay after 24 hours, 1 week, and 4 weeks. Scanning electron microscopic analysis of dentin surfaces after 4 weeks of storage was also executed. Collagen degradation was prominent both in phosphoric acid and EDTA-treated dentin. Resin infiltration strongly reduced the MMP activity in demineralized dentin. Resin-containing Bioglass 45S5 particles exerted higher and more stable protection of collagen at all tested dentin states and time points. HCAT-β induced collagen protection from MMPs only in EDTA-treated specimens. Dentin remineralization was achieved when dentin was infiltrated with the resin cements containing bioactive fillers. MMP degradation of dentin collagen is strongly reduced in resin-infiltrated dentin. The inclusion of Bioglass 45S5 particles exerted an additional protection of collagen during dentin remineralization. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  2. First International Conference on Lysophospholipids and Related Bioactive Lipids in Biology and Disease Sponsored by the Federation of American Societies of Experimental Biology

    Directory of Open Access Journals (Sweden)

    Edward J. Goetzl

    2001-01-01

    Full Text Available The First International Conference on “Lysophospholipids and Related Bioactive Lipids in Biology and Diseases” was held in Tucson, AZ on June 10�14, 2001, under the sponsorship of the Federation of American Societies of Experimental Biology (FASEB. More than 100 scientists from 11 countries discussed the recent results of basic and clinical research in the broad biology of this emerging field. Immense progress was reported in defining the biochemistry of generation and biology of cellular effects of the bioactive lysophospholipids (LPLs. These aspects of LPLs described at the conference parallel in many ways those of the eicosanoid mediators, such as prostaglandins and leukotrienes. As for eicosanoids, the LPLs termed lysophosphatidic acid (LPA and sphingosine 1-phosphate (S1P are produced enzymatically from phospholipid precursors in cell membranes and act on cells at nanomolar concentrations through subfamilies of receptors of the G protein–coupled superfamily. The rate-limiting steps in production of LPLs were reported to be controlled by specific phospholipases for LPA and sphingosine kinases for S1P. The receptor subfamilies formerly were designated endothelial differentiation gene-encoded receptors or Edg Rs for their original discovery in endothelial cells. A currently active nomenclature committee at this conference suggested the ligand-based names: S1P1 = Edg-1, S1P2 = Edg-5, S1P3 = Edg-3, S1P4 = Edg-6, and S1P5 = Edg-8; LPA1 = Edg-2, LPA2 = Edg-4, and LPA3 = Edg-7 receptors. Several families of lysophospholipid phosphatases (LPPs have been characterized, which biodegrade LPA, whereas S1P is inactivated with similar rapidity by both a lyase and S1P phosphatases.

  3. GC-MS evaluation of fatty acid profile and lipid bioactive of partially hydrogenated cooking oil consumed in Pakistan

    International Nuclear Information System (INIS)

    Kandhroab, A.A.; Sherazi, S.T.H.; Mahesar, S.A.; Talpura, M.Y.; Bhutto, A.A.

    2010-01-01

    Evaluation of fatty acid profile including trans fat and lipid bioactive (tocopherol and sterol contents) of most commonly used vanaspati ghee and cooking oil brands was made by gas chromatography coupled with mass spectrometer detector (GC-MSD). Among the saturated fatty acids (SFA), palmitic and stearic acid were dominant fatty acids; the mean value of SFA in ghee and oil was 44.98 and 30.83%, respectively. Mean values of monounsaturated, polyunsaturated and trans fatty acids in ghee were 47.51, 7.49 and 8.08%, and in oil 49.26, 19.90 and 0.91%, respectively. alpha-tocopherol was the major tocopherol while campesterol, stigmasterol and sitosterol were main phytosterols in terms of their quantity. (author)

  4. Chemical Profiling and Bioactivity of Body Wall Lipids from Strongylocentrotus droebachiensis

    Directory of Open Access Journals (Sweden)

    Alexander N. Shikov

    2017-11-01

    Full Text Available The lipids from gonads and polyhydroxynaphthoquinone pigments from body walls of sea urchins are intensively studied. However, little is known about the body wall (BW lipids. Ethanol extract (55 °C contained about equal amounts of saturated (SaFA and monounsaturated fatty acids (MUFA representing 60% of total fatty acids, with myristic, palmitic and eicosenoic acids as major SaFAs and MUFAs, respectively. Non-methylene-interrupted dienes (13% were composed of eicosadienoic and docosadienoic acids. Long-chain polyunsaturated fatty acids (LC-PUFA included two main components, n6 arachidonic and n3 eicosapentaenoic acids, even with equal concentrations (15 μg/mg and a balanced n6/n3 PUFA ratio (0.86. The UPLC-ELSD analysis showed that a great majority of the lipids (80% in the ethanolic extract were phosphatidylcholine (60 μg/mg and phosphatidylethanolamine (40 μg/mg, while the proportion of neutral lipids remained lower than 20%. In addition, alkoxyglycerol derivatives—chimyl, selachyl, and batyl alcohols—were quantified. We have assumed that the mechanism of action of body wall lipids in the present study is via the inhibition of MAPK p38, COX-1, and COX-2. Our findings open the prospective to utilize this lipid fraction as a source for the development of drugs with anti-inflammatory activity.

  5. Water soluble bioactives of nacre mediate antioxidant activity and osteoblast differentiation.

    Directory of Open Access Journals (Sweden)

    Ratna Chaturvedi

    Full Text Available The water soluble matrix of nacre is a proven osteoinductive material. In spite of the differences in the biomolecular compositions of nacre obtained from multiple species of oysters, the common biochemical properties of those principles substantiate their biological activity. However, the mechanism by which nacre stimulates bone differentiation remains largely unknown. Since the positive impact of antioxidants on bone metabolism is well acknowledged, in this study we investigated the antioxidant potential of a water soluble matrix (WSM obtained from the nacre of the marine oyster Pinctada fucata, which could regulate its osteoblast differentiation activity. Enhanced levels of ALP activity observed in pre-osteoblast cells upon treatment with WSM, suggested the induction of bone differentiation events. Furthermore, bone nodule formation and up-regulation of bone differentiation marker transcripts, i.e. collagen type-1 and osteocalcin by WSM confirmed its ability to induce differentiation of the pre-osteoblasts into mature osteoblasts. Remarkably, same WSM fraction upon pre-treatment lowered the H2O2 and UV-B induced oxidative damages in keratinocytes, thus indicating the antioxidant potential of WSM. This was further confirmed from the in vitro scavenging of ABTS and DPPH free radicals and inhibition of lipid peroxidation by WSM. Together, these results indicate that WSM poses both antioxidant potential and osteoblast differentiation property. Thus, bioactivities associated with nacre holds potential in the development of therapeutics for bone regeneration and against oxidative stress induced damages in cells.

  6. Optimization of cationic lipid mediated gene transfer: structure-function, physico-chemical, and cellular studies.

    Science.gov (United States)

    Carrière, Marie; Tranchant, Isabelle; Niore, Pierre-Antoine; Byk, Gerardo; Mignet, Nathalie; Escriou, Virginie; Scherman, Daniel; Herscovici, Jean

    2002-01-01

    The rationale design aimed at the enhancement of cationic lipid mediated gene transfer is discussed. These improvements are based on the straight evaluation of the structure-activity relationship and on the introduction of new structures. Much attention have been given to the supramolecular structures of the lipid/DNA complexes, to the effect of serum on gene transfer and to the intracellular trafficking of the lipoplexes. Finally new avenue using reducible cationic lipids has been discussed.

  7. Microencapsulation of nanoemulsions: novel Trojan particles for bioactive lipid molecule delivery.

    Science.gov (United States)

    Li, Xiang; Anton, Nicolas; Ta, Thi Minh Chau; Zhao, Minjie; Messaddeq, Nadia; Vandamme, Thierry F

    2011-01-01

    Nanoemulsions consist of very stable nanodroplets of oil dispersed in an aqueous phase, typically below 300 nm in size. They can be used to obtain a very fine, homogeneous dispersion of lipophilic compounds in water, thus facilitating their handling and use in nanomedicine. However, the drawback is that they are suspended in an aqueous media. This study proposes a novel technique for drying lipid nanoemulsion suspensions to create so-called Trojan particles, ie, polymer microparticles (around 2 μm) which very homogeneously "entrap" the nano-oil droplets (around 150 nm) in their core. Microencapsulation of the nanoemulsions was performed using a spray-drying process and resulted in a dried powder of microparticles. By using a low-energy nanoemulsification method and relatively gentle spray-drying, the process was well suited to sensitive molecules. The model lipophilic molecule tested was vitamin E acetate, encapsulated at around 20% in dried powder. We showed that the presence of nanoemulsions in solution before spray-drying had a significant impact on microparticle size, distribution, and morphology. However, the process itself did not destroy the oil nanodroplets, which could easily be redispersed when the powder was put back in contact with water. High-performance liquid chromatography follow-up of the integrity of the vitamin E acetate showed that the molecules were intact throughout the process, as well as when conserved in their dried form. This study proposes a novel technique using a spray-drying process to microencapsulate nanoemulsions. The multiscale object formed, so-called Trojan microparticles, were shown to successfully encapsulate, protect, and release the lipid nanodroplets.

  8. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras

    OpenAIRE

    Das, Anusuya; Segar, Claire E.; Chu, Yihsuan; Wang, Tiffany W.; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C.; Cui, Quanjun; Botchwey, Edward A.

    2015-01-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to lo...

  9. Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Ole A Andreassen

    Full Text Available Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS to investigate shared single nucleotide polymorphisms (SNPs between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals, applying new False Discovery Rate (FDR methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG, low density lipoproteins (LDL, high density lipoproteins (HDL] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis. We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88, LDL (n = 87 and HDL (n = 52. Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2 and intestinal host-microbe interactions (e.g. ATG16L1. We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

  10. Characterization of fatty acids, bioactive lipids, and radical scavenging activity of Canterbury bells seed oil

    Directory of Open Access Journals (Sweden)

    Hassanien, M. F.R.

    2014-06-01

    Full Text Available The aim of this study was to characterize the chemical composition and radical scavenging activity of Canterbury bells (Campanula medium seed oil. C. medium seeds contained 9.2% extractable oil. The lipid classes, fatty acids, phytosterol and tocopherol composition of C. medium seed oil were determined. The amount of neutral lipids in the oil was the highest, followed by glycolipids and phospholipids. Linoleic and oleic were the main fatty acids. C. medium oil is characterized by high levels of phytosterols and β-sitosterol was the main compound. β-Tocopherol constituted 42.5% of the total tocopherol content followed by γ-tocopherol. The radical scavenging activity (RSA toward 1,1-diphenyl-2-picrylhydrazyl (DPPH radicals and galvinoxyl radicals of C. medium oil were higher than those of extra virgin olive oil. The diverse potential uses of C. medium oil may make this plant industrially important.El objetivo de este estudio fue caracterizar la composición química y la actividad de captación de radicales de aceites de semillas de campanillas de Canterbury (Campanula medium. Las semillas de C. medium contenían 9,2 % de aceite extraíble. Se determinó la composición de las diferentes clases de lípidos, ácidos grasos, fitoesteroles y tocoferoles. La cantidad de lípidos neutros en el aceite fue mayoritario, seguido de glicolípidos y fosfolípidos. Linoleico y oleico fueron los ácidos grasos principales. El aceite de C. medium se caracteriza por altos niveles de fitoesteroles y β-sitosterol fue el compuesto principal. β-tocoferol constituía 42,5 % del contenido total de tocoferol seguido de γ-tocoferol. La actividad de captación de radicales (RSA a 1,1-difenil-2- picrilhidrazil (DPPH y radicales galvinoxil de C. medium fueron superiores a las de aceite de oliva virgen extra. Los diversos usos potenciales de los aceites de C. medium pueden hacer que esta planta pueda ser importante industrialmente.

  11. LRRK2 mediated Rab8a phosphorylation promotes lipid storage.

    Science.gov (United States)

    Yu, Miao; Arshad, Muhammad; Wang, Wenmin; Zhao, Dongyu; Xu, Li; Zhou, Linkang

    2018-02-27

    Several mutations in leucine rich repeat kinase 2 (LRRK2) gene have been associated with pathogenesis of Parkinson's disease (PD), a neurodegenerative disorder marked by resting tremors, and rigidity, leading to Postural instability. It has been revealed that mutations that lead to an increase of kinase activity of LRRK2 protein are significantly associated with PD pathogenesis. Recent studies have shown that some Rab GTPases, especially Rab8, serve as substrates of LRRK2 and undergo phosphorylation in its switch II domain upon interaction. Current study was performed in order to find out the effects of the phosphorylation of Rab8 and its mutants on lipid metabolism and lipid droplets growth. The phosphorylation status of Rab8a was checked by phos-tag gel. Point mutant construct were generated to investigate the function of Rab8a. 3T3L1 cells were transfected with indicated plasmids and the lipid droplets were stained with Bodipy. Fluorescent microscopy experiments were performed to examine the sizes of lipid droplets. The interactions between Rab8a and Optineurin were determined by immunoprecipitation and western blot. Our assays demonstrated that Rab8a was phosphorylated by mutated LRRK2 that exhibits high kinase activity. Phosphorylation of Rab8a on amino acid residue T72 promoted the formation of large lipid droplets. T72D mutant of Rab8a had higher activity to promote the formation of large lipid droplets compared with wild type Rab8a, with increase in average diameter of lipid droplets from 2.10 μm to 2.46 μm. Moreover, phosphorylation of Rab8a weakened the interaction with its effector Optineurin. Y1699C mutated LRRK2 was able to phosphorylate Rab8a and phosphorylation of Rab8a on site 72 plays important role in the fusion and enlargement of lipid droplets. Taken together, our study suggests an indirect relationship between enhanced lipid storage capacity and PD pathogenesis.

  12. Phloem proteomics reveals new lipid-binding proteins with a putative role in lipid-mediated signaling

    Directory of Open Access Journals (Sweden)

    Allison Marie Barbaglia

    2016-04-01

    Full Text Available Global climate changes inversely affect our ability to grow the food required for an increasing world population. To combat future crop loss due to abiotic stress, we need to understand the signals responsible for changes in plant development and the resulting adaptations, especially the signaling molecules traveling long-distance through the plant phloem. Using a proteomics approach, we had identified several putative lipid-binding proteins in the phloem exudates. Simultaneously, we identified several complex lipids as well as jasmonates. These findings prompted us to propose that phloem (phospho- lipids could act as long-distance developmental signals in response to abiotic stress, and that they are released, sensed, and moved by phloem lipid-binding proteins (Benning et al., 2012. Indeed, the proteins we identified include lipases that could release a signaling lipid into the phloem, putative receptor components, and proteins that could mediate lipid-movement. To test this possible protein-based lipid-signaling pathway, three of the proteins, which could potentially act in a relay, are characterized here: (I a putative GDSL-motif lipase (II a PIG-P-like protein, with a possible receptor-like function; (III and PLAFP (phloem lipid-associated family protein, a predicted lipid-binding protein of unknown function. Here we show that all three proteins bind lipids, in particular phosphatidic acid (PtdOH, which is known to participate in intracellular stress signaling. Genes encoding these proteins are expressed in the vasculature, a prerequisite for phloem transport. Cellular localization studies show that the proteins are not retained in the endoplasmic reticulum but surround the cell in a spotted pattern that has been previously observed with receptors and plasmodesmatal proteins. Abiotic signals that induce the production of PtdOH also regulate the expression of GDSL-lipase and PLAFP, albeit in opposite patterns. Our findings suggest that while

  13. Bioactive potential of Vitis labrusca L. grape juices from the Southern Region of Brazil: phenolic and elemental composition and effect on lipid peroxidation in healthy subjects.

    Science.gov (United States)

    Toaldo, Isabela Maia; Cruz, Fernanda Alves; Alves, Tatiana de Lima; de Gois, Jefferson Santos; Borges, Daniel L G; Cunha, Heloisa Pamplona; da Silva, Edson Luiz; Bordignon-Luiz, Marilde T

    2015-04-15

    Grapes are rich in polyphenols with biologically active properties. Although the bioactive potential of grape constituents are frequently reported, the effects of Brazilian Vitis labrusca L. grape juices ingestion have not been demonstrated in humans. This study identified the phenolic and elemental composition of red and white grape juices and the effect of organic and conventional red grape juice consumption on lipid peroxidation in healthy individuals. Concentrations of anthocyanins, flavanols and phenolic acids and the in vitro antioxidant activity were significantly higher in the organic juice. The macro-elements K, Ca, Na and Mg were the most abundant minerals in all juices. The acute consumption of red grape juices promoted significant decrease of lipid peroxides in serum and TBARS levels in plasma. It is concluded that red V. labrusca L. grape juices produced in Southern Brazil showed lipid peroxidation inhibition abilities in healthy subjects, regardless of the cultivation system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport.

    Science.gov (United States)

    Alva, Vikram; Lupas, Andrei N

    2016-08-01

    The tubular lipid-binding (TULIP) superfamily has emerged in recent years as a major mediator of lipid sensing and transport in eukaryotes. It currently encompasses three protein families, SMP-like, BPI-like, and Takeout-like, which share a common fold. This fold consists of a long helix wrapped in a highly curved anti-parallel β-sheet, enclosing a central, lipophilic cavity. The SMP-like proteins, which include subunits of the ERMES complex and the extended synaptotagmins (E-Syts), appear to be mainly located at membrane contacts sites (MCSs) between organelles, mediating inter-organelle lipid exchange. The BPI-like proteins, which include the bactericidal/permeability-increasing protein (BPI), the LPS (lipopolysaccharide)-binding protein (LBP), the cholesteryl ester transfer protein (CETP), and the phospholipid transfer protein (PLTP), are either involved in innate immunity against bacteria through their ability to sense lipopolysaccharides, as is the case for BPI and LBP, or in lipid exchange between lipoprotein particles, as is the case for CETP and PLTP. The Takeout-like proteins, which are comprised of insect juvenile hormone-binding proteins and arthropod allergens, transport, where known, lipid hormones to target tissues during insect development. In all cases, the activity of these proteins is underpinned by their ability to bind large, hydrophobic ligands in their central cavity and segregate them away from the aqueous environment. Furthermore, where they are involved in lipid exchange, recent structural studies have highlighted their ability to establish lipophilic, tubular channels, either between organelles in the case of SMP domains or between lipoprotein particles in the case of CETP. Here, we review the current knowledge on the structure, versatile functions, and evolution of the TULIP superfamily. We propose a deep evolutionary split in this superfamily, predating the Last Eukaryotic Common Ancestor, between the SMP-like proteins, which act on

  15. Programmable fusion of liposomes mediated by lipidated PNA

    DEFF Research Database (Denmark)

    Rabe, A; Löffler, P M G; Ries, O

    2017-01-01

    We recently reported a DNA-programmed fusion cascade enabling the use of liposomes as nanoreactors for compartmentalized chemical reactions. This communication reports an alternative and robust strategy based on lipidated peptide nucleic acids (LiPs). LiPs enabled fusion of liposomes with remarka...... with remarkable 31% efficiency at 50 °C with low leakage (5%)....

  16. Molecular modeling of proteinlike inclusions in lipid bilayers: lipid-mediated interactions.

    Science.gov (United States)

    Kik, Richard A; Leermakers, Frans A M; Kleijn, J Mieke

    2010-02-01

    We investigated the insertion of transmembrane structures in a lipid bilayer and their interactions using self-consistent field theory. The lipids are coarse-grained on a united-atom level and consist of a phosphatidylcholinelike headgroup and two hydrophobic tails. The inclusions, acting as simple models for proteins that span biological membranes, are rigid rods (radius R ) with a hydrophobic surface and hydrophilic end caps. The insertion free energy Omega of an individual rod is strongly regulated by the affinity between its hydrophobic surface and the lipid tails. This affinity also controls the best match of the hydrophobic length of the rod with that of the bilayer. The line tension tau(=Omega/2piR) is practically independent of R . The perturbations in the bilayer as a function of distance from the inclusion, have the shape of a damped oscillation. The wavelength and decay length are related to the elastic properties of the bilayer and do not depend on R . These results are used to analyze how the lipid matrix affects the interaction between transmembrane objects, for computational reasons considering the limit of R-->infinity . Contributions on different length scales can be distinguished: (i) a long-range elastic interaction, which is an exponentially decaying oscillation; (ii) an exponentially decaying repulsion on an intermediate length scale, resulting from the loss of conformational entropy of the lipid tails; and (iii) a short-range interaction due to the finite compressibility of the lipid tails, which manifests either as a depletion attraction if there is no affinity between the tails and the inclusions' surface or, otherwise, as an oscillatory structural force.

  17. Agrobacterium rhizogenes mediated transformation of Rhodiola sp. – an approach to enhance the level of bioactive compounds

    DEFF Research Database (Denmark)

    Møller Hansen, Martin; Lauridsen, Uffe Bjerre; Hegelund, Josefine Nymark

    Agrobacterium rhizogenes mediated transformation of Rhodiola sp. – an approach to enhance the level of bioactive compounds. Martin Møller Hansen1, Uffe Bjerre Lauridsen2, Josefine Nymark Hegelund3, Renate Müller4, Jihong Liu Clarke5, Henrik Lütken6 University of Copenhagen, Faculty of Science...... to wild type roots. The purpose of this study is to obtain HRs containing rol-genes from Rhodiola sp. for future sustainable production in bioreactors. Materials and Methods Whole stems of R. rosea and two accessions of R. pachyclados were sterilized with ethanol and NaOCl. The stems were then cut...

  18. Iron-mediated lipid oxidation in 70% fish oil-in-ater emulsions

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte

    2012-01-01

    The objective of this study was to investigate the protective effect of five different emulsifiers on iron‐mediated lipid oxidation in 70% fish oil‐in‐water emulsions. The emulsifiers were either based on protein (whey protein isolate and sodium caseinate) or based on phospholipid (soy lecithin...... and two milk phospholipids with different phospholipid contents, MPL20 and MPL75). Lipid oxidation was studied at pH 4.5 and 7.0, and results were compared to lipid oxidation in neat fish oil. Results showed that all emulsions oxidised more than neat oil. Furthermore, emulsions prepared with proteins...

  19. Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.

    Directory of Open Access Journals (Sweden)

    Marco Sisignano

    Full Text Available Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including a number of oxidized lipids, some of which serve endogenous modulators of sensory TRP-channels. These lipids are eicosanoids of the arachidonic acid and linoleic acid pathway, as well as lysophophatidic acids (LPAs. However, their regulation pattern during inflammatory pain and their contribution to peripheral sensitization is still unclear. Here, we used the UVB-model for inflammatory pain to investigate alterations of lipid concentrations at the site of inflammation, the dorsal root ganglia (DRGs as well as the spinal dorsal horn and quantified 21 lipid species from five different lipid families at the peak of inflammation 48 hours post irradiation. We found that known proinflammatory lipids as well as lipids with unknown roles in inflammatory pain to be strongly increased in the skin, whereas surprisingly little changes of lipid levels were seen in DRGs or the dorsal horn. Importantly, although there are profound differences between the number of cytochrome (CYP genes between mice and rats, CYP-derived lipids were regulated similarly in both species. Since TRPV1 agonists such as LPA 18∶1, 9- and 13-HODE, 5- and 12-HETE were elevated in the skin, they may contribute to thermal hyperalgesia and mechanical allodynia during UVB-induced inflammatory pain. These results may explain why some studies show relatively weak analgesic effects of cyclooxygenase inhibitors in UVB-induced skin inflammation, as they do not inhibit synthesis of other proalgesic lipids such as LPA 18∶1, 9-and 13-HODE and HETEs.

  20. The Role of Lipid Competition for Endosymbiont-Mediated Protection against Parasitoid Wasps in Drosophila

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    Juan C. Paredes

    2016-07-01

    Full Text Available Insects commonly harbor facultative bacterial endosymbionts, such as Wolbachia and Spiroplasma species, that are vertically transmitted from mothers to their offspring. These endosymbiontic bacteria increase their propagation by manipulating host reproduction or by protecting their hosts against natural enemies. While an increasing number of studies have reported endosymbiont-mediated protection, little is known about the mechanisms underlying this protection. Here, we analyze the mechanisms underlying protection from parasitoid wasps in Drosophila melanogaster mediated by its facultative endosymbiont Spiroplasma poulsonii. Our results indicate that S. poulsonii exerts protection against two distantly related wasp species, Leptopilina boulardi and Asobara tabida. S. poulsonii-mediated protection against parasitoid wasps takes place at the pupal stage and is not associated with an increased cellular immune response. In this work, we provide three important observations that support the notion that S. poulsonii bacteria and wasp larvae compete for host lipids and that this competition underlies symbiont-mediated protection. First, lipid quantification shows that both S. poulsonii and parasitoid wasps deplete D. melanogaster hemolymph lipids. Second, the depletion of hemolymphatic lipids using the Lpp RNA interference (Lpp RNAi construct reduces wasp success in larvae that are not infected with S. poulsonii and blocks S. poulsonii growth. Third, we show that the growth of S. poulsonii bacteria is not affected by the presence of the wasps, indicating that when S. poulsonii is present, larval wasps will develop in a lipid-depleted environment. We propose that competition for host lipids may be relevant to endosymbiont-mediated protection in other systems and could explain the broad spectrum of protection provided.

  1. Interface-mediation of lipid bilayer organization and dynamics.

    Science.gov (United States)

    Mize, Hannah E; Blanchard, G J

    2016-06-22

    We report on the morphology and dynamics of planar supported lipid bilayer structures as a function of pH and ionic strength of the aqueous overlayer. Supported lipid bilayers composed of three components (phosphocholine, sphingomyelin and cholesterol) are known to exhibit phase segregation, with the characteristic domain sizes dependent on the amount and identity of each constituent, and the composition of the aqueous overlayer in contact with the bilayer. We report on fluorescence anisotropy decay imaging measurements of a rhodamine chromophore tethered to the headgroup of a phosphoethanolamine, where anisotropy decay images were acquired as a function of solution overlayer pH and ionic strength. The data reveal a two-component anisotropy decay under all conditions, with the faster time constant being largely independent of pH and ionic strength and the slower component depending on pH and ionic strength in different manners. For liposomes of the same composition, a single exponential anisotropy decay was seen. We interpret this difference in terms of bilayer curvature and support surface-bilayer interactions, and the pH and ionic strength dependencies in terms of ionic screening and protonation in the bilayer headgroup region.

  2. Dual peptide-mediated targeted delivery of bioactive siRNAs to oral cancer cells in vivo.

    Science.gov (United States)

    Alexander-Bryant, Angela A; Zhang, Haiwen; Attaway, Christopher C; Pugh, William; Eggart, Laurence; Sansevere, Robert M; Andino, Lourdes M; Dinh, Lu; Cantini, Liliana P; Jakymiw, Andrew

    2017-09-01

    Despite significant advances in cancer treatment, the prognosis for oral cancer remains poor in comparison to other cancer types, including breast, skin, and prostate. As a result, more effective therapeutic modalities are needed for the treatment of oral cancer. Consequently, in the present study, we examined the feasibility of using a dual peptide carrier approach, combining an epidermal growth factor receptor (EGFR)-targeting peptide with an endosome-disruptive peptide, to mediate targeted delivery of small interfering RNAs (siRNAs) into EGFR-overexpressing oral cancer cells and induce silencing of the targeted oncogene, cancerous inhibitor of protein phosphatase 2A (CIP2A). Fluorescence microscopy, real-time PCR, Western blot analysis, and in vivo bioimaging of mice containing orthotopic xenograft tumors were used to examine the ability of the dual peptide carrier to mediate specific delivery of bioactive siRNAs into EGFR-overexpressing oral cancer cells/tissues. Co-complexation of the EGFR-targeting peptide, GE11R9, with the endosome-disruptive 599 peptide facilitated the specific uptake of siRNAs into oral cancer cells overexpressing EGFR in vitro with optimal gene silencing observed at a 60:30:1 (GE11R9:599:siRNA) molar ratio. Furthermore, when administered systemically to mice bearing xenograft oral tumors, this dual peptide complex mediated increased targeted delivery of siRNAs into tumor tissues in comparison to the 599 peptide alone and significantly enhanced CIP2A silencing. Herein we provide the first report demonstrating the clinical potential of a dual peptide strategy for siRNA-based therapeutics by synergistically mediating the effective targeting and delivery of bioactive siRNAs into EGFR-overexpressing oral cancer cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Exogenous estrogen as mediator of racial differences in bioactive insulin-like growth factor-I levels among postmenopausal women.

    Science.gov (United States)

    Jung, Su Yon; Vitolins, Mara Z; Paskett, Electra D; Chang, Shine

    2015-04-01

    The role of exogenous estrogen use in racial differences in insulin-like growth factor-I (IGF-I) levels which affect cancer risk is unclear. We investigated whether the relationship between race and circulating bioactive IGF-I proteins was mediated by exogenous estrogen and the extent to which exogenous estrogen influenced the race-IGF-I relationship in postmenopausal women. This cross-sectional study included 636 white and 133 African American postmenopausal women enrolled in an ancillary study of the Women's Health Initiative Observational Study. To assess exogenous estrogen use (nonusers [n = 262] vs users [n = 507]) as a mediator of the race-IGF-I relationship, we used the Baron-Kenny method and an estimation of the proportional change in the odd ratios for IGF-I levels on race plus a bootstrapping test for the significance of the mediation effect. Compared with white women, African American women were more likely to have high IGF-I levels and less likely to use exogenous estrogen. After accounting for race, estrogen nonusers had higher IGF-I levels than estrogen users did. Among oral contraceptive ever users, exogenous estrogen had a strong mediation effect (67%; p = .018) in the race-IGF-I relationship. In the women with a history of hypertension, exogenous estrogen explained racial differences in IGF-I levels to a modest degree (23%; p = .029). Exogenous estrogen use has a potentially important role in disparities in IGF-I bioactivity between postmenopausal African American and white women. A history of oral contraceptive use and hypertension may be part of the interconnected hormonal pathways related to racial differences in IGF-I levels. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Effects of stimulation technique, anatomical region and time on human sweat lipid mediator profiles.

    Science.gov (United States)

    Few studies compare sampling protocol effect on sweat composition. Here we evaluate the impact of sweat stimulation mode and site of collection on lipid mediator composition. Sweat from healthy males (n = 7) was collected weekly for three weeks from the volar forearm following either pilocarpine ion...

  5. Lipid vesicle-mediated affinity chromatography using magnetic activated cell sorting (LIMACS): a novel method to analyze protein-lipid interaction.

    Science.gov (United States)

    Bieberich, Erhard

    2011-04-26

    The analysis of lipid protein interaction is difficult because lipids are embedded in cell membranes and therefore, inaccessible to most purification procedures. As an alternative, lipids can be coated on flat surfaces as used for lipid ELISA and Plasmon resonance spectroscopy. However, surface coating lipids do not form microdomain structures, which may be important for the lipid binding properties. Further, these methods do not allow for the purification of larger amounts of proteins binding to their target lipids. To overcome these limitations of testing lipid protein interaction and to purify lipid binding proteins we developed a novel method termed lipid vesicle-mediated affinity chromatography using magnetic-activated cell sorting (LIMACS). In this method, lipid vesicles are prepared with the target lipid and phosphatidylserine as the anchor lipid for Annexin V MACS. Phosphatidylserine is a ubiquitous cell membrane phospholipid that shows high affinity to the protein Annexin V. Using magnetic beads conjugated to Annexin V the phosphatidylserine-containing lipid vesicles will bind to the magnetic beads. When the lipid vesicles are incubated with a cell lysate the protein binding to the target lipid will also be bound to the beads and can be co-purified using MACS. This method can also be used to test if recombinant proteins reconstitute a protein complex binding to the target lipid. We have used this method to show the interaction of atypical PKC (aPKC) with the sphingolipid ceramide and to co-purify prostate apoptosis response 4 (PAR-4), a protein binding to ceramide-associated aPKC. We have also used this method for the reconstitution of a ceramide-associated complex of recombinant aPKC with the cell polarity-related proteins Par6 and Cdc42. Since lipid vesicles can be prepared with a variety of sphingo- or phospholipids, LIMACS offers a versatile test for lipid-protein interaction in a lipid environment that resembles closely that of the cell membrane

  6. Lipid-Mediated Clusters of Guest Molecules in Model Membranes and Their Dissolving in the Presence of Lipid Rafts.

    Science.gov (United States)

    Kardash, Maria E; Dzuba, Sergei A

    2017-05-25

    The clustering of molecules is an important feature of plasma membrane organization. It is challenging to develop methods for quantifying membrane heterogeneities because of their transient nature and small size. Here, we obtained evidence that transient membrane heterogeneities can be frozen at cryogenic temperatures which allows the application of solid-state experimental techniques sensitive to the nanoscale distance range. We employed the pulsed version of electron paramagnetic resonance (EPR) spectroscopy, the electron spin echo (ESE) technique, for spin-labeled molecules in multilamellar lipid bilayers. ESE decays were refined for pure contribution of spin-spin magnetic dipole-dipolar interaction between the labels; these interactions manifest themselves at a nanometer distance range. The bilayers were prepared from different types of saturated and unsaturated lipids and cholesterol (Chol); in all cases, a small amount of guest spin-labeled substances 5-doxyl-stearic-acid (5-DSA) or 3β-doxyl-5α-cholestane (DChl) was added. The local concentration found of 5-DSA and DChl molecules was remarkably higher than the mean concentration in the bilayer, evidencing the formation of lipid-mediated clusters of these molecules. To our knowledge, formation of nanoscale clusters of guest amphiphilic molecules in biological membranes is a new phenomenon suggested only recently. Two-dimensional 5-DSA molecular clusters were found, whereas flat DChl molecules were found to be clustered into stacked one-dimensional structures. These clusters disappear when the Chol content is varied between the boundaries known for lipid raft formation at room temperatures. The room temperature EPR evidenced entrapping of DChl molecules in the rafts.

  7. Therapeutic Applicability of Anti-Inflammatory and Proresolving Polyunsaturated Fatty Acid-Derived Lipid Mediators

    Directory of Open Access Journals (Sweden)

    Gerard L. Bannenberg

    2010-01-01

    Full Text Available The enzymatic oxygenation of polyunsaturated fatty acids by lipoxygenases and cyclo-oxygenases is a resourceful mode of formation of specific autacoids that regulate the extent and pace of the inflammatory response. Arachidonate-derived eicosanoids, such as lipoxin A4, prostaglandin (PGD2, PGF2α, PGE2, and PGD2-derived cyclopentenones exert specific roles in counter-regulating inflammation and turning on resolution. Recently recognized classes of autacoids derived from long-chain ω-3 polyunsaturated fatty acids, the E- and D-series resolvins, protectin D1, and maresin 1, act as specialized mediators to dampen inflammation actively, afford tissue protection, stimulate host defense, and activate resolution. It is held that counter-regulatory lipid mediators and the specific molecular pathways activated by such endogenous agonists may be suitable for pharmacological use in the treatment of inflammatory disease. The anti-inflammatory drug aspirin is a striking example of a drug that is able to act in such a manner, namely through triggering the formation of 15-epi-lipoxin A4 and aspirin-triggered resolvins. Different aspects of the therapeutic applicability of lipid mediators have been addressed here, and indicate that the development of innovative pharmacotherapy based on anti-inflammatory and proresolution lipid mediators presents novel prospects for the treatment of inflammatory disease.

  8. Emerging roles of eosinophils and eosinophil-derived lipid mediators in the resolution of inflammation

    Directory of Open Access Journals (Sweden)

    Yosuke eIsobe

    2012-08-01

    Full Text Available Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. Once thought to be a passive process, the resolution of inflammation is now shown to involve active biochemical programs that enable inflamed tissues to return to homeostasis. The mechanisms by which acute inflammation is resolved are of interest, and research in recent years has uncovered new endogenous anti-inflammatory and pro-resolving lipid mediators (i.e. lipoxins, resolvins, protectin, and maresin generated from polyunsaturated fatty acids (PUFAs. This review presents new insights into the cellular and molecular mechanisms of inflammatory resolution, especially the roles of eosinophils, and a series of omega-3 PUFA derived anti-inflammatory lipid mediators that they generate.

  9. Lipid Metabolism, Apoptosis and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Chunfa Huang

    2015-01-01

    Full Text Available Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

  10. Glycation and transglutaminase mediated glycosylation of fish gelatin peptides with glucosamine enhance bioactivity.

    Science.gov (United States)

    Hong, Pui Khoon; Gottardi, Davide; Ndagijimana, Maurice; Betti, Mirko

    2014-01-01

    A mixture of novel glycopeptides from glycosylation between cold water fish skin gelatin hydrolysates and glucosamine (GlcN) via transglutaminase (TGase), as well as glycation between fish gelatin hydrolysate and GlcN were identified by their pattern of molecular distribution using MALDI-TOF-MS. Glycated/glycosylated hydrolysates showed superior bioactivity to their original hydrolysates. Alcalase-derived fish skin gelatin hydrolysate glycosylated with GlcN in the presence of TGase at 25°C (FAT25) possessed antioxidant activity when tested in a linoleic acid oxidation system, when measured according to its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and when tested at the cellular level with human hepatocarcinoma (HepG2) cells as target cells. In addition, Alcalase-derived glycosylated hydrolysates showed specificity toward the inhibition of Escherichia coli (E. coli). The Flavourzyme-derived glycopeptides prepared at 37°C (FFC37 and FFT37) showed better DPPH scavenging activity than their native hydrolysates. The glycated Flavourzyme-derived hydrolysates were found to act as potential antimicrobial agents when incubated with E. coli and Bacillus subtilis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Dissolution of Lipid-Based Matrices in Simulated Gastrointestinal Solutions to Evaluate Their Potential for the Encapsulation of Bioactive Ingredients for Foods.

    Science.gov (United States)

    Raymond, Yves; Champagne, Claude P

    2014-01-01

    The goal of the study was to compare the dissolution of chocolate to other lipid-based matrices suitable for the microencapsulation of bioactive ingredients in simulated gastrointestinal solutions. Particles having approximately 750 μm or 2.5 mm were prepared from the following lipid-based matrices: cocoa butter, fractionated palm kernel oil (FPKO), chocolate, beeswax, carnauba wax, and paraffin. They were added to solutions designed to simulate gastric secretions (GS) or duodenum secretions (DS) at 37°C. Paraffin, carnauba wax, and bees wax did not dissolve in either the GS or DS media. Cocoa butter, FPKO, and chocolate dissolved in the DS medium. Cocoa butter, and to a lesser extent chocolate, also dissolved in the GS medium. With chocolate, dissolution was twice as fast as that with small particles (750 μm) as compared to the larger (2.5 mm) ones. With 750 μm particle sizes, 90% dissolution of chocolate beads was attained after only 60 minutes in the DS medium, while it took 120 minutes for 70% of FPKO beads to dissolve in the same conditions. The data are discussed from the perspective of controlled release in the gastrointestinal tract of encapsulated ingredients (minerals, oils, probiotic bacteria, enzymes, vitamins, and peptides) used in the development of functional foods.

  12. Dissolution of Lipid-Based Matrices in Simulated Gastrointestinal Solutions to Evaluate Their Potential for the Encapsulation of Bioactive Ingredients for Foods

    Directory of Open Access Journals (Sweden)

    Yves Raymond

    2014-01-01

    Full Text Available The goal of the study was to compare the dissolution of chocolate to other lipid-based matrices suitable for the microencapsulation of bioactive ingredients in simulated gastrointestinal solutions. Particles having approximately 750 μm or 2.5 mm were prepared from the following lipid-based matrices: cocoa butter, fractionated palm kernel oil (FPKO, chocolate, beeswax, carnauba wax, and paraffin. They were added to solutions designed to simulate gastric secretions (GS or duodenum secretions (DS at 37°C. Paraffin, carnauba wax, and bees wax did not dissolve in either the GS or DS media. Cocoa butter, FPKO, and chocolate dissolved in the DS medium. Cocoa butter, and to a lesser extent chocolate, also dissolved in the GS medium. With chocolate, dissolution was twice as fast as that with small particles (750 μm as compared to the larger (2.5 mm ones. With 750 μm particle sizes, 90% dissolution of chocolate beads was attained after only 60 minutes in the DS medium, while it took 120 minutes for 70% of FPKO beads to dissolve in the same conditions. The data are discussed from the perspective of controlled release in the gastrointestinal tract of encapsulated ingredients (minerals, oils, probiotic bacteria, enzymes, vitamins, and peptides used in the development of functional foods.

  13. ILDR2: an endoplasmic reticulum resident molecule mediating hepatic lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Kazuhisa Watanabe

    Full Text Available Ildr2, a modifier of diabetes susceptibility in obese mice, is expressed in most organs, including islets and hypothalamus, with reduced levels in livers of diabetes-susceptible B6.DBA mice congenic for a 1.8 Mb interval of Chromosome 1. In hepatoma and neuronal cells, ILDR2 is primarily located in the endoplasmic reticulum membrane. We used adenovirus vectors that express shRNA or are driven by the CMV promoter, respectively, to knockdown or overexpress Ildr2 in livers of wild type and ob/ob mice. Livers in knockdown mice were steatotic, with increased hepatic and circulating triglycerides and total cholesterol. Increased circulating VLDL, without reduction in triglyceride clearance suggests an effect of reduced hepatic ILDR2 on hepatic cholesterol clearance. In animals that overexpress Ildr2, hepatic triglyceride and total cholesterol levels were reduced, and strikingly so in ob/ob mice. There were no significant changes in body weight, energy expenditure or glucose/insulin homeostasis in knockdown or overexpressing mice. Knockdown mice showed reduced expression of genes mediating synthesis and oxidation of hepatic lipids, suggesting secondary suppression in response to increased hepatic lipid content. In Ildr2-overexpressing ob/ob mice, in association with reduced liver fat content, levels of transcripts related to neutral lipid synthesis and cholesterol were increased, suggesting "relief" of the secondary suppression imposed by lipid accumulation. Considering the fixed location of ILDR2 in the endoplasmic reticulum, we investigated the possible participation of ILDR2 in ER stress responses. In general, Ildr2 overexpression was associated with increases, and knockdown with decreases in levels of expression of molecular components of canonical ER stress pathways. We conclude that manipulation of Ildr2 expression in liver affects both lipid homeostasis and ER stress pathways. Given these reciprocal interactions, and the relatively extended time

  14. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers.

    Science.gov (United States)

    Lin, Chih-Hung; Chen, Chun-Han; Lin, Zih-Chan; Fang, Jia-You

    2017-04-01

    Chemical and enzymatic barriers in the gastrointestinal (GI) tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs) are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs. Copyright © 2017. Published by Elsevier B.V.

  15. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers

    Directory of Open Access Journals (Sweden)

    Chih-Hung Lin

    2017-04-01

    Full Text Available Chemical and enzymatic barriers in the gastrointestinal (GI tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs.

  16. The Mediator Complex MED15 Subunit Mediates Activation of Downstream Lipid-Related Genes by the WRINKLED1 Transcription Factor.

    Science.gov (United States)

    Kim, Mi Jung; Jang, In-Cheol; Chua, Nam-Hai

    2016-07-01

    The Mediator complex is known to be a master coordinator of transcription by RNA polymerase II, and this complex is recruited by transcription factors (TFs) to target promoters for gene activation or repression. The plant-specific TF WRINKLED1 (WRI1) activates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. However, no Mediator subunit has yet been identified that mediates WRI1 transcriptional activity. Promoter-β-glucuronidase fusion experiments showed that MEDIATOR15 (MED15) is expressed in the same cells in the embryo as WRI1. We found that the Arabidopsis (Arabidopsis thaliana) MED15 subunit of the Mediator complex interacts directly with WRI1 in the nucleus. Overexpression of MED15 or WRI1 increased transcript levels of WRI1 target genes involved in glycolysis and fatty acid biosynthesis; these genes were down-regulated in wild-type or WRI1-overexpressing plants by silencing of MED15 However, overexpression of MED15 in the wri1 mutant also increased transcript levels of WRI1 target genes, suggesting that MED15 also may act with other TFs to activate downstream lipid-related genes. Chromatin immunoprecipitation assays confirmed the association of MED15 with six WRI1 target gene promoters. Additionally, silencing of MED15 resulted in reduced fatty acid content in seedlings and mature seeds, whereas MED15 overexpression increased fatty acid content in both developmental stages. Similar results were found in wri1 mutant and WRI1 overexpression lines. Together, our results indicate that the WRI1/MED15 complex transcriptionally regulates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. © 2016 American Society of Plant Biologists. All Rights Reserved.

  17. Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

    International Nuclear Information System (INIS)

    Singaravelu, Ragunath; Lyn, Rodney K.; Srinivasan, Prashanth; Delcorde, Julie; Steenbergen, Rineke H.; Tyrrell, D. Lorne; Pezacki, John P.

    2013-01-01

    Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway

  18. Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Singaravelu, Ragunath [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Lyn, Rodney K. [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Srinivasan, Prashanth [National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Delcorde, Julie [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Steenbergen, Rineke H.; Tyrrell, D. Lorne [Department of Medical Microbiology and Immunology, University of Alberta (Canada); Li Ka Shing Institute of Virology, Katz Centre for Pharmacy and Health Research, Edmonton, Alberta T6G 2S2 (Canada); Pezacki, John P., E-mail: John.Pezacki@nrc-cnrc.gc.ca [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada)

    2013-11-15

    Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway.

  19. Selective identification of specialized pro-resolving lipid mediators from their biosynthetic double di-oxygenation isomers.

    Science.gov (United States)

    Hansen, Trond V; Dalli, Jesmond; Serhan, Charles N

    The n-3 polyunsaturated fatty acids are substrates for lipoxygenases and cyclooxygenases. During inflammatory processes, these enzymes form several distinct families of oxygenated polyunsaturated fatty acids coined specialized pro-resolving lipid mediators. Structural elucidation of these natural products using LC-MS/MS based metabololipidomics with the pico- to nanogram amounts of biosynthetic material available have been performed. The specialized pro-resolving lipid mediators display stereospecific and potent anti-inflammatory and pro-resolving actions. Most often the different families among these mediators are chemically characterized by two or three chiral, secondary alcohols, separated by either an E,E,Z -triene or an E,Z,E,E -tetraenemoiety. The lipoxygenases also form other oxygenated polyunsaturated natural products, coined double di-oxygenation products, that are constitutional isomers of the protectin and maresin families of specialized pro-resolving lipid mediators. Very often these products exhibit similar chromatographic properties and mass spectrometrical fragment ions as the pro-resolving mediators. In addition, the double di-oxygenation products are sometimes formed in larger amounts than the specialized pro-resolving lipid mediators. Thus, it is not always possible to distinguish between the specialized pro-resolving mediators and their double di-oxygenation isomers in biological systems, using LC/MS-based techniques. Herein, a convenient and easy-to-use protocol to meet this challenge is presented.

  20. Surface Lipids as Multifunctional Mediators of Skin Responses to Environmental Stimuli

    Directory of Open Access Journals (Sweden)

    Chiara De Luca

    2010-01-01

    Full Text Available Skin surface lipid (SSL film is a mixture of sebum and keratinocyte membrane lipids, protecting skin from environment. Its composition is unique for the high percentage of long chain fatty acids, and of the polyterpenoid squalene, absent in other human tissues, and in non-human Primates sebum. Here, the still incomplete body of information on SSL as mediators of external chemical, physical, and microbial signals and stressors is revised, focusing on the central event of the continuous oxidative modification induced by the metabolic activity of residential and pathological microbial flora, natural or iatrogenic UV irradiation, exposure to chemicals and cosmetics. Once alpha-tocopherol and ubiquinol-10 antioxidant defences of SSL are overcome, oxidation of squalene and cholesterol gives rise to reactive by-products penetrating deeper into skin layers, to mediate local defensive inflammatory, photo-protective, immune reactions or, at higher concentrations, inducing local but also systemic immune depression, ultimately implicating skin cancerogenesis. Qualitative modifications of SSL represent a pathogenetic sign of diagnostic value in dermatological disorders involving altered sebum production, like pytiriasis versicolor, acne, atopic or seborrheic dermatitis, as well as photo-aging. Achievements of nutriceutical interventions aimed at restoring normal SSL composition and homeostasis are discussed, as feasible therapeutic goals and major means of photo-protection.

  1. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

    Science.gov (United States)

    Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

    2015-09-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Inhibition of lipase and inflammatory mediators by Chlorella lipid extracts for antiacne treatment.

    Science.gov (United States)

    Sibi, G

    2015-01-01

    pathogen could be reduced by the inhibiting the production of ROS and inflammatory mediators TNF-α and exposes new frontiers on the antiacne activities of Chlorella lipid extracts.

  3. Inhibition of lipase and inflammatory mediators by Chlorella lipid extracts for antiacne treatment

    Directory of Open Access Journals (Sweden)

    G Sibi

    2015-01-01

    by the pathogen could be reduced by the inhibiting the production of ROS and inflammatory mediators TNF-α and exposes new frontiers on the antiacne activities of Chlorella lipid extracts.

  4. Oxalomalate, a competitive inhibitor of NADP+ -dependent isocitrate dehydrogenase, regulates lipid peroxidation-mediated apoptosis in U937 cells.

    Science.gov (United States)

    Yang, Eun Sun; Yang, Joon-Hyuck; Park, Ji Eun; Park, Jeen-Woo

    2005-01-01

    Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. Recently, we demonstrated that the control of cytosolic redox balance and the cellular defense against oxidative damage is one of the primary functions of cytosolic NADP+ -dependent isocitrate dehydrogenase (IDPc) through to supply NADPH for antioxidant systems. The protective role of IDPc against lipid peroxidation-mediated apoptosis in U937 cells was investigated in control and cells pre-treated with oxlalomalate, a competitive inhibitor of IDPc. Upon exposure to 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) to U937 cells, which induces lipid peroxidation in membranes, the susceptibility to apoptosis was higher in oxalomalate-treated cells as compared to control cells. The results suggest that IDPc plays an important protective role in apoptosis of U937 cells induced by lipid peroxidation-mediated oxidative stress.

  5. Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

    Science.gov (United States)

    Das, Anusuya; Barker, Daniel A; Wang, Tiffany; Lau, Cheryl M; Lin, Yong; Botchwey, Edward A

    2014-01-01

    In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid) (PLAGA) microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2) improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P) receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3) via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1) mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

  6. Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

    Directory of Open Access Journals (Sweden)

    Anusuya Das

    Full Text Available In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid (PLAGA microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2 improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3 via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1 mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

  7. Anti-angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid mediators.

    Science.gov (United States)

    Jin, Yiping; Arita, Makoto; Zhang, Qiang; Saban, Daniel R; Chauhan, Sunil K; Chiang, Nan; Serhan, Charles N; Dana, Reza

    2009-10-01

    Resolvins and lipoxins are lipid mediators generated from essential polyunsaturated fatty acids that are the first dual anti-inflammatory and pro-resolving signals identified in the resolution phase of inflammation. Here the authors investigated the potential of aspirin-triggered lipoxin (LX) A4 analog (ATLa), resolving (Rv) D1, and RvE1, in regulating angiogenesis in a murine model. ATLa and RvE1 receptor expression was tested in different corneal cell populations by RT-PCR. Corneal neovascularization (CNV) was induced by suture or micropellet (IL-1 beta, VEGF-A) placement. Mice were then treated with ATLa, RvD1, RvE1, or vehicle, subconjunctivally at 48-hour intervals. Infiltration of neutrophils and macrophages was quantified after immunofluorescence staining. The mRNA expression levels of inflammatory cytokines, VEGFs, and VEGFRs were analyzed by real-time PCR. CNV was evaluated intravitally and morphometrically. The receptors for LXA4, ALX/Fpr-rs-2 and for RvE1, ChemR23 were each expressed by epithelium, stromal keratocytes, and infiltrated CD11b(+) cells in corneas. Compared to the vehicle-treated eye, ATLa-, RvD1-, and RvE1-treated eyes had reduced numbers of infiltrating neutrophils and macrophages and reduced mRNA expression levels of TNF-alpha, IL-1 alpha, IL-1 beta, VEGF-A, VEGF-C, and VEGFR2. Animals treated with these mediators had significantly suppressed suture-induced or IL-1 beta-induced hemangiogenesis (HA) but not lymphangiogenesis. Interestingly, only the application of ATLa significantly suppressed VEGF-A-induced HA. ATLa, RvE1, and RvD1 all reduce inflammatory corneal HA by early regulation of resolution mechanisms in innate immune responses. In addition, ATLa directly inhibits VEGF-A-mediated angiogenesis and is the most potent inhibitor of NV among this new genus of dual anti-inflammatory and pro-resolving lipid mediators.

  8. Free radicals and lipid peroxidation mediated injury in burn trauma: the role of antioxidant therapy

    International Nuclear Information System (INIS)

    Horton, Jureta W.

    2003-01-01

    Burn trauma produces significant fluid shifts that, in turn, reduce cardiac output and tissue perfusion. Treatment approaches to major burn injury include administration of crystalloid solutions to correct hypovolemia and to restore peripheral perfusion. While this aggressive postburn volume replacement increases oxygen delivery to previously ischemic tissue, this restoration of oxygen delivery is thought to initiate a series of deleterious events that exacerbate ischemia-related tissue injury. While persistent hypoperfusion after burn trauma would produce cell death, volume resuscitation may exacerbate the tissue injury that occurred during low flow state. It is clear that after burn trauma, tissue adenosine triphosphate (ATP) levels gradually fall, and increased adenosine monophosphate (AMP) is converted to hypoxanthine, providing substrate for xanthine oxidase. These complicated reactions produce hydrogen peroxide and superoxide, clearly recognized deleterious free radicals. In addition to xanthine oxidase related free radical generation in burn trauma, adherent-activated neutrophils produce additional free radicals. Enhanced free radical production is paralleled by impaired antioxidant mechanisms; as indicated by burn-related decreases in superoxide dismutase, catalase, glutathione, alpha tocopherol, and ascorbic acid levels. Burn related upregulation of inducible nitric oxide synthase (iNOS) may produce peripheral vasodilatation, upregulate the transcription factor nuclear factor kappa B (NF-κB), and promote transcription and translation of numerous inflammatory cytokines. NO may also interact with the superoxide radical to yield peroxynitrite, a highly reactive mediator of tissue injury. Free radical mediated cell injury has been supported by postburn increases in systemic and tissue levels of lipid peroxidation products such as conjugated dienes, thiobarbituric acid reaction products, or malondialdehyde (MDA) levels. Antioxidant therapy in burn therapy

  9. Using AFM to probe the complexation of DNA with anionic lipids mediated by Ca(2+): the role of surface pressure.

    Science.gov (United States)

    Luque-Caballero, Germán; Martín-Molina, Alberto; Sánchez-Treviño, Alda Yadira; Rodríguez-Valverde, Miguel A; Cabrerizo-Vílchez, Miguel A; Maldonado-Valderrama, Julia

    2014-04-28

    Complexation of DNA with lipids is currently being developed as an alternative to classical vectors based on viruses. Most of the research to date focuses on cationic lipids owing to their spontaneous complexation with DNA. Nonetheless, recent investigations have revealed that cationic lipids induce a large number of adverse effects on DNA delivery. Precisely, the lower cytotoxicity of anionic lipids accounts for their use as a promising alternative. However, the complexation of DNA with anionic lipids (mediated by cations) is still in early stages and is not yet well understood. In order to explore the molecular mechanisms underlying the complexation of anionic lipids and DNA we proposed a combined methodology based on the surface pressure-area isotherms, Gibbs elasticity and Atomic Force Microscopy (AFM). These techniques allow elucidation of the role of the surface pressure in the complexation and visualization of the interfacial aggregates for the first time. We demonstrate that the DNA complexes with negatively charged model monolayers (DPPC/DPPS 4 : 1) only in the presence of Ca(2+), but is expelled at very high surface pressures. Also, according to the Gibbs elasticity plot, the complexation of lipids and DNA implies a whole fluidisation of the monolayer and a completely different phase transition map in the presence of DNA and Ca(2+). AFM imaging allows identification for the first time of specific morphologies associated with different packing densities. At low surface coverage, a branched net like structure is observed whereas at high surface pressure fibers formed of interfacial aggregates appear. In summary, Ca(2+) mediates the interaction between DNA and negatively charged lipids and also the conformation of the ternary system depends on the surface pressure. Such observations are important new generic features of the interaction between DNA and anionic lipids.

  10. Maresin 1, a Proresolving Lipid Mediator, Mitigates Carbon Tetrachloride-Induced Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Ruidong Li

    2016-01-01

    Full Text Available Maresin 1 (MaR 1 was recently reported to have protective properties in several different animal models of acute inflammation by inhibiting inflammatory response. However, its function in acute liver injury is still unknown. To address this question, we induced liver injury in BALB/c mice with intraperitoneal injection of carbon tetrachloride with or without treatment of MaR 1. Our data showed that MaR 1 attenuated hepatic injury, oxidative stress, and lipid peroxidation induced by carbon tetrachloride, as evidenced by increased thiobarbituric acid reactive substances and reactive oxygen species levels were inhibited by treatment of MaR 1. Furthermore, MaR 1 increased activities of antioxidative mediators in carbon tetrachloride-treated mice liver. MaR 1 decreased indices of inflammatory mediators such as tumor necrosis factor-α, interleukin-6, interleukin-1β, monocyte chemotactic protein 1, myeloperoxidase, cyclooxygenase-2, and inducible nitric oxide synthase. Administration of MaR 1 inhibited activation of nuclear factor kappa B (NF-κb and mitogen-activated protein kinases (MAPKs in the liver of CCl4 treated mice. In conclusion, these results suggested the antioxidative, anti-inflammatory properties of MaR 1 in CCl4 induced liver injury. The possible mechanism is partly implicated in its abilities to inhibit ROS generation and activation of NF-κb and MAPK pathway.

  11. Bioactive substances

    Digital Repository Service at National Institute of Oceanography (India)

    Wahidullah, S.

    Chemistry related to certain bioactive molecules, from Indian Ocean Region, developed into drugs or which served as models for the synthesis of more effective bioactive substances or in use in fundamental studies of physiological and biochemical...

  12. Lipid raft-associated β-adducin is required for PSGL-1-mediated neutrophil rolling on P-selectin.

    Science.gov (United States)

    Xu, Tingshuang; Liu, Wenai; Yang, Chen; Ba, Xueqing; Wang, Xiaoguang; Jiang, Yong; Zeng, Xianlu

    2015-02-01

    Lipid rafts, a liquid-ordered plasma membrane microdomain, are related to cell-surface receptor function. PSGL-1, a major surface receptor protein for leukocyte, also acts as a signaling receptor in leukocyte rolling. To investigate the role of lipid raft in PSGL-1 signaling in human neutrophils, we quantitatively analyzed lipid raft proteome of human promyelocytic leukemia cell line HL-60 cells and identified a lipid raft-associated protein β-adducin. PSGL-1 ligation induced dissociation of the raft-associated protein β-adducin from lipid rafts and actin, as well as phosphorylation of β-adducin, indicating a transient uncoupling of lipid rafts from the actin cytoskeleton. Knockdown of β-adducin greatly attenuated HL-60 cells rolling on P-selectin. We also showed that Src kinase is crucial for PSGL-1 ligation-induced β-adducin phosphorylation and relocation. Taken together, these results show that β-adducin is a pivotal lipid raft-associated protein in PSGL-1-mediated neutrophil rolling on P-selectin. © Society for Leukocyte Biology.

  13. Polychlorinated biphenyls exposure-induced insulin resistance is mediated by lipid droplet enlargement through Fsp27.

    Science.gov (United States)

    Kim, Hye Young; Kwon, Woo Young; Kim, Yeon A; Oh, Yoo Jin; Yoo, Seung Hee; Lee, Mi Hwa; Bae, Ju Yong; Kim, Jong-Min; Yoo, Young Hyun

    2017-06-01

    Although epidemiological and experimental studies demonstrated that polychlorinated biphenyls (PCBs) lead to insulin resistance, the mechanism underlying PCBs-induced insulin resistance has remained unsolved. In this study, we examined in vitro and in vivo effects of PCB-118 (dioxin-like PCB) and PCB-138 (non-dioxin-like PCB) on adipocyte differentiation, lipid droplet growth, and insulin action. 3T3-L1 adipocytes were incubated with PCB-118 or PCB-138 during adipocyte differentiation. For in vivo studies, C57BL/6 mice were administered PCB-118 or PCB-138 (37.5 mg/kg) by intraperitoneal injection and we examined adiposity and whole-body insulin action. PCB-118 and PCB-138 significantly promoted adipocyte differentiation and increased the lipid droplet (LD) size in 3T3-L1 adipocytes. In mice, both PCBs increased adipose mass and adipocyte size. Furthermore, both PCBs induced insulin resistance in vitro and in vivo. Expression of fat-specific protein 27 (Fsp27), which is localized to LD contact sites, was increased in PCB-treated 3T3-L1 adipocytes and mice. Depletion of Fsp27 by siRNA resulted in the inhibition of LD enlargement and attenuation of insulin resistance in PCB-treated 3T3-L1 adipocytes. An anti-diabetic drug, metformin, attenuated insulin resistance in PCB-treated 3T3-L1 adipocytes through the reduced expression of Fsp27 protein and LD size. This study suggests that PCB exposure-induced insulin resistance is mediated by LD enlargement through Fsp27.

  14. Ex Vivo Antioxidant Activity of Selected Medicinal Plants against Fenton Reaction-Mediated Oxidation of Biological Lipid Substrates

    Directory of Open Access Journals (Sweden)

    Namratha Pai Kotebagilu

    2015-01-01

    Full Text Available Free radical-mediated oxidation is often linked to various degenerative diseases. Biological substrates with lipids as major components are susceptible to oxygen-derived lipid peroxidation due to their composition. Lipid peroxide products act as biomarkers in evaluating the antioxidant potential of various plants and functional foods. The study focused on evaluation of the antioxidant potential of two extracts (methanol and 80% methanol of four medicinal plants, Andrographis paniculata, Costus speciosus, Canthium parviflorum, and Abrus precatorius, against Fenton reaction-mediated oxidation of three biological lipid substrates; cholesterol, low-density lipoprotein, and brain homogenate. The antioxidant activity of the extracts was measured by thiobarbituric acid reactive substances method. Also, the correlation between the polyphenol, flavonoid content, and the antioxidant activity in biological substrates was analyzed. Results indicated highest antioxidant potential by 80% methanol extract of Canthium parviflorum (97.55%, methanol extract of Andrographis paniculata (72.15%, and methanol extract of Canthium parviflorum (49.55% in cholesterol, low-density lipoprotein, and brain, respectively. The polyphenol and flavonoid contents of methanol extract of Andrographis paniculata in cholesterol (r=0.816 and low-density lipoprotein (r=0.948 and Costus speciosus in brain (r=0.977, polyphenols, and r=0.949, flavonoids correlated well with the antioxidant activity. The findings prove the antioxidant potential of the selected medicinal plants against Fenton reaction in biological lipid substrates.

  15. Oleic acid exposure of cultured endothelial cells alters lipid mediator production

    Science.gov (United States)

    Diesel, biodiesel, and other combustion sources contain free fatty acid (FFA) components capable of entering the body through particulate inhalation. FFA can also be endogenously released into circulation in response to stress. When in circulation, bioactive FFA may interact with...

  16. Effects of a combination of plant bioactive lipid compounds and biotin compared with monensin on body condition, energy metabolism and milk performance in transition dairy cows

    Science.gov (United States)

    Hausmann, Janis; Deiner, Carolin; Patra, Amlan K.; Immig, Irmgard; Starke, Alexander

    2018-01-01

    The aim of this study was to test whether a combination of plant bioactive lipid compounds (also termed ‘essential oils’) and biotin (PBLC+B) could decrease the mobilization of body reserves and ketosis incidence in postpartum dairy cows. We compared non-supplemented control (CON) cows with cows receiving monensin (MON) as a controlled-release capsule at d -21, and with cows receiving PBLC+B from day (d) -21 before calving until calving (Phase 1) and further until d 37 after calving (Phase 2), followed by PBLC+B discontinuation from d 38 to d 58 (Phase 3). The PBLC+B cows had higher body weight and higher back fat thickness than CON cows and lesser body weight change than MON and CON cows in Phase 3. Body condition score was not different among groups. Milk protein concentration tended to be higher on the first herd test day in PBLC+B vs. CON cows. Milk fat concentration tended to be highest in PBLC+B cows throughout Phases 2 and 3, with significantly higher values in PBLC+B vs. MON cows on the second herd test day. Yields of energy-corrected milk were higher in PBLC+B vs. CON and MON cows in Phase 2 and higher in PBLC+B and MON cows vs. CON cows in Phase 3. The incidence of subclinical ketosis was 83%, 61% and 50% in CON, PBLC+B and MON cows, respectively, with lower mean β-hydroxybutyrate values in MON than in PBLC+B cows in Phase 1 prepartum. The serum triglyceride concentration was higher in PBLC+B vs. CON cows on d 37. No differences were observed in serum glucose, urea, non-esterified fatty acids, cholesterol and bilirubin concentrations. Aspartate transaminase and γ-glutamyltranspeptidase but not glutamate dehydrogenase activities tended to be highest in MON and lowest in PBLC+B in Phase 2. We conclude that PBLC+B prevent body weight loss after parturition and are associated with similar ketosis incidence and partly higher yields of energy-corrected milk compared to MON supplementation of dairy cows. PMID:29584764

  17. Central mechanisms mediating the hypophagic effects of oleoylethanolamide and N-acylphosphatidylethanolamines: different lipid signals?

    Directory of Open Access Journals (Sweden)

    Adele eRomano

    2015-06-01

    Full Text Available The spread of ‘obesity epidemic’ and the poor efficacy of many anti-obesity therapies in the long-term highlight the need to develop novel efficacious therapy. This necessity stimulates a large research effort to find novel mechanisms controlling feeding and energy balance. Among these mechanisms a great deal of attention has been attracted by a family of phospholipid-derived signaling molecules that play an important role in the regulation of food-intake. They include N-acylethanolamines (NAEs and N-acylphosphatidylethanolamines (NAPEs. NAPEs have been considered for a long time simply as phospholipid precursors of the lipid mediator NAEs, but increasing body of evidence suggest a role in many physiological processes including the regulation of feeding behavior. Several observations demonstrated that among NAEs, oleoylethanolamide (OEA acts as a satiety signal, which is generated in the intestine, upon the ingestion of fat, and signals to the central nervous system. At this level different neuronal pathways, including oxytocinergic, noradrenergic, and histaminergic neurons, seem to mediate its hypophagic action. Similarly to NAEs, NAPEs (with particular reference to the N16:0 species levels were shown to be regulated by the fed state and this finding was initially interpreted as fluctuations of NAE precursors. However, the observation that exogenously administered NAPEs are able to inhibit food intake, not only in normal rats and mice but also in mice lacking the enzyme that converts NAPEs into NAEs, supported the hypothesis of a role of NAPE in the regulation of feeding behavior. Indirect observations suggest that the hypophagic action of NAPEs might involve central mechanisms, although the molecular target remains unknown. The present paper reviews the role that OEA and NAPEs play in the mechanisms that control food intake, further supporting this group of phospholipids as optimal candidate for the development of novel anti

  18. Pseudomonas aeruginosa sabotages the generation of host proresolving lipid mediators

    Energy Technology Data Exchange (ETDEWEB)

    Flitter, Becca A.; Hvorecny, Kelli L.; Ono, Emiko; Eddens, Taylor; Yang, Jun; Kwak, Daniel H.; Bahl, Christopher D.; Hampton, Thomas H.; Morisseau, Christophe; Hammock, Bruce D.; Liu, Xinyu; Lee, Janet S.; Kolls, Jay K.; Levy, Bruce D.; Madden, Dean R.; Bomberger, Jennifer M.

    2016-12-15

    Recurrent Pseudomonas aeruginosa infections coupled with robust, damaging neutrophilic inflammation characterize the chronic lung disease cystic fibrosis (CF). The proresolving lipid mediator, 15-epi lipoxin A4 (15-epi LXA4), plays a critical role in limiting neutrophil activation and tissue inflammation, thus promoting the return to tissue homeostasis. Here, we show that a secreted P. aeruginosa epoxide hydrolase, cystic fibrosis transmembrane conductance regulator inhibitory factor (Cif), can disrupt 15-epi LXA4 transcellular biosynthesis and function. In the airway, 15-epi LXA4 production is stimulated by the epithelial-derived eicosanoid 14,15-epoxyeicosatrienoic acid (14,15-EET). Cif sabotages the production of 15-epi LXA4 by rapidly hydrolyzing 14,15-EET into its cognate diol, eliminating a proresolving signal that potently suppresses IL-8–driven neutrophil transepithelial migration in vitro. Retrospective analyses of samples from patients with CF supported the translational relevance of these preclinical findings. Elevated levels of Cif in bronchoalveolar lavage fluid were correlated with lower levels of 15-epi LXA4, increased IL-8 concentrations, and impaired lung function. Together, these findings provide structural, biochemical, and immunological evidence that the bacterial epoxide hydrolase Cif disrupts resolution pathways during bacterial lung infections. The data also suggest that Cif contributes to sustained pulmonary inflammation and associated loss of lung function in patients with CF.

  19. Solid lipid nanoparticles mediate non-viral delivery of plasmid DNA to dendritic cells

    Science.gov (United States)

    Penumarthi, Alekhya; Parashar, Deepti; Abraham, Amanda N.; Dekiwadia, Chaitali; Macreadie, Ian; Shukla, Ravi; Smooker, Peter M.

    2017-06-01

    There is an increasing demand for novel DNA vaccine delivery systems, mainly for the non-viral type as they are considered relatively safe. Therefore, solid lipid nanoparticles (SLNs) were investigated for their suitability as a non-viral DNA vaccine delivery system. SLNs were synthesised by a modified solvent-emulsification method in order to study their potential to conjugate with plasmid DNA and deliver them in vitro to dendritic cells using eGFP as the reporter plasmid. The DNA-SLN complexes were characterised by electron microscopy, gel retardation assays and dynamic light scattering. The cytotoxicity assay data supported their biocompatibility and was used to estimate safe threshold concentration resulting in high transfection rate. The transfection efficiency of these complexes in a dendritic cell line was shown to increase significantly compared to plasmid alone, and was comparable to that mediated by lipofectamine. Transmission electron microscopy studies delineated the pathway of cellular uptake. Endosomal escape was observed supporting the mechanism of transfection.

  20. Kinetics of lipid-nanoparticle-mediated intracellular mRNA delivery and function

    Science.gov (United States)

    Zhdanov, Vladimir P.

    2017-10-01

    mRNA delivery into cells forms the basis for one of the new and promising ways to treat various diseases. Among suitable carriers, lipid nanoparticles (LNPs) with a size of about 100 nm are now often employed. Despite high current interest in this area, the understanding of the basic details of LNP-mediated mRNA delivery and function is limited. To clarify the kinetics of mRNA release from LNPs, the author uses three generic models implying (i) exponential, (ii) diffusion-controlled, and (iii) detachment-controlled kinetic regimes, respectively. Despite the distinct differences in these kinetics, the associated transient kinetics of mRNA translation to the corresponding protein and its degradation are shown to be not too sensitive to the details of the mRNA delivery by LNPs (or other nanocarriers). In addition, the author illustrates how this protein may temporarily influence the expression of one gene or a few equivalent genes. The analysis includes positive or negative regulation of the gene transcription via the attachment of the protein without or with positive or negative feedback in the gene expression. Stable, bistable, and oscillatory schemes have been scrutinized in this context.

  1. Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4

    International Nuclear Information System (INIS)

    Song, Jun; Ren, Pingping; Zhang, Lin; Wang, Xing Li; Chen, Li; Shen, Ying H.

    2010-01-01

    Objective: The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Strategies to reduce lipid accumulation in macrophages may have therapeutic potential for preventing and treating atherosclerosis and cardiovascular complications. The antidiabetic drug metformin has been reported to reduce lipid accumulation in adipocytes. In this study, we examined the effects of metformin on lipid accumulation in macrophages and investigated the mechanisms involved. Methods and results: We observed that metformin significantly reduced palmitic acid (PA)-induced intracellular lipid accumulation in macrophages. Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4) which was involved in PA-induced lipid accumulation. Quantitative real-time PCR showed that metformin regulates FABP4 expression at the transcriptional level. We identified forkhead transcription factor FOXO1 as a positive regulator of FABP4 expression. Inhibiting FOXO1 expression with FOXO1 siRNA significantly reduced basal and PA-induced FABP4 expression. Overexpression of wild-type FOXO1 and constitutively active FOXO1 significantly increased FABP4 expression, whereas dominant negative FOXO1 dramatically decreased FABP4 expression. Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity. Conclusions: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription. Thus, metformin may have a protective effect against lipid accumulation in macrophages and may serve as a therapeutic agent for preventing and treating atherosclerosis in metabolic syndrome.

  2. Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jun [Qilu Hospital, Shandong University, Jinan, Shandong (China); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Ren, Pingping; Zhang, Lin [Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Wang, Xing Li [Qilu Hospital, Shandong University, Jinan, Shandong (China); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Chen, Li [Qilu Hospital, Shandong University, Jinan, Shandong (China); Shen, Ying H., E-mail: hyshen@bcm.edu [Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States)

    2010-02-26

    Objective: The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Strategies to reduce lipid accumulation in macrophages may have therapeutic potential for preventing and treating atherosclerosis and cardiovascular complications. The antidiabetic drug metformin has been reported to reduce lipid accumulation in adipocytes. In this study, we examined the effects of metformin on lipid accumulation in macrophages and investigated the mechanisms involved. Methods and results: We observed that metformin significantly reduced palmitic acid (PA)-induced intracellular lipid accumulation in macrophages. Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4) which was involved in PA-induced lipid accumulation. Quantitative real-time PCR showed that metformin regulates FABP4 expression at the transcriptional level. We identified forkhead transcription factor FOXO1 as a positive regulator of FABP4 expression. Inhibiting FOXO1 expression with FOXO1 siRNA significantly reduced basal and PA-induced FABP4 expression. Overexpression of wild-type FOXO1 and constitutively active FOXO1 significantly increased FABP4 expression, whereas dominant negative FOXO1 dramatically decreased FABP4 expression. Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity. Conclusions: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription. Thus, metformin may have a protective effect against lipid accumulation in macrophages and may serve as a therapeutic agent for preventing and treating atherosclerosis in metabolic syndrome.

  3. Nanostructured hydroxyapatite surfaces-mediated adsorption alters recognition of BMP receptor IA and bioactivity of bone morphogenetic protein-2.

    Science.gov (United States)

    Huang, Baolin; Yuan, Yuan; Ding, Sai; Li, Jianbo; Ren, Jie; Feng, Bo; Li, Tong; Gu, Yuantong; Liu, Changsheng

    2015-11-01

    Highly efficient loading of bone morphogenetic protein-2 (BMP-2) onto carriers with desirable performance is still a major challenge in the field of bone regeneration. Till now, the nanoscaled surface-induced changes of the structure and bioactivity of BMP-2 remains poorly understood. Here, the effect of nanoscaled surface on the adsorption and bioactivity of BMP-2 was investigated with a series of hydroxyapatite surfaces (HAPs): HAP crystal-coated surface (HAP), HAP crystal-coated polished surface (HAP-Pol), and sintered HAP crystal-coated surface (HAP-Sin). The adsorption dynamics of recombinant human BMP-2 (rhBMP-2) and the accessibility of the binding epitopes of adsorbed rhBMP-2 for BMP receptors (BMPRs) were examined by a quartz crystal microbalance with dissipation. Moreover, the bioactivity of adsorbed rhBMP-2 and the BMP-induced Smad signaling were investigated with C2C12 model cells. A noticeably high mass-uptake of rhBMP-2 and enhanced recognition of BMPR-IA to adsorbed rhBMP-2 were found on the HAP-Pol surface. For the rhBMP-2-adsorbed HAPs, both ALP activity and Smad signaling increased in the order of HAP-Sinuses of rhBMP-2 in clinical applications and arouse broad interests among researchers in the fields of nano-biotechnology, biomaterials and bone tissue engineering. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

    Science.gov (United States)

    Zhang, Xian; Zhang, Jian-Hua; Chen, Xu-Yang; Hu, Qing-Hua; Wang, Ming-Xing; Jin, Rui; Zhang, Qing-Yu; Wang, Wei; Wang, Rong; Kang, Lin-Lin; Li, Jin-Sheng; Li, Meng

    2015-01-01

    Abstract Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant

  5. Lipid-mediated glial cell line-derived neurotrophic factor gene transfer to cultured porcine ventral mesencephalic tissue

    DEFF Research Database (Denmark)

    Bauer, Matthias; Meyer, Morten; Brevig, Thomas

    2002-01-01

    Transplantation of dopaminergic ventral mesencephalic (VM) tissue into the basal ganglia of patients with Parkinson's disease (PD) shows at best moderate symptomatic relief in some of the treated cases. Experimental animal studies and clinical trials with allogenic and xenogenic pig-derived VM...... tissue grafts to PD patients indicate that one reason for the poor outcome of neural transplantation is the low survival and differentiation of grafted dopaminergic neurons. To improve dopaminergic cell survival through a gene-therapeutic approach we have established and report here results of lipid-mediated...... numbers of tyrosine hydroxylase-positive neurons in the cultured VM tissue. We conclude that lipid-mediated gene transfer employed on embryonic pig VM explant cultures is a safe and effective method to improve survival of dopaminergic neurons and may become a valuable tool to improve allo...

  6. Cell type-specific modulation of lipid mediator's formation in murine adipose tissue by omega-3 fatty acids

    Czech Academy of Sciences Publication Activity Database

    Kuda, Ondřej; Rombaldová, Martina; Janovská, Petra; Flachs, Pavel; Kopecký, Jan

    2016-01-01

    Roč. 469, č. 3 (2016), s. 731-736 ISSN 0006-291X R&D Projects: GA ČR(CZ) GP13-04449P; GA ČR(CZ) GA13-00871S; GA MŠk(CZ) LH14040 Institutional support: RVO:67985823 Keywords : adipose tissue macrophages * omega-3 PUFA * protectin D1 * lipid mediators * lipidomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.466, year: 2016

  7. Lipid Mediators Are Critical in Resolving Inflammation: A Review of the Emerging Roles of Eicosanoids in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Fernando H. G. Tessaro

    2015-01-01

    Full Text Available The biosynthesis pathway of eicosanoids derived from arachidonic acid, such as prostaglandins and leukotrienes, relates to the pathophysiology of diabetes mellitus (DM. A better understanding of how lipid mediators modulate the inflammatory process may help recognize key factors underlying the progression of diabetes complications. Our review presents recent knowledge about eicosanoid synthesis and signaling in DM-related complications, and discusses eicosanoid-related target therapeutics.

  8. Mechanistic evaluation of the transfection barriers involved in lipid-mediated gene delivery: Interplay between nanostructure and composition

    Science.gov (United States)

    Pozzi, D.; Marchini, C.; Cardarelli, F.; Salomone, F.; Coppola, S.; Montani, M.; Zabaleta, M. Elexpuru; Digman, M.A.; Gratton, E.; Colapicchioni, V.; Caracciolo, G.

    2014-01-01

    Here we present a quantitative mechanism-based investigation aimed at comparing the cell uptake, intracellular trafficking, endosomal escape and final fate of lipoplexes and lipid–protamine/deoxyribonucleic acid (DNA) (LPD) nanoparticles (NPs) in living Chinese hamster ovary (CHO) cells. As a model, two lipid formulations were used for comparison. The first formulation is made of the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the zwitterionic lipid dioleoylphosphocholine (DOPC), while the second mixture is made of the cationic 3β-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and the zwitterionic helper lipid dioleoylphosphatidylethanolamine (DOPE). Our findings indicate that lipoplexes are efficiently taken up through fluid-phase macropinocytosis, while a less efficient uptake of LPD NPs occurs through a combination of both macropinocytosis and clathrin-dependent pathways. Inside the cell, both lipoplexes and LPD NPs are actively transported towards the cell nucleus, as quantitatively addressed by spatio-temporal image correlation spectroscopy (STICS). For each lipid formulation, LPD NPs escape from endosomes more efficiently than lipoplexes. When cells were treated with DOTAP–DOPC-containing systems the majority of the DNA was trapped in the lysosome compartment, suggesting that extensive lysosomal degradation was the rate-limiting factors in DOTAP–DOPC-mediated transfection. On the other side, escape from endosomes is large for DC-Chol–DOPE-containing systems most likely due to DOPE and cholesterol-like molecules, which are able to destabilize the endosomal membrane. The lipid-dependent and structure-dependent enhancement of transfection activity suggests that DNA is delivered to the nucleus synergistically: the process requires both the membrane-fusogenic activity of the nanocarrier envelope and the employment of lipid species with intrinsic endosomal rupture ability. PMID:24296066

  9. Localization of the placental BCRP/ABCG2 transporter to lipid rafts: Role for cholesterol in mediating efflux activity.

    Science.gov (United States)

    Szilagyi, John T; Vetrano, Anna M; Laskin, Jeffrey D; Aleksunes, Lauren M

    2017-07-01

    The breast cancer resistance protein (BCRP/ABCG2) is an efflux transporter in the placental barrier. By transporting chemicals from the fetal to the maternal circulation, BCRP limits fetal exposure to a range of drugs, toxicants, and endobiotics such as bile acids and hormones. The purpose of the present studies was to 1) determine whether BCRP localizes to highly-ordered, cholesterol-rich lipid raft microdomains in placenta microvillous membranes, and 2) determine the impact of cholesterol on BCRP-mediated placental transport in vitro. BCRP expression was analyzed in lipid rafts isolated from placentas from healthy, term pregnancies and BeWo trophoblasts by density gradient ultracentrifugation. BeWo cells were also tested for their ability to efflux BCRP substrates after treatment with the cholesterol sequestrant methyl-β-cyclodextrin (MβCD, 5 mM, 1 h) or the cholesterol synthesis inhibitor pravastatin (200 μM, 48 h). BCRP was found to co-localize with lipid raft proteins in detergent-resistant, lipid raft-containing fractions from placental microvillous membranes and BeWo cells. Treatment of BeWo cells with MβCD redistributed BCRP protein into higher density non-lipid raft fractions. Repletion of the cells with cholesterol restored BCRP localization to lipid raft-containing fractions. Treatment of BeWo cells with MβCD or pravastatin increased cellular retention of two BCRP substrates, the fluorescent dye Hoechst 33342 and the mycotoxin zearalenone. Repletion with cholesterol restored BCRP transporter activity. Taken together, these data demonstrate that cholesterol may play a critical role in the post-translational regulation of BCRP in placental lipid rafts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Dissociation of Calmodulin-Target Peptide Complexes by the Lipid Mediator Sphingosylphosphorylcholine

    Science.gov (United States)

    Kovacs, Erika; Tóth, Judit; Vértessy, Beáta G.; Liliom, Károly

    2010-01-01

    Previously we have identified the lipid mediator sphingosylphosphorylcholine (SPC) as the first potentially endogenous inhibitor of the ubiquitous Ca2+ sensor calmodulin (CaM) (Kovacs, E., and Liliom, K. (2008) Biochem. J. 410, 427–437). Here we give mechanistic insight into CaM inhibition by SPC, based on fluorescence stopped-flow studies with the model CaM-binding domain melittin. We demonstrate that both the peptide and SPC micelles bind to CaM in a rapid and reversible manner with comparable affinities. Furthermore, we present kinetic evidence that both species compete for the same target site on CaM, and thus SPC can be considered as a competitive inhibitor of CaM-target peptide interactions. We also show that SPC disrupts the complex of CaM and the CaM-binding domain of ryanodine receptor type 1, inositol 1,4,5-trisphosphate receptor type 1, and the plasma membrane Ca2+ pump. By interfering with these interactions, thus inhibiting the negative feedback that CaM has on Ca2+ signaling, we hypothesize that SPC could lead to Ca2+ mobilization in vivo. Hence, we suggest that the action of the sphingolipid on CaM might explain the previously recognized phenomenon that SPC liberates Ca2+ from intracellular stores. Moreover, we demonstrate that unlike traditional synthetic CaM inhibitors, SPC disrupts the complex between not only the Ca2+-saturated but also the apo form of the protein and the target peptide, suggesting a completely novel regulation for target proteins that constitutively bind CaM, such as ryanodine receptors. PMID:19910470

  11. Glucose Stimulation of Transforming Growth Factor-β Bioactivity in Mesangial Cells Is Mediated by Thrombospondin-1

    Science.gov (United States)

    Poczatek, Maria H.; Hugo, Christian; Darley-Usmar, Victor; Murphy-Ullrich, Joanne E.

    2000-01-01

    Glucose is a key factor in the development of diabetic complications, including diabetic nephropathy. The development of diabetic glomerulosclerosis is dependent on the fibrogenic growth factor, transforming growth factor-β (TGF-β). Previously we showed that thrombospondin-1 (TSP-1) activates latent TGF-β both in vitro and in vivo. Activation occurs as the result of specific interactions of latent TGF-β with TSP-1, which potentially alter the conformation of latent TGF-β. As glucose also up-regulates TSP-1 expression, we hypothesized that the increased TGF-β bioactivity observed in rat and human mesangial cells cultured with high glucose concentrations is the result of latent TGF-β activation by autocrine TSP-1. Glucose-induced bioactivity of TGF-β in mesangial cell cultures was reduced to basal levels by peptides from two different sequences that antagonize activation of latent TGF-β by TSP, but not by the plasmin inhibitor, aprotinin. Furthermore, glucose-dependent stimulation of matrix protein synthesis was inhibited by these antagonist peptides. These studies demonstrate that glucose stimulation of TGF-β activity and the resultant matrix protein synthesis are dependent on the action of autocrine TSP-1 to convert latent TGF-β to its biologically active form. These data suggest that antagonists of TSP-dependent TGF-β activation may be the basis of novel therapeutic approaches for ameliorating diabetic renal fibrosis. PMID:11021838

  12. Are lipid rafts involved in ABC transporter-mediated drug resistance of tumor cells?

    NARCIS (Netherlands)

    Kok, Jan Willem; Klappe, Karin; Hummel, Ina; Kroesen, Bart-Jan; Sietsma, Hannie; Meszaros, Peter

    2008-01-01

    Since their discovery, lipid rafts have been implicated in several cellular functions, including protein transport in polarized cells and signal transduction. Also in multidrug resistance lipid rafts may be important with regard to the localization of ATP-binding cassette (ABC) transporters in these

  13. Atorvastatin reduces lipid accumulation in the liver by activating protein kinase A-mediated phosphorylation of perilipin 5.

    Science.gov (United States)

    Gao, Xing; Nan, Yang; Zhao, Yuanlin; Yuan, Yuan; Ren, Bincheng; Sun, Chao; Cao, Kaiyu; Yu, Ming; Feng, Xuyang; Ye, Jing

    2017-12-01

    Statins have been proven to be effective in treating non-alcoholic fatty liver disease (NAFLD). Recently, it was reported that statins decreased the hepatic expression of perilipin 5 (Plin5), a lipid droplet (LD)-associated protein, which plays critical roles in regulating lipid accumulation and lipolysis in liver. However, the function and regulation mechanism of Plin5 have not yet been well-established in NAFLD treatment with statins. In this study, we observed that atorvastatin moderately reduced the expression of Plin5 in livers without changing the protein level of Plin5 in the hepatic LD fraction of mice fed with high-fat diet (HFD). Intriguingly, atorvastatin stimulated the PKA-mediated phosphorylation of Plin5 and reduced the triglyceride (TG) accumulation in hepatocytes with overexpression of wide type (Plin5-WT) compared to serine-155 mutant Plin5 (Plin5-S155A). Moreover, PKA-stimulated FA release of purified LDs carrying Plin5-WT but not Plin5-S155A. Glucagon, a PKA activator, stimulated the phosphorylation of Plin5-WT and inhibited its interaction with CGI-58. The results indicated that atorvastatin promoted lipolysis and reduced TG accumulation in the liver by increasing PKA-mediated phosphorylation of Plin5. This new mechanism of lipid-lowering effects of atorvastatin might provide a new strategy for NAFLD treatment. Copyright © 2017. Published by Elsevier B.V.

  14. New aspects of phloem-mediated long-distance lipid signaling in plants

    Directory of Open Access Journals (Sweden)

    Urs Florian Benning

    2012-03-01

    Full Text Available Plants are sessile and cannot move to appropriate hiding places or feeding grounds to escape adverse conditions. As a consequence, they evolved mechanisms to detect changes in their environment, communicate these to different organs, and adjust development accordingly. These adaptations include two long-distance transport systems which are essential in plants: the xylem and the phloem. The phloem serves as a major trafficking pathway for assimilates, viruses, RNA, plant hormones, metabolites, and proteins with functions ranging from synthesis to metabolism to signaling. The study of signaling compounds within the phloem is essential for our understanding of plant communication of environmental cues. Determining the nature of signals and the mechanisms by which they are communicated through the phloem will lead to a more complete understanding of plant development and plant responses to stress. In our analysis of Arabidopsis phloem exudates, we had identified several lipid-binding proteins as well as fatty acids and lipids. The latter are not typically expected in the aqueous environment of sieve elements. Hence, lipid transport in the phloem has been given little attention until now. Long-distance transport of hydrophobic compounds in an aqueous system is not without precedence in biological systems: a variety of lipids is found in human blood and are often bound to proteins. Some lipid-protein complexes are transported to other tissues for storage, use, modification, or degradation, others serve as messengers and modulate transcription factor activity. By simple analogy it raises the possibility that lipids and the respective lipid-binding proteins in the phloem serve similar functions in plants and play an important role in stress and developmental signaling. Here, we introduce the lipid-binding proteins and the lipids we found in the phloem and discuss the possibility that they may play an important role in developmental and stress signaling.

  15. Chiral chromatography-tandem mass spectrometry applied to the determination of pro-resolving lipid mediators.

    Science.gov (United States)

    Homann, Julia; Lehmann, Christoph; Kahnt, Astrid S; Steinhilber, Dieter; Parnham, Michael J; Geisslinger, Gerd; Ferreirós, Nerea

    2014-09-19

    Pro-resolving lipid mediators are a class of endogenously synthesized molecules derived from different fatty acids, such as arachidonic, docosahexaenoic or eicosapentaenoic acid, which are derived into four different product families: lipoxins, resolvins, maresins and protectins. For quantitation of these compounds, a sensitive, selective and robust liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantitation of lipoxin A4, 6-epi-lipoxin A4, lipoxin B4 and lipoxin A5, the D-series resolvins D1 and D2 as well as aspirin-triggered lipoxin A4 and resolvin D1, maresin and protectin and the pathway markers 17(S)-hydroxy-docosahexaenoic acid and 17(R)-hydroxy-docosahexaenoic acid in cell culture supernatants. For this purpose, a chiral column was connected in series with a reversed-phase column to achieve efficient analyte separation and high sensitivity. Sample pre-treatment included a fast and simple liquid-liquid extraction procedure. Limits of quantitation in the range of 0.1-0.5ng/mL cell culture media, absolute recoveries between 90 and 115%, intra- and interday precision of less than 13% and an accuracy of less than 11% were obtained. Stability of the samples after 60 days storage at -80°C, three freeze/thaw cycles and 4h at room temperature has been demonstrated for all analytes. Sample extracts can be stored at 7°C for 24h without degradation of the analytes. Deviations of less than 13% in the accuracy, evaluated in terms of relative error, were obtained. The suitability of the method has been demonstrated in cell culture supernatants of human polymorphonuclear leukocytes, stimulated with 15R-hydroxy-eicosatetraenoic acid and in cell culture media of human polymorphonuclear leukocytes co-incubated with human platelets. From all studied analytes, lipoxin A4 and 6-epi-lipoxin A4 were found in cell culture media under both incubation conditions, while 15-epi-lipoxin A4 was additionally detected in cell

  16. Keratin impact on PKCδ- and ASMase-mediated regulation of hepatocyte lipid raft size – implication for FasR-associated apoptosis

    Science.gov (United States)

    Gilbert, Stéphane; Loranger, Anne; Omary, M. Bishr

    2016-01-01

    ABSTRACT Keratins are epithelial cell intermediate filament (IF) proteins that are expressed as pairs in a cell-differentiation-regulated manner. Hepatocytes express the keratin 8 and 18 pair (denoted K8/K18) of IFs, and a loss of K8 or K18, as in K8-null mice, leads to degradation of the keratin partner. We have previously reported that a K8/K18 loss in hepatocytes leads to altered cell surface lipid raft distribution and more efficient Fas receptor (FasR, also known as TNFRSF6)-mediated apoptosis. We demonstrate here that the absence of K8 or transgenic expression of the K8 G62C mutant in mouse hepatocytes reduces lipid raft size. Mechanistically, we find that the lipid raft size is dependent on acid sphingomyelinase (ASMase, also known as SMPD1) enzyme activity, which is reduced in absence of K8/K18. Notably, the reduction of ASMase activity appears to be caused by a less efficient redistribution of surface membrane PKCδ toward lysosomes. Moreover, we delineate the lipid raft volume range that is required for an optimal FasR-mediated apoptosis. Hence, K8/K18-dependent PKCδ- and ASMase-mediated modulation of lipid raft size can explain the more prominent FasR-mediated signaling resulting from K8/K18 loss. The fine-tuning of ASMase-mediated regulation of lipid rafts might provide a therapeutic target for death-receptor-related liver diseases. PMID:27422101

  17. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure.

    OpenAIRE

    Felgner, P L; Gadek, T R; Holm, M; Roman, R; Chan, H W; Wenz, M; Northrop, J P; Ringold, G M; Danielsen, M

    1987-01-01

    A DNA-transfection protocol has been developed that makes use of a synthetic cationic lipid, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA). Small unilamellar liposomes containing DOTMA interact spontaneously with DNA to form lipid-DNA complexes with 100% entrapment of the DNA, DOTMA facilitates fusion of the complex with the plasma membrane of tissue culture cells, resulting in both uptake and expression of the DNA. The technique is simple, highly reproducible, and eff...

  18. Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes

    Directory of Open Access Journals (Sweden)

    Shiqi Zhang

    2018-03-01

    Full Text Available Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1, an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c and its target genes, diacylglycerol acyltransferase (DGAT 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL and CGI-58 for adipose triglyceride lipase (ATGL, thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α, interleukin 1 beta (IL-1β, and interleukin 6 (IL-6 induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

  19. Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes.

    Science.gov (United States)

    Zhang, Shiqi; Liu, Guowen; Xu, Chuang; Liu, Lei; Zhang, Qiang; Xu, Qiushi; Jia, Hongdou; Li, Xiaobing; Li, Xinwei

    2018-01-01

    Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

  20. Inhibition of Histone Deacetylases Permits Lipopolysaccharide-Mediated Secretion of Bioactive IL-1β via a Caspase-1-Independent Mechanism.

    Science.gov (United States)

    Stammler, Dominik; Eigenbrod, Tatjana; Menz, Sarah; Frick, Julia S; Sweet, Matthew J; Shakespear, Melanie R; Jantsch, Jonathan; Siegert, Isabel; Wölfle, Sabine; Langer, Julian D; Oehme, Ina; Schaefer, Liliana; Fischer, Andre; Knievel, Judith; Heeg, Klaus; Dalpke, Alexander H; Bode, Konrad A

    2015-12-01

    Histone deacetylase (HDAC) inhibitors (HDACi) are clinically approved anticancer drugs that have important immune-modulatory properties. We report the surprising finding that HDACi promote LPS-induced IL-1β processing and secretion in human and murine dendritic cells and murine macrophages. HDACi/LPS-induced IL-1β maturation and secretion kinetics differed completely from those observed upon inflammasome activation. Moreover, this pathway of IL-1β secretion was dependent on caspase-8 but was independent of the inflammasome components NACHT, LRR, and PYD domains-containing protein 3, apoptosis-associated speck-like protein containing a carboxyl-terminal caspase-recruitment domain, and caspase-1. Genetic studies excluded HDAC6 and HDAC10 as relevant HDAC targets in this pathway, whereas pharmacological inhibitor studies implicated the involvement of HDAC11. Treatment of mice with HDACi in a dextran sodium sulfate-induced colitis model resulted in a strong increase in intestinal IL-1β, confirming that this pathway is also operative in vivo. Thus, in addition to the conventional inflammasome-dependent IL-1β cleavage pathway, dendritic cells and macrophages are capable of generating, secreting, and processing bioactive IL-1β by a novel, caspase-8-dependent mechanism. Given the widespread interest in the therapeutic targeting of IL-1β, as well as the use of HDACi for anti-inflammatory applications, these findings have substantial clinical implications. Copyright © 2015 by The American Association of Immunologists, Inc.

  1. Drosophila lipophorin receptors mediate the uptake of neutral lipids in oocytes and imaginal disc cells by an endocytosis-independent mechanism.

    Directory of Open Access Journals (Sweden)

    Esmeralda Parra-Peralbo

    2011-02-01

    Full Text Available Lipids are constantly shuttled through the body to redistribute energy and metabolites between sites of absorption, storage, and catabolism in a complex homeostatic equilibrium. In Drosophila, lipids are transported through the hemolymph in the form of lipoprotein particles, known as lipophorins. The mechanisms by which cells interact with circulating lipophorins and acquire their lipidic cargo are poorly understood. We have found that lipophorin receptor 1 and 2 (lpr1 and lpr2, two partially redundant genes belonging to the Low Density Lipoprotein Receptor (LDLR family, are essential for the efficient uptake and accumulation of neutral lipids by oocytes and cells of the imaginal discs. Females lacking the lpr2 gene lay eggs with low lipid content and have reduced fertility, revealing a central role for lpr2 in mediating Drosophila vitellogenesis. lpr1 and lpr2 are transcribed into multiple isoforms. Interestingly, only a subset of these isoforms containing a particular LDLR type A module mediate neutral lipid uptake. Expression of these isoforms induces the extracellular stabilization of lipophorins. Furthermore, our data indicate that endocytosis of the lipophorin receptors is not required to mediate the uptake of neutral lipids. These findings suggest a model where lipophorin receptors promote the extracellular lipolysis of lipophorins. This model is reminiscent of the lipolytic processing of triglyceride-rich lipoproteins that occurs at the mammalian capillary endothelium, suggesting an ancient role for LDLR-like proteins in this process.

  2. Hypochlorous acid-mediated oxidation of lipid components and antioxidants present in low-density lipoproteins

    DEFF Research Database (Denmark)

    Pattison, David I; Hawkins, Clare Louise; Davies, Michael Jonathan

    2003-01-01

    Oxidation of low-density lipoproteins (LDL) is believed to contribute to the increased uptake of LDL by macrophages, which is an early event in atherosclerosis. Hypochlorous acid (HOCl) has been implicated as one of the major oxidants involved in these processes. In a previous study, the rates...... of reaction of HOCl with the reactive sites in proteins were investigated (Pattison, D. I., and Davies, M. J. (2001) Chem. Res. Toxicol. 14, 1453-1464). The work presented here expands on those studies to determine absolute second-order rate constants for the reactions of HOCl with various lipid components...... nitrogen- and carbon-centered radicals. Subsequent reactions of these species may induce oxidation of the LDL lipid component. In contrast, phosphoryl-choline reacted much more slowly (k Reaction of HOCl with 3-pentenoic acid was used as a model of lipid double bonds...

  3. Neutral lipids associated with haemozoin mediate efficient and rapid β-haematin formation at physiological pH, temperature and ionic composition

    Directory of Open Access Journals (Sweden)

    Ambele Melvin A

    2012-10-01

    Full Text Available Abstract Background The malaria parasite disposes of host-derived ferrihaem (iron(IIIprotoporphyrin IX, Fe(IIIPPIX by conversion to crystalline haemozoin in close association with neutral lipids. Lipids mediate synthetic haemozoin (β-haematin formation very efficiently. However, the effect on reaction rates of concentrations of lipid, Fe(IIIPPIX and physiologically relevant ions and biomolecules are unknown. Methods Lipid emulsions containing Fe(IIIPPIX were prepared in aqueous medium (pH 4.8, 37°C to mediate β-haematin formation. The reaction was quenched at various times and free Fe(IIIPPIX measured colorimetrically as a pyridine complex and the kinetics and yields analysed. Products were also characterized by FTIR, TEM and electron diffraction. Autofluorescence was also used to monitor β-haematin formation by confocal microscopy. Results At fixed Fe(IIIPPIX concentration, β-haematin yields remained constant with decreasing lipid concentration until a cut-off ratio was reached whereupon efficiency decreased dramatically. For the haemozoin-associated neutral lipid blend (NLB and monopalmitoylglycerol (MPG, this occurred below a lipid/Fe(IIIPPIX (L/H ratio of 0.54. Rate constants were found to increase with L/H ratio above the cut-off. At 16 μM MPG, Fe(IIIPPIX concentration could be raised until the L/H ratio reached the same ratio before a sudden decline in yield was observed. MPG-mediated β-haematin formation was relatively insensitive to biologically relevant cations (Na+, K+, Mg2+, Ca2+, or anions (H2PO4−, HCO3−, ATP, 2,3-diphosphoglycerate, glutathione. Confocal microscopy demonstrated β-haematin formation occurs in association with the lipid particles. Conclusions Kinetics of β-haematin formation have shown that haemozoin-associated neutral lipids alone are capable of mediating β-haematin formation at adequate rates under physiologically realistic conditions of ion concentrations to account for haemozoin formation.

  4. Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease.

    Directory of Open Access Journals (Sweden)

    Julio J Amaral

    Full Text Available Despite considerable efforts over the last decades, our understanding of leprosy pathogenesis remains limited. The complex interplay between pathogens and hosts has profound effects on host metabolism. To explore the metabolic perturbations associated with leprosy, we analyzed the serum metabolome of leprosy patients. Samples collected from lepromatous and tuberculoid patients before and immediately after the conclusion of multidrug therapy (MDT were subjected to high-throughput metabolic profiling. Our results show marked metabolic alterations during leprosy that subside at the conclusion of MDT. Pathways showing the highest modulation were related to polyunsaturated fatty acid (PUFA metabolism, with emphasis on anti-inflammatory, pro-resolving omega-3 fatty acids. These results were confirmed by eicosanoid measurements through enzyme-linked immunoassays. Corroborating the repertoire of metabolites altered in sera, metabonomic analysis of skin specimens revealed alterations in the levels of lipids derived from lipase activity, including PUFAs, suggesting a high lipid turnover in highly-infected lesions. Our data suggest that omega-6 and omega-3, PUFA-derived, pro-resolving lipid mediators contribute to reduced tissue damage irrespectively of pathogen burden during leprosy disease. Our results demonstrate the utility of a comprehensive metabonomic approach for identifying potential contributors to disease pathology that may facilitate the development of more targeted treatments for leprosy and other inflammatory diseases.

  5. Rutin as a Mediator of Lipid Metabolism and Cellular Signaling Pathways Interactions in Fibroblasts Altered by UVA and UVB Radiation

    Directory of Open Access Journals (Sweden)

    Agnieszka Gęgotek

    2017-01-01

    Full Text Available Background. Rutin is a natural nutraceutical that is a promising compound for the prevention of UV-induced metabolic changes in skin cells. The aim of this study was to examine the effects of rutin on redox and endocannabinoid systems, as well as proinflammatory and proapoptotic processes, in UV-irradiated fibroblasts. Methods. Fibroblasts exposed to UVA and UVB radiation were treated with rutin. The activities and levels of oxidants/antioxidants and endocannabinoid system components, as well as lipid, DNA, and protein oxidation products, and the proinflammatory and pro/antiapoptotic proteins expression were measured. Results. Rutin reduced UV-induced proinflammatory response and ROS generation and enhanced the activity/levels of antioxidants (SOD, GSH-Px, vitamin E, GSH, and Trx. Rutin also normalized UV-induced Nrf2 expression. Its biological activity prevented changes in the levels of the lipid mediators: MDA, 4-HNE, and endocannabinoids, as well as the endocannabinoid receptors CB1/2, VR1, and GPR55 expression. Furthermore, rutin prevented the protein modifications (tyrosine derivatives formation in particular and decreased the levels of the proapoptotic markers—caspase-3 and cytochrome c. Conclusion. Rutin prevents UV-induced inflammation and redox imbalance at protein and transcriptional level which favors lipid, protein, and DNA protection. In consequence rutin regulates endocannabinoid system and apoptotic balance.

  6. Determination of endogenous inflammation-related lipid mediators in ischemic stroke rats using background subtracting calibration curves by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Yang, Yang; Zhong, Qisheng; Mo, Canlong; Zhang, Hao; Zhou, Ting; Tan, Wen

    2017-11-01

    Accurate and reliable quantification of endogenous lipid mediators in complex biological samples is a daunting challenge. In this study, a robust and direct endogenous quantitative method using background subtracting calibration curves by liquid chromatography-tandem mass spectrometry was first developed for the determination of endogenous lipid mediators in ischemic stroke rats. Absolute quantification without surrogate matrix could be achieved by using background subtracting calibration curves, which were corrected and verified from standard curves constructed on original matrix. The recoveries of this method were in the range of 50.3-98.3%, the precision with the relative standard deviation was less than 13.8%, and the accuracy with the relative error was within ± 15.0%. In addition, background subtracting calibration curves were further verified by validation factors ranging from 90.3 to 110.9%. This validated method has been successfully applied to the analysis of seven endogenous inflammation-related lipid mediators in the brain tissues of ischemic stroke rats. The results indicated that prostaglandins as inflammatory factors and some lipid mediators with neuroprotective effects increased apparently (p endogenous compounds in the complex biological samples. Graphical abstract The analysis procedure of determining endogenous inflammation-related lipid mediators using BSCC by LC-MS/MS.

  7. PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism

    NARCIS (Netherlands)

    Diepen, van J.A.; Jansen, P.A.; Ballak, D.B.; Hijmans, A.; Hooiveld, G.J.E.J.; Rommelaere, S.; Kersten, A.H.; Stienstra, R.

    2014-01-01

    Background & Aims Peroxisome proliferator-activated receptor alpha (PPARa) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPARa target gene in liver, but its function in hepatic lipid metabolism is unknown.

  8. Alterations of plasma lipids in mice via adenoviral-mediated hepatic overexpression of human ABCA1

    NARCIS (Netherlands)

    Wellington, Cheryl L.; Brunham, Liam R.; Zhou, Steven; Singaraja, Roshni R.; Visscher, Henk; Gelfer, Allison; Ross, Colin; James, Erick; Liu, Guoqing; Huber, Mary T.; Yang, Yu-Zhou; Parks, Robin J.; Groen, Albert; Fruchart-Najib, Jamila; Hayden, Michael R.

    2003-01-01

    ATP binding cassette transporter A1 (ABCA1) is a widely expressed lipid transporter essential for the generation of HDL. ABCA1 is particularly abundant in the liver, suggesting that the liver may play a major role in HDL homeostasis. To determine how hepatic ABCA1 affects plasma HDL cholesterol

  9. Chitosan inhibits platelet-mediated clot retraction, increases platelet-derived growth factor release, and increases residence time and bioactivity of platelet-rich plasma in vivo.

    Science.gov (United States)

    Deprés-Tremblay, Gabrielle; Chevrier, Anik; Tran-Khanh, Nicolas; Nelea, Monica; Buschmann, Michael D

    2017-11-10

    Platelet-rich plasma (PRP) has been used to treat different orthopedic conditions, however, the clinical benefits of using PRP remain uncertain. Chitosan (CS)-PRP implants have been shown to improve meniscus, rotator cuff and cartilage repair in pre-clinical models. The purpose of this current study was to investigate in vitro and in vivo mechanisms of action of CS-PRP implants. Freeze-dried formulations containing 1% (w/v) CS (80% degree of deacetylation and number average molar mass 38 kDa), 1% (w/v) trehalose as a lyoprotectant and 42.2 mM calcium chloride as a clot activator were solubilized in PRP. Gravimetric measurements and molecular/cellular imaging studies revealed that clot retraction is inhibited in CS-PRP hybrid clots through physical coating of platelets, blood cells and fibrin strands by chitosan, which interferes with platelet aggregation and platelet-mediated clot retraction. Flow cytometry and ELISA assays revealed that platelets are activated and granules secreted in CS-PRP hybrid clots and that cumulative release of platelet-derived growth factor (PDGF-AB) and epidermal growth factor is higher from CS-PRP hybrid clots compared to PRP clots in vitro. Finally, CS-PRP implants resided for up to 6 weeks in a subcutaneous implantation model and induced cell recruitment and granulation tissue synthesis, confirming greater residency and bioactivity compared to PRP in vivo.

  10. Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid Mediators of Inflammation to Ameliorate the Deleterious Effects of Blast Overpressure on Eye and Brain Visual Processing Centers in Rats

    Science.gov (United States)

    2014-10-01

    acid ( DHA ; 22:6ω-3) Eicosapentaenoic acid (EPA; 20:5ω-3) Lipoxin A4 Resolvin E1 Protectin DX Resolvin D1 LOX LOX LOX Structures and Endogenous Source...1 AD_________________ Award Number: W81XWH-12-2-0082 TITLE: Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid...Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid Mediators 5a. CONTRACT NUMBER of Inflammation to Ameliorate the Deleterious Effects of

  11. Lipofection: A Highly Efficient, Lipid-Mediated DNA-Transfection Procedure

    Science.gov (United States)

    Felgner, Philip L.; Gadek, Thomas R.; Holm, Marilyn; Roman, Richard; Chan, Hardy W.; Wenz, Michael; Northrop, Jeffrey P.; Ringold, Gordon M.; Danielsen, Mark

    1987-11-01

    A DNA-transfection protocol has been developed that makes use of a synthetic cationic lipid, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA). Small unilamellar liposomes containing DOTMA interact spontaneously with DNA to form lipid-DNA complexes with 100% entrapment of the DNA. DOTMA facilitates fusion of the complex with the plasma membrane of tissue culture cells, resulting in both uptake and expression of the DNA. The technique is simple, highly reproducible, and effective for both transient and stable expression of transfected DNA. Depending upon the cell line, lipofection is from 5- to >100-fold more effective than either the calcium phosphate or the DEAE-dextran transfection technique.

  12. Diffusion mediated coagulation and fragmentation based study of domain formation in lipid bilayer membrane

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Laxminarsimha V., E-mail: laxman@iitk.ac.in [Mechanics and Applied Mathematics Group, Department of Mechanical Engineering, Indian Institute of Technology Kanpur, Kanpur 208016 (India); Roy, Subhradeep [Department of Biomedical Engineering and Mechanics (MC 0219), Virginia Tech, 495 Old Turner Street, Blacksburg, VA 24061 (United States); Das, Sovan Lal [Mechanics and Applied Mathematics Group, Department of Mechanical Engineering, Indian Institute of Technology Kanpur, Kanpur 208016 (India)

    2017-01-15

    We estimate the equilibrium size distribution of cholesterol rich micro-domains on a lipid bilayer by solving Smoluchowski equation for coagulation and fragmentation. Towards this aim, we first derive the coagulation kernels based on the diffusion behaviour of domains moving in a two dimensional membrane sheet, as this represents the reality better. We incorporate three different diffusion scenarios of domain diffusion into our coagulation kernel. Subsequently, we investigate the influence of the parameters in our model on the coagulation and fragmentation behaviour. The observed behaviours of the coagulation and fragmentation kernels are also manifested in the equilibrium domain size distribution and its first moment. Finally, considering the liquid domains diffusing in a supported lipid bilayer, we fit the equilibrium domain size distribution to a benchmark solution.

  13. Ferromagnetic filled carbon nanotubes and nanoparticles: synthesis and lipid-mediated delivery into human tumor cells

    International Nuclear Information System (INIS)

    Moench, I.; Meye, A.; Leonhardt, A.; Kraemer, K.; Kozhuharova, R.; Gemming, T.; Wirth, M.P.; Buechner, B.

    2005-01-01

    We describe the synthesis and the properties of Fe-filled multi-walled carbon nanotubes (MWNTs) and nanoparticles (NP) produced by chemical vapor deposition (CVD). We have employed ferrocene as a starting substance and oxidized Si-wafers as substrates. The magnetic properties and the interaction of the material with bladder cancer cells were determined. After the addition of NP suspensions to cultured cells, no adhesion of the nanoparticles/nanotubes (NT/NP) to the cell membrane and also no cellular uptake were observed. However, the preincubation of the (NT/NP) suspension with cationic lipid caused an efficient delivery of the lipid-nanostructure complexes into the cytoplasm within 2 h after adding to the culture medium

  14. Lipid Bilayer – mediated Regulation of Ion Channel Function by Amphiphilic Drugs

    DEFF Research Database (Denmark)

    Lundbæk, Jens August

    2008-01-01

    that are transforming it into a subject of quantitative science. It is described how the hydrophobic interactions between a membrane protein and the host lipid bilayer provide the basis for a mechanism, whereby protein function is regulated by the bilayer physical properties. The use of gramicidin channels as single-molecule......Drugs that at pico- to nanomolar concentration regulate ion channel function by high-affi nity binding to their cognate receptor often have a “ secondary pharmacology, ” in which the same molecule at low micromolar concentrations regulates a diversity of membrane proteins in an apparently...... nonspecifi c manner. It has long been suspected that this promiscuous regulation of membrane protein function could be due to changes in the physical properties of the host lipid bilayer, but the underlying mechanisms have been poorly understood. Given that pharmacological research often involves drug...

  15. Novel free-radical mediated lipid peroxidation biomarkers in newborn plasma.

    Science.gov (United States)

    Sánchez-Illana, Ángel; Thayyil, Sudhin; Montaldo, Paolo; Jenkins, Dorothea; Quintás, Guillermo; Oger, Camille; Galano, Jean-Marie; Vigor, Claire; Durand, Thierry; Vento, Máximo; Kuligowski, Julia

    2017-12-15

    Oxidative stress derived from perinatal asphyxia appears to be closely linked to neonatal brain damage and lipid peroxidation biomarkers have shown to provide predictive power of oxidative stress related pathologies in situations of hypoxia and reoxygenation in the newborn. The objective of this work was to develop and validate of a comprehensive liquid chromatography tandem mass spectrometry approach for the quantitative profiling of 28 isoprostanoids in newborn plasma samples covering a broad range of lipid peroxidation product classes. The method was developed taking into account the specific requirements for its use in neonatology (i.e. limited sample volumes, straightforward sample processing and high analytical throughput). The method was validated following stringent FDA guidelines and was then applied to the analysis of 150 plasma samples collected from newborns. Information obtained from the quantitative analysis of isoprostanoids was critically compared to that provided by a previously developed approach aiming at the semi-quantitative detection of total parameters of fatty acid derived lipid peroxidation biomarkers. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Protection against lethal Marburg virus infection mediated by lipid encapsulated small interfering RNA.

    Science.gov (United States)

    Ursic-Bedoya, Raul; Mire, Chad E; Robbins, Marjorie; Geisbert, Joan B; Judge, Adam; MacLachlan, Ian; Geisbert, Thomas W

    2014-02-15

    Marburg virus (MARV) infection causes severe morbidity and mortality in humans and nonhuman primates. Currently, there are no licensed therapeutics available for treating MARV infection. Here, we present the in vitro development and in vivo evaluation of lipid-encapsulated small interfering RNA (siRNA) as a potential therapeutic for the treatment of MARV infection. The activity of anti-MARV siRNAs was assessed using dual luciferase reporter assays followed by in vitro testing against live virus. Lead candidates were tested in lethal guinea pig models of 3 different MARV strains (Angola, Ci67, Ravn). Treatment resulted in 60%-100% survival of guinea pigs infected with MARV. Although treatment with siRNA targeting other MARV messenger RNA (mRNA) had a beneficial effect, targeting the MARV NP mRNA resulted in the highest survival rates. NP-718m siRNA in lipid nanoparticles provided 100% protection against MARV strains Angola and Ci67, and 60% against Ravn. A cocktail containing NP-718m and NP-143m provided 100% protection against MARV Ravn. These data show protective efficacy against the most pathogenic Angola strain of MARV. Further development of the lipid nanoparticle technology has the potential to yield effective treatments for MARV infection.

  17. Structure relationship of cationic lipids on gene transfection mediated by cationic liposomes.

    Science.gov (United States)

    Paecharoenchai, Orapan; Niyomtham, Nattisa; Apirakaramwong, Auayporn; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Yingyongnarongkul, Boon-ek; Opanasopit, Praneet

    2012-12-01

    The aim of this study was to investigate the transfection efficiency of cationic liposomes formulated with phosphatidylcholine (PC) and novel synthesized diethanolamine-based cationic lipids at a molar ratio of 5:1 in comparison with Lipofectamine™ 2000. Factors affecting transfection efficiency and cell viability, including the chemical structure of the cationic lipids, such as different amine head group (diamine and polyamine; and non-spermine and spermine) and acyl chain lengths (C14, C16, and C18) and the weight ratio of liposomes to DNA were evaluated on a human cervical carcinoma cell line (HeLa cells) using the pDNA encoding green fluorescent protein (pEGFP-C2). Characterizations of these lipoplexes in terms of size and charge measurement and agarose gel electrophoresis were performed. The results from this study revealed that almost no transfection was observed in the liposome formulations composed of cationic lipids with a non-spermine head group. In addition, the transfection efficiency of these cationic liposomes was in the following order: spermine-C14 > spermine-C16 > spermine-C18. The highest transfection efficiency was observed in the formulation of spermine-C14 liposomes at a weight ratio of 25; furthermore, this formulation was safe for use in vitro. In conclusion, cationic liposomes containing spermine head groups demonstrated promising potential as gene carriers.

  18. Biosynthesis, Characterization, and Bioactivities Evaluation of Silver and Gold Nanoparticles Mediated by the Roots of Chinese Herbal Angelica pubescens Maxim

    Science.gov (United States)

    Markus, Josua; Wang, Dandan; Kim, Yeon-Ju; Ahn, Sungeun; Mathiyalagan, Ramya; Wang, Chao; Yang, Deok Chun

    2017-01-01

    A facile synthesis and biological applications of silver (DH-AgNps) and gold nanoparticles (DH-AuNps) mediated by the aqueous extract of Angelicae Pubescentis Radix (Du Huo) are explored. Du Huo is a medicinal root belonging to Angelica pubescens Maxim which possesses anti-inflammatory, analgesic, and antioxidant properties. The absorption spectra of nanoparticles in varying root extract and metal ion concentration, pH, reaction temperatures, and time were recorded by ultraviolet-visible (UV-Vis) spectroscopy. The presence of DH-AgNps and DH-AuNps was confirmed from the surface plasmon resonance intensified at 414 and 540 nm, respectively. Field emission transmission electron micrograph (FE-TEM) analysis revealed the formation of quasi-spherical DH-AgNps and spherical icosahedral DH-AuNps. These novel DH-AgNps and DH-AuNps maintained an average crystallite size of 12.48 and 7.44 nm, respectively. The biosynthesized DH-AgNps and DH-AuNps exhibited antioxidant activity against 2,2-diphenyl-1-picrylhydrzyl (DPPH) radicals and the former exhibited antimicrobial activity against clinical pathogens including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella enterica. The expected presence of flavonoids, sesquiterpenes, and phenols on the nanoparticle surface were conjectured to grant protection against aggregation and free radical scavenging activity. DH-AgNps and DH-AuNps were further investigated for their cytotoxic properties in RAW264.7 macrophages for their potential application as drug carriers to sites of inflammation. In conclusion, this green synthesis is favorable for the advancement of plant mediated nano-carriers in drug delivery systems, cancer diagnostic, and medical imaging.

  19. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines

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    Edismauro Garcia Freitas Filho

    2016-01-01

    Full Text Available Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators.

  20. β-Amyloid promotes accumulation of lipid peroxides by inhibiting CD36-mediated clearance of oxidized lipoproteins

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    Khan Tayeba

    2004-11-01

    Full Text Available Abstract Background Recent studies suggest that hypercholesterolemia, an established risk factor for atherosclerosis, is also a risk factor for Alzheimer's disease. The myeloid scavenger receptor CD36 binds oxidized lipoproteins that accumulate with hypercholesterolemia and mediates their clearance from the circulation and peripheral tissues. Recently, we demonstrated that CD36 also binds fibrillar β-amyloid and initiates a signaling cascade that regulates microglial recruitment and activation. As increased lipoprotein oxidation and accumulation of lipid peroxidation products have been reported in Alzheimer's disease, we investigated whether β-amyloid altered oxidized lipoprotein clearance via CD36. Methods The availability of mice genetically deficient in class A (SRAI & II and class B (CD36 scavenger receptors has facilitated studies to discriminate their individual actions. Using primary microglia and macrophages, we assessed the impact of Aβ on: (a cholesterol ester accumulation by GC-MS and neutral lipid staining, (b binding, uptake and degradation of 125I-labeled oxidized lipoproteins via CD36, SR-A and CD36/SR-A-independent pathways, (c expression of SR-A and CD36. In addition, using mice with targeted deletions in essential kinases in the CD36-signaling cascade, we investigated whether Aβ-CD36 signaling altered metabolism of oxidized lipoproteins. Results In primary microglia and macrophages, Aβ inhibited binding, uptake and degradation of oxidized low density lipoprotein (oxLDL in a dose-dependent manner. While untreated cells accumulated abundant cholesterol ester in the presence of oxLDL, cells treated with Aβ were devoid of cholesterol ester. Pretreatment of cells with Aβ did not affect subsequent degradation of oxidized lipoproteins, indicating that lysosomal accumulation of Aβ did not disrupt this degradation pathway. Using mice with targeted deletions of the scavenger receptors, we demonstrated that Aβ inhibited oxidized

  1. Seaweed Bioactivity

    DEFF Research Database (Denmark)

    Zaharudin, Nazikussabah Binti

    . In conclusion, two brown seaweeds, Laminaria digitata and Undaria pinnatifida, inhibited α-amylase and α-glucosidase activities due to their content of several bioactive components with a potential use for future functional foods. Their effects on the postprandial insulin response and the in vitro findings...

  2. Prospects of fatty acid profile and bioactive composition from lipid seeds for the discrimination of apple varieties with the application of chemometrics

    Energy Technology Data Exchange (ETDEWEB)

    Arain, S.; Sherazzi, S. T. H.; Bhanger, M. I.; Memon, N.; Mahesar, S. A.; Rajput, M. T.

    2012-11-01

    The extracted oils from four apple seed varieties (Royal Gala, Red Delicious, Pyrus Malus and Golden Delicious) from Pakistan were investigated for their fatty acid profiles and lipid biactives by GC-MS. The oil contents in the seeds of the apple varieties ranged from 26.8-28.7%. The results revealed that linoleic acid (40.5-49.6%) was the main fatty acid in the Royal Gala, Red Delicious and Pyrus Malus seeds, and oleic acid (38.7-45.5%) was the main fatty acid in the Golden Delicious seeds. Palmitic acid (6.1-7.4%) and stearic acid (2.0-3.1%) were the dominant saturated fatty acids, besides the small amount of palmitoleic, heptadecanoic, linolenic, archidic, eicosanoic, and behenic acids. Sterols, tocopherols, hydrocarbons and some other minor components were also identified from the unsaponifiable lipid fraction. The variation among the results of both fatty acids and lipid bio actives for the four different varieties was assessed by principal component analysis, discriminant analysis and cluster analyses. The results conclude that both oil fractions could be applied as a useful tool to discriminate among the apple seed varieties. (Author) 42 refs.

  3. Interdependence of laminin-mediated clustering of lipid rafts and the dystrophin complex in astrocytes.

    Science.gov (United States)

    Noël, Geoffroy; Tham, Daniel Kai Long; Moukhles, Hakima

    2009-07-17

    Astrocyte endfeet surrounding blood vessels are active domains involved in water and potassium ion transport crucial to the maintenance of water and potassium ion homeostasis in brain. A growing body of evidence points to a role for dystroglycan and its interaction with perivascular laminin in the targeting of the dystrophin complex and the water-permeable channel, aquaporin 4 (AQP4), at astrocyte endfeet. However, the mechanisms underlying such compartmentalization remain poorly understood. In the present study we found that AQP4 resided in Triton X-100-insoluble fraction, whereas dystroglycan was recovered in the soluble fraction in astrocytes. Cholesterol depletion resulted in the translocation of a pool of AQP4 to the soluble fraction indicating that its distribution is indeed associated with cholesterol-rich membrane domains. Upon laminin treatment AQP4 and the dystrophin complex, including dystroglycan, reorganized into laminin-associated clusters enriched for the lipid raft markers GM1 and flotillin-1 but not caveolin-1. Reduced diffusion rates of GM1 in the laminin-induced clusters were indicative of the reorganization of raft components in these domains. In addition, both cholesterol depletion and dystroglycan silencing reduced the number and area of laminin-induced clusters of GM1, AQP4, and dystroglycan. These findings demonstrate the interdependence between laminin binding to dystroglycan and GM1-containing lipid raft reorganization and provide novel insight into the dystrophin complex regulation of AQP4 polarization in astrocytes.

  4. Microtubule-Mediated Inositol Lipid Signaling Plays Critical Roles in Regulation of Blebbing.

    Directory of Open Access Journals (Sweden)

    Tatsuroh Sugiyama

    Full Text Available Cells migrate by extending pseudopods such as lamellipodia and blebs. Although the signals leading to lamellipodia extension have been extensively investigated, those for bleb extension remain unclear. Here, we investigated signals for blebbing in Dictyostelium cells using a newly developed assay to induce blebbing. When cells were cut into two pieces with a microneedle, the anucleate fragments vigorously extended blebs. This assay enabled us to induce blebbing reproducibly, and analyses of knockout mutants and specific inhibitors identified candidate molecules that regulate blebbing. Blebs were also induced in anucleate fragments of leukocytes, indicating that this assay is generally applicable to animal cells. After cutting, microtubules in the anucleate fragments promptly depolymerized, followed by the extension of blebs. Furthermore, when intact cells were treated with a microtubule inhibitor, they frequently extended blebs. The depolymerization of microtubules induced the delocalization of inositol lipid phosphatidylinositol 3,4,5-trisphosphate from the cell membrane. PI3 kinase-null cells frequently extended blebs, whereas PTEN-null cells extended fewer blebs. From these observations, we propose a model in which microtubules play a critical role in bleb regulation via inositol lipid metabolism.

  5. TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology

    Science.gov (United States)

    Entwistle, Lewis J.; Khoury, Hania; Papoutsopoulou, Stamatia; Mahmood, Radma; Mansour, Nuha R.; Ching-Cheng Huang, Stanley; Pearce, Edward J.; Pedro S. de Carvalho, Luiz; Ley, Steven C.

    2016-01-01

    Persistent TH2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. Despite a good understanding of the cellular mechanisms involved in fibrogenesis, there are very few therapeutic options available, highlighting a significant medical need and gap in our understanding of the molecular mechanisms of TH2-mediated immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8; Cot) regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology following Schistosoma mansoni infection or S. mansoni egg injection. Elevated inflammation, TH2 cell responses and exacerbated fibrosis in Map3k8 –/–mice was observed in mice with myeloid cell-specific (LysM) deletion of Map3k8, but not CD4 cell-specific deletion of Map3k8, indicating that TPL-2 regulated myeloid cell function to limit TH2-mediated immunopathology. Transcriptional and metabolic assays of Map3k8 –/–M2 macrophages identified that TPL-2 was required for lipolysis, M2 macrophage activation and the expression of a variety of genes involved in immuno-regulatory and pro-fibrotic pathways. Taken together this study identified that TPL-2 regulated TH2-mediated inflammation by supporting lipolysis and M2 macrophage activation, preventing TH2 cell expansion and downstream immunopathology and fibrosis. PMID:27487182

  6. Long chain fatty acids and related pro-inflammatory, specialized pro-resolving lipid mediators and their intermediates in preterm human milk during the first month of lactation.

    Science.gov (United States)

    Robinson, D T; Palac, H L; Baillif, V; Van Goethem, E; Dubourdeau, M; Van Horn, L; Martin, C R

    2017-06-01

    This study aimed to measure longitudinal quantities of the long chain fatty acids, their biologically active terminal metabolites and related intermediates (also called oxylipins) in preterm human milk expressed during the first month of lactation. In a prospective cohort, breast milk was collected throughout the first month of lactation in 30 women who delivered preterm infants. Eighteen bioactive lipids and their intermediates were quantified via solid phase extraction and LC-MS/MS. Analysis by GC-FID quantified the fatty acid precursors. Arachidonic acid (ARA) and docosahexaenoic acid (DHA) milk concentrations significantly declined throughout the first month. Oxylipin concentrations did not change during lactation. Positive associations existed between ARA and thromboxane B2, eicosapentaenoic acid and 18-hydroxyeicosapentaenoic acid, and between DHA and PDX and 14- and 17-hydroxydocosahexaenoic acids. DHA concentrations were 1.5 times higher and 14-HDHA was 1.7 times higher in milk from women taking DHA supplements. This investigation showed conditionally essential fatty acids, ARA and DHA, decreased in preterm milk, suggesting a need to supplement their intake for the breast milk-fed preterm infant. Positive associations between parent fatty acids, bioactive lipids and intermediates, as well as sensitivity of milk to maternal fatty acid intake, support consideration of a comprehensive approach to providing fatty acids for preterm infants through both maternal and infant supplementation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology.

    Directory of Open Access Journals (Sweden)

    Mojgan Masoodi

    Full Text Available Ulcerative colitis (UC is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC.Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically.Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems.Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile.

  8. A lipid-mediated conformational switch modulates the thermosensing activity of DesK.

    Science.gov (United States)

    Inda, María Eugenia; Vandenbranden, Michel; Fernández, Ariel; de Mendoza, Diego; Ruysschaert, Jean-Marie; Cybulski, Larisa Estefanía

    2014-03-04

    The thermosensor DesK is a multipass transmembrane histidine-kinase that allows the bacterium Bacillus subtilis to adjust the levels of unsaturated fatty acids required to optimize membrane lipid fluidity. The cytoplasmic catalytic domain of DesK behaves like a kinase at low temperature and like a phosphatase at high temperature. Temperature sensing involves a built-in instability caused by a group of hydrophilic residues located near the N terminus of the first transmembrane (TM) segment. These residues are buried in the lipid phase at low temperature and partially "buoy" to the aqueous phase at higher temperature with the thinning of the membrane, promoting the required conformational change. Nevertheless, the core question remains poorly understood: How is the information sensed by the transmembrane region converted into a rearrangement in the cytoplasmic catalytic domain to control DesK activity? Here, we identify a "linker region" (KSRKERERLEEK) that connects the TM sensor domain with the cytoplasmic catalytic domain involved in signal transmission. The linker adopts two conformational states in response to temperature-dependent membrane thickness changes: (i) random coiled and bound to the phospholipid head groups at the water-membrane interface, promoting the phosphatase state or (ii) unbound and forming a continuous helix spanning a region from the membrane to the cytoplasm, promoting the kinase state. Our results uphold the view that the linker is endowed with a helix/random coil conformational duality that enables it to behave like a transmission switch, with helix disruption decreasing the kinase/phosphatase activity ratio, as required to modulate the DesK output response.

  9. Calcineurin signaling and membrane lipid homeostasis regulates iron mediated multidrug resistance mechanisms in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Saif Hameed

    2011-04-01

    Full Text Available We previously demonstrated that iron deprivation enhances drug susceptibility of Candida albicans by increasing membrane fluidity which correlated with the lower expression of ERG11 transcript and ergosterol levels. The iron restriction dependent membrane perturbations led to an increase in passive diffusion and drug susceptibility. The mechanisms underlying iron homeostasis and multidrug resistance (MDR, however, are not yet resolved. To evaluate the potential mechanisms, we used whole genome transcriptome and electrospray ionization tandem mass spectrometry (ESI-MS/MS based lipidome analyses of iron deprived Candida cells to examine the new cellular circuitry of the MDR of this pathogen. Our transcriptome data revealed a link between calcineurin signaling and iron homeostasis. Among the several categories of iron deprivation responsive genes, the down regulation of calcineurin signaling genes including HSP90, CMP1 and CRZ1 was noteworthy. Interestingly, iron deprived Candida cells as well as iron acquisition defective mutants phenocopied molecular chaperone HSP90 and calcineurin mutants and thus were sensitive to alkaline pH, salinity and membrane perturbations. In contrast, sensitivity to above stresses did not change in iron deprived DSY2146 strain with a hyperactive allele of calcineurin. Although, iron deprivation phenocopied compromised HSP90 and calcineurin, it was independent of protein kinase C signaling cascade. Notably, the phenotypes associated with iron deprivation in genetically impaired calcineurin and HSP90 could be reversed with iron supplementation. The observed down regulation of ergosterol (ERG1, ERG2, ERG11 and ERG25 and sphingolipid biosynthesis (AUR1 and SCS7 genes followed by lipidome analysis confirmed that iron deprivation not only disrupted ergosterol biosynthesis, but it also affected sphingolipid homeostasis in Candida cells. These lipid compositional changes suggested extensive remodeling of the membranes in iron

  10. Glypican-1 mediates both prion protein lipid raft association and disease isoform formation.

    Directory of Open Access Journals (Sweden)

    David R Taylor

    2009-11-01

    Full Text Available In prion diseases, the cellular form of the prion protein, PrP(C, undergoes a conformational conversion to the infectious isoform, PrP(Sc. PrP(C associates with lipid rafts through its glycosyl-phosphatidylinositol (GPI anchor and a region in its N-terminal domain which also binds to heparan sulfate proteoglycans (HSPGs. We show that heparin displaces PrP(C from rafts and promotes its endocytosis, suggesting that heparin competes with an endogenous raft-resident HSPG for binding to PrP(C. We then utilised a transmembrane-anchored form of PrP (PrP-TM, which is targeted to rafts solely by its N-terminal domain, to show that both heparin and phosphatidylinositol-specific phospholipase C can inhibit its association with detergent-resistant rafts, implying that a GPI-anchored HSPG targets PrP(C to rafts. Depletion of the major neuronal GPI-anchored HSPG, glypican-1, significantly reduced the raft association of PrP-TM and displaced PrP(C from rafts, promoting its endocytosis. Glypican-1 and PrP(C colocalised on the cell surface and both PrP(C and PrP(Sc co-immunoprecipitated with glypican-1. Critically, treatment of scrapie-infected N2a cells with glypican-1 siRNA significantly reduced PrP(Sc formation. In contrast, depletion of glypican-1 did not alter the inhibitory effect of PrP(C on the beta-secretase cleavage of the Alzheimer's amyloid precursor protein. These data indicate that glypican-1 is a novel cellular cofactor for prion conversion and we propose that it acts as a scaffold facilitating the interaction of PrP(C and PrP(Sc in lipid rafts.

  11. Isolation and characterization of a tomato non-specific lipid transfer protein involved in polygalacturonase-mediated pectin degradation.

    Science.gov (United States)

    Tomassen, Monic M M; Barrett, Diane M; van der Valk, Henry C P M; Woltering, Ernst J

    2007-01-01

    An important aspect of the ripening process of tomato fruit is softening. Softening is accompanied by hydrolysis of the pectin in the cell wall by pectinases, causing loss of cell adhesion in the middle lamella. One of the most significant pectin-degrading enzymes is polygalacturonase (PG). Previous reports have shown that PG in tomato may exist in different forms (PG1, PG2a, PG2b, and PGx) commonly referred to as PG isoenzymes. The gene product PG2 is differentially glycosylated and is thought to associate with other proteins to form PG1 and PGx. This association is thought to modulate its pectin-degrading activity in planta. An 8 kDa protein that is part of the tomato PG1 multiprotein complex has been isolated, purified, and functionally characterized. This protein, designated 'activator' (ACT), belongs to the class of non-specific lipid transfer proteins (nsLTPs). ACT is capable of 'converting' the gene product PG2 into a more active and heat-stable form, which increases PG-mediated pectin degradation in vitro and stimulates PG-mediated tissue breakdown in planta. This finding suggests a new, not previously identified, function for nsLTPs in the modification of hydrolytic enzyme activity. It is proposed that ACT plays a role in the modulation of PG activity during tomato fruit softening.

  12. Piper betle and its bioactive metabolite phytol mitigates quorum sensing mediated virulence factors and biofilm of nosocomial pathogen Serratia marcescens in vitro.

    Science.gov (United States)

    Srinivasan, Ramanathan; Devi, Kannan Rama; Kannappan, Arunachalam; Pandian, Shunmugiah Karutha; Ravi, Arumugam Veera

    2016-12-04

    Piper betle, a tropical creeper plant belongs to the family Piperaceae. The leaves of this plant have been well known for their therapeutic, religious and ceremonial value in South and Southeast Asia. It has also been reported to possess several biological activities including antimicrobial, antioxidant, antinociceptive, antidiabetic, insecticidal and gastroprotective activities and used as a common ingredient in indigenous medicines. In Indian system of ayurvedic medicine, P. betle has been well recognized for its antiseptic properties and is commonly applied on wounds and lesions for its healing effects. To evaluate the anti-quorum sensing (anti-QS) and antibiofilm efficacy of P. betle and its bioactive metabolite phytol against Serratia marcescens. The P. betle ethyl acetate extract (PBE) was evaluated for its anti-QS efficacy against S. marcescens by assessing the prodigiosin and lipase production at 400 and 500µgml -1 concentrations. In addition, the biofilm biomass quantification assay was performed to evaluate the antibiofilm activity of PBE against S. marcescens. Besides, the influence of PBE on bacterial biofilm formation was assessed through microscopic techniques. The biofilm related phenomenons like exopolysaccharides (EPS) production, hydrophobicity and swarming motility were also examined to support the antibiofilm activity of PBE. Transcriptional analysis of QS regulated genes in S. marcescens was also done. Characterization of PBE was done by separation through column chromatography and identification of active metabolites by gas chromatography -mass spectrometry. The major compounds of active fractions such as hexadecanoic acid, eugenol and phytol were assessed for their anti-QS activity against S. marcescens. Further, the in vitro bioassays such as protease, biofilm and HI quantification were also carried out to confirm the anti-QS and antibiofilm potential of phytol in PBE. PBE inhibits QS mediated prodigiosin pigment production in S. marcescens

  13. Pex11mediates peroxisomal proliferation by promoting deformation of the lipid membrane

    Directory of Open Access Journals (Sweden)

    Yumi Yoshida

    2015-07-01

    Full Text Available Pex11p family proteins are key players in peroxisomal fission, but their molecular mechanisms remains mostly unknown. In the present study, overexpression of Pex11pβ caused substantial vesiculation of peroxisomes in mammalian cells. This vesicle formation was dependent on dynamin-like protein 1 (DLP1 and mitochondrial fission factor (Mff, as knockdown of these proteins diminished peroxisomal fission after Pex11pβ overexpression. The fission-deficient peroxisomes exhibited an elongated morphology, and peroxisomal marker proteins, such as Pex14p or matrix proteins harboring peroxisomal targeting signal 1, were discernible in a segmented staining pattern, like beads on a string. Endogenous Pex11pβ was also distributed a striped pattern, but which was not coincide with Pex14p and PTS1 matrix proteins. Altered morphology of the lipid membrane was observed when recombinant Pex11p proteins were introduced into proteo-liposomes. Constriction of proteo-liposomes was observed under confocal microscopy and electron microscopy, and the reconstituted Pex11pβ protein localized to the membrane constriction site. Introducing point mutations into the N-terminal amphiphathic helix of Pex11pβ strongly reduced peroxisomal fission, and decreased the oligomer formation. These results suggest that Pex11p contributes to the morphogenesis of the peroxisomal membrane, which is required for subsequent fission by DLP1.

  14. Pex11mediates peroxisomal proliferation by promoting deformation of the lipid membrane

    Science.gov (United States)

    Yoshida, Yumi; Niwa, Hajime; Honsho, Masanori; Itoyama, Akinori; Fujiki, Yukio

    2015-01-01

    Pex11p family proteins are key players in peroxisomal fission, but their molecular mechanisms remains mostly unknown. In the present study, overexpression of Pex11pβ caused substantial vesiculation of peroxisomes in mammalian cells. This vesicle formation was dependent on dynamin-like protein 1 (DLP1) and mitochondrial fission factor (Mff), as knockdown of these proteins diminished peroxisomal fission after Pex11pβ overexpression. The fission-deficient peroxisomes exhibited an elongated morphology, and peroxisomal marker proteins, such as Pex14p or matrix proteins harboring peroxisomal targeting signal 1, were discernible in a segmented staining pattern, like beads on a string. Endogenous Pex11pβ was also distributed a striped pattern, but which was not coincide with Pex14p and PTS1 matrix proteins. Altered morphology of the lipid membrane was observed when recombinant Pex11p proteins were introduced into proteo-liposomes. Constriction of proteo-liposomes was observed under confocal microscopy and electron microscopy, and the reconstituted Pex11pβ protein localized to the membrane constriction site. Introducing point mutations into the N-terminal amphiphathic helix of Pex11pβ strongly reduced peroxisomal fission, and decreased the oligomer formation. These results suggest that Pex11p contributes to the morphogenesis of the peroxisomal membrane, which is required for subsequent fission by DLP1. PMID:25910939

  15. Microneedle-mediated transdermal delivery of nanostructured lipid carriers for alkaloids from Aconitum sinomontanum.

    Science.gov (United States)

    Guo, Teng; Zhang, Yongtai; Li, Zhe; Zhao, Jihui; Feng, Nianping

    2017-09-12

    A combination method using microneedle (MN) pretreatment and nanostructured lipid carriers (NLCs) was developed to improve the transdermal delivery of therapeutics. The MN treatment of the skin and co-administration of NLCs loaded with total alkaloids isolated from Aconitum sinomontanum (AAS-NLCs) significantly increased the skin permeation of the drugs. Fluorescence imaging confirmed that MNs could provide microchannels penetrating the stratum corneum, and delivery of NLCs through the channels led to their deeper permeation. In vivo studies showed that combination of AAS-NLCs with MNs (AAS-NLCs-MN) in transdermal delivery could improve the bioavailability and maintain stable drug concentrations in the blood. Moreover, AAS-NLCs-MN showed benefits in eliminating paw swelling, decreasing inflammation and pain, and regulating immune function in adjuvant arthritis rats. After administration of AAS-NLCs-MN, no skin irritation was observed in rabbits, and electrocardiograms of rats showed improved arrhythmia. These results indicated that the dual approach combining MN insertion and NLCs has the potential to provide safe transdermal delivery and to improve the therapeutic efficacy through sustained release of AAS.

  16. Effect of bioactive substances found in rapeseed, raspberry and strawberry seed oils on blood lipid profile and selected parameters of oxidative status in rats.

    Science.gov (United States)

    Pieszka, Marek; Tombarkiewicz, Barbara; Roman, Adam; Migdał, Władysław; Niedziółka, Jerzy

    2013-11-01

    Rapeseed, strawberry and raspberry seed oils are a rich source of polyunsaturated fatty acids and antioxidants such as tocols, bioflavonoids and phytosterols. The aim of the study was to determine changes in the blood lipid profile of rats fed with rapeseed, strawberry and raspberry seed oils and their effects on selected parameters of oxidative status. The experiment was carried out on male Wistar rats. The oils were administered by oral gavage for 5 weeks once daily at the dose of about 0.8 ml per rat. Blood samples were taken before and after supplementation period. The activity of superoxide dismutase (SOD) and glutathione peroxidase (cGPx) was assessed in erythrocytes and contents of triglycerides (TG), total cholesterol, low-density fraction of cholesterol (LDL) and high-density fraction of cholesterol (HDL) were assessed in plasma. The experiment shows that oils supplemented in the diet for 5 weeks had no significant effect on the level of triglyceride (TG), total cholesterol as well as HDL and LDL fractions. Reduced activity of cGPX and SOD in the group of rats receiving raspberry and strawberry seed oils suggests that these native oils may contribute to oxidative stability (improves antioxidant status). Thus, strawberry and raspberry seed oils can be considered as special biological oils, which constitute potential nutraceuticals reducing oxidative stress. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Novel 1,3-diacylamidopropane-2-[bis-(2-dimethylaminoethane)] carbamate pH-sensitive lipids for cationic liposome-mediated transfection

    Science.gov (United States)

    Spelios, Michael G.

    A novel series of 1,3-diacylamidopropane-2-[bis(2-dimethylaminoethane)] carbamate analogs (1,3lb) were designed for cationic lipid-assisted transfection (lipofection). First, their physicochemical properties in self-assemblies with and without plasmid DNA (pDNA) were evaluated to examine the effects of hydrophobic tail length and degree of saturation on gene delivery and expression. Significant in vitro lipofection was induced at a nitrogen:phosphate ratio (N:P) of 4:1 by the dimyristoyl, dipalmitoyl, and dioleoyl analogs 1,3lb2, 1,3lb3, and 1,3lb5, respectively, without inclusion of neutral "lipofection enhancing" co-lipids in the cationic lipid formulations. Lipofection was reduced in the presence of co-lipids except for 1,3lb5 which maintained reporter gene expression levels at N:P 4:1 and yielded increased bioactivity at a lower NP of 2:1. Physicochemical characterization of the bioactive transfection agents (cytofectins) revealed: high hydration and in-plane elasticity of lipid monolayers by Langmuir film balance measurements; fluid lipid bilayers, with gel---liquid crystalline phase transitions below physiological temperature, by fluorescence anisotropy; lipid mixing with biomembrane-mimicking vesicles by fluorescence resonance energy transfer; efficient pDNA binding and compaction by ethidium bromide displacement; cationic liposome---nucleic acid complexes (lipoplexes) with large particle sizes (mean diameter ≥ 500 nm) and zeta potentials of positive values by dynamic light scattering and electrophoretic mobility, respectively. The results suggest that well hydrated and elastic cationic lipids forming fluid lamellar assemblies are extremely potent and minimally toxic cytofectins. Second, a comparison was made between 1,3lb2 and two derivatives, one an isomer with a shorter space between the myristoyl chains and the other the monovalent form, in an effort to delineate the biological effects of interchain distance and pH-induced polar headgroup expandability

  18. Comparative time-courses of copper-ion-mediated protein and lipid oxidation in low-density lipoprotein

    DEFF Research Database (Denmark)

    Knott, Heather M; Baoutina, Anna; Davies, Michael Jonathan

    2002-01-01

    Free radicals damage both lipids and proteins and evidence has accumulated for the presence of both oxidised lipids and proteins in aged tissue samples as well as those from a variety of pathologies including atherosclerosis, diabetes, and Parkinson's disease. Oxidation of the protein and lipid...

  19. The density of GM1-enriched lipid rafts correlates inversely with the efficiency of transfection mediated by cationic liposomes.

    Science.gov (United States)

    Kovács, Tamás; Kárász, Andrea; Szöllosi, János; Nagy, Peter

    2009-08-01

    Although cationic liposome-mediated transfection has become a standard procedure, the mechanistic details of the process are unknown. It has been suggested that endocytic uptake of lipoplexes is efficient, and transfectability is largely determined by later steps. In this article, we stained GM1-enriched membrane microdomains, a subclass of lipid rafts, with subunit B of cholera toxin and correlated transfection efficiency with their density by quantitatively evaluating microscopic images. We found a strong anticorrelation between the density of GM1-enriched membrane microdomains and the efficacy of transfection monitored by measuring the expression level of GFP in different cell lines transfected by lipofection using two different transfection agents. These findings imply that GM1-enriched membrane microdomains interfere with the process of lipofection. The blocked step must be endocytosis since the accumulation of fluorescently labeled plasmids was lower in cells with high content of GM1-enriched membrane microdomains. Such a correlation was not observed in cells transfected by electroporation. By comparing the efficiency of lipofection in several cell lines we found that those with a high density of GM1-enriched membrane microdomains were the most resistant to transfection. We conclude that the inhibition of lipofection by GM1-enriched membrane microdomains is a general rule, and that endocytosis of lipoplexes can be rate limiting in cells with high density of GM1-enriched membrane rafts. Copyright 2009 International Society for Advancement of Cytometry.

  20. Serum microRNA miR-206 is decreased in hyperthyroidism and mediates thyroid hormone regulation of lipid metabolism in HepG2 human hepatoblastoma cells.

    Science.gov (United States)

    Zheng, Yingjuan; Zhao, Chao; Zhang, Naijian; Kang, Wenqin; Lu, Rongrong; Wu, Huadong; Geng, Yingxue; Zhao, Yaping; Xu, Xiaoyan

    2018-04-01

    The actions of thyroid hormone (TH) on lipid metabolism in the liver are associated with a number of genes involved in lipogenesis and lipid metabolism; however, the underlying mechanisms through which TH impacts on lipid metabolism remain to be elucidated. The present study aimed to investigate the effects of hyperthyroidism on the serum levels of the microRNA (miR) miR‑206 and the role of miR‑206 on TH‑regulated lipid metabolism in liver cells. Serum was obtained from 12 patients diagnosed with hyperthyroidism and 10 healthy control subjects. Human hepatoblastoma (HepG2) cells were used to study the effects of triiodothyronine (T3) and miR‑206 on lipid metabolism. Expression of miR‑206 in serum and cells was determined by reverse transcription‑quantitative polymerase chain reaction analysis. Lipid accumulation in HepG2 cells was assessed with Oil Red O staining. Suppression or overexpression of miR‑206 was performed via transfection with a miR‑206 mimic or miR‑206 inhibitor. Serum miR‑206 was significantly decreased in patients with hyperthyroidism compared with euthyroid controls. Treatment of HepG2 cells with T3 led to reduced total cholesterol (TC) and triglyceride (TG) content, accompanied by reduced miR‑206 expression. Inhibition of endogenous miR‑206 expression decreased intracellular TG and TC content in HepG2 cells. By contrast, overexpression of miR‑206 in HepG2 partially prevented the reduction in TG content induced by treatment with T3. In conclusion, serum miR‑206 expression is reduced in patients with hyperthyroidism. In addition, miR‑206 is involved in T3‑mediated regulation of lipid metabolism in HepG2 cells, indicating a role for miR‑206 in thyroid hormone‑induced disorders of lipid metabolism in the liver.

  1. Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6

    International Nuclear Information System (INIS)

    Penrose, Harrison; Heller, Sandra; Cable, Chloe; Makboul, Rania; Chadalawada, Gita; Chen, Ying; Crawford, Susan E.; Savkovic, Suzana D.

    2016-01-01

    The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTOR and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.

  2. Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6

    Energy Technology Data Exchange (ETDEWEB)

    Penrose, Harrison; Heller, Sandra; Cable, Chloe [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Makboul, Rania [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Pathology Department, Assiut University, Assiut (Egypt); Chadalawada, Gita; Chen, Ying [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Crawford, Susan E. [Department of Pathology, Saint Louis University School of Medicine, 1402 South Grand Blvd, Saint Louis, MO 63104 (United States); Savkovic, Suzana D., E-mail: ssavkovi@tulane.edu [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States)

    2016-01-15

    The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTOR and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.

  3. Agrobacterium rhizogenes mediated transformation of Rhodiola sp. - an approach to enhance the level of bioactive compounds

    DEFF Research Database (Denmark)

    Himmelboe, Martin; Lauridsen, Uffe Bjerre; Hegelund, Josefine Nymark

    2015-01-01

    Rhodiola rosea, commonly known as roseroot, has since ancient times been used against depression and for improving mental abilities because of its bioactive compounds. Due to excessive exploitation, the natural populations have been declining. Natural transformation with root-loci (rol)-genes fro...

  4. Omega-3 fatty acids promote fatty acid utilization and production of pro-resolving lipid mediators in alternatively activated adipose tissue macrophages

    Czech Academy of Sciences Publication Activity Database

    Rombaldová, Martina; Janovská, Petra; Kopecký, Jan; Kuda, Ondřej

    2017-01-01

    Roč. 490, č. 3 (2017), s. 1080-1085 ISSN 0006-291X R&D Projects: GA ČR(CZ) GA16-05151S; GA MŠk(CZ) LTAUSA17173 Institutional support: RVO:67985823 Keywords : adipose tissue * macrophages * omega-3 PUFA * fatty acid re-esterification * lipolysis * lipid mediators Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 2.466, year: 2016

  5. Hedonic Eating and the “Delicious Circle”: From Lipid-Derived Mediators to Brain Dopamine and Back

    Directory of Open Access Journals (Sweden)

    Roberto Coccurello

    2018-04-01

    Full Text Available Palatable food can be seductive and hedonic eating can become irresistible beyond hunger and negative consequences. This is witnessed by the subtle equilibrium between eating to provide energy intake for homeostatic functions, and reward-induced overeating. In recent years, considerable efforts have been devoted to study neural circuits, and to identify potential factors responsible for the derangement of homeostatic eating toward hedonic eating and addiction-like feeding behavior. Here, we examined recent literature on “old” and “new” players accountable for reward-induced overeating and possible liability to eating addiction. Thus, the role of midbrain dopamine is positioned at the intersection between selected hormonal signals involved in food reward information processing (namely, leptin, ghrelin, and insulin, and lipid-derived neural mediators such as endocannabinoids. The impact of high fat palatable food and dietary lipids on endocannabinoid formation is reviewed in its pathogenetic potential for the derangement of feeding homeostasis. Next, endocannabinoid signaling that regulates synaptic plasticity is discussed as a key mechanism acting both at hypothalamic and mesolimbic circuits, and affecting both dopamine function and interplay between leptin and ghrelin signaling. Outside the canonical hypothalamic feeding circuits involved in energy homeostasis and the notion of “feeding center,” we focused on lateral hypothalamus as neural substrate able to confront food-associated homeostatic information with food salience, motivation to eat, reward-seeking, and development of compulsive eating. Thus, the lateral hypothalamus-ventral tegmental area-nucleus accumbens neural circuitry is reexamined in order to interrogate the functional interplay between ghrelin, dopamine, orexin, and endocannabinoid signaling. We suggested a pivotal role for endocannabinoids in food reward processing within the lateral hypothalamus, and for orexin

  6. Inefficient cationic lipid-mediated siRNA and antisense oligonucleotide transfer to airway epithelial cells in vivo

    Directory of Open Access Journals (Sweden)

    Hu Jim

    2006-02-01

    Full Text Available Abstract Background The cationic lipid Genzyme lipid (GL 67 is the current "gold-standard" for in vivo lung gene transfer. Here, we assessed, if GL67 mediated uptake of siRNAs and asODNs into airway epithelium in vivo. Methods Anti-lacZ and ENaC (epithelial sodium channel siRNA and asODN were complexed to GL67 and administered to the mouse airway epithelium in vivo Transfection efficiency and efficacy were assessed using real-time RT-PCR as well as through protein expression and functional studies. In parallel in vitro experiments were carried out to select the most efficient oligonucleotides. Results In vitro, GL67 efficiently complexed asODNs and siRNAs, and both were stable in exhaled breath condensate. Importantly, during in vitro selection of functional siRNA and asODN we noted that asODNs accumulated rapidly in the nuclei of transfected cells, whereas siRNAs remained in the cytoplasm, a pattern consistent with their presumed site of action. Following in vivo lung transfection siRNAs were only visible in alveolar macrophages, whereas asODN also transfected alveolar epithelial cells, but no significant uptake into conducting airway epithelial cells was seen. SiRNAs and asODNs targeted to β-galactosidase reduced βgal mRNA levels in the airway epithelium of K18-lacZ mice by 30% and 60%, respectively. However, this was insufficient to reduce protein expression. In an attempt to increase transfection efficiency of the airway epithelium, we increased contact time of siRNA and asODN using the in vivo mouse nose model. Although highly variable and inefficient, transfection of airway epithelium with asODN, but not siRNA, was now seen. As asODNs more effectively transfected nasal airway epithelial cells, we assessed the effect of asODN against ENaC, a potential therapeutic target in cystic fibrosis; no decrease in ENaC mRNA levels or function was detected. Conclusion This study suggests that although siRNAs and asODNs can be developed to inhibit

  7. Melatonin-induced increase of lipid droplets accumulation and in vitro maturation in porcine oocytes is mediated by mitochondrial quiescence.

    Science.gov (United States)

    He, Bin; Yin, Chao; Gong, Yabin; Liu, Jie; Guo, Huiduo; Zhao, Ruqian

    2018-01-01

    Melatonin, the major pineal secretory product, has a significant impact on the female reproductive system. Recently, the beneficial effects of melatonin on mammalian oocyte maturation and embryonic development have drawn increased attention. However, the exact underlying mechanisms remain to be fully elucidated. This study demonstrates that supplementing melatonin to in vitro maturation (IVM) medium enhances IVM rate, lipid droplets (LDs) accumulation as well as triglyceride content in porcine oocytes. Decrease of mitochondrial membrane potential, mitochondrial respiratory chain complex IV activity as well as mitochondrial reactive oxygen species (mROS) content indicated that melatonin induced a decrease of mitochondrial activity. The copy number of mitochondrial DNA (mtDNA) which encodes essential subunits of oxidative phosphorylation (OXPHOS), was not affected by melatonin. However, the expression of mtDNA-encoded genes was significantly down-regulated after melatonin treatment. The DNA methyltransferase DNMT1, which regulates methylation and expression of mtDNA, was increased and translocated into the mitochondria in melatonin-treated oocytes. The inhibitory effect of melatonin on the expression of mtDNA was significantly prevented by simultaneous addition of DNMT1 inhibitor, which suggests that melatonin regulates the transcription of mtDNA through up-regulation of DNMT1 and mtDNA methylation. Increase of triglyceride contents after inhibition of OXPHOS indicated that mitochondrial quiescence is crucial for LDs accumulation in oocytes. Taken together, our results suggest that melatonin-induced reduction in mROS production and increase in IVM, and LDs accumulation in porcine oocytes is mediated by mitochondrial quiescence. © 2017 Wiley Periodicals, Inc.

  8. P2X1 receptors localized in lipid rafts mediate ATP motor responses in the human vas deferens longitudinal muscles.

    Science.gov (United States)

    Donoso, María Verónica; Norambuena, Andrés; Navarrete, Camilo; Poblete, Inés; Velasco, Alfredo; Huidobro-Toro, Juan Pablo

    2014-02-01

    To assess the role of the P2X1 receptors (P2X1R) in the longitudinal and circular layers of the human vas deferens, ex vivo-isolated strips or rings were prepared from tissue biopsies to record isometric contractions. To ascertain its membrane distribution, tissue extracts were analyzed by immunoblotting following sucrose gradient ultracentrifugation. ATP, alpha,beta-methylene ATP, or electrical field stimulation elicited robust contractions of the longitudinal layer but not of the circular layer which demonstrated inconsistent responses. Alpha,beta-methylene ATP generated stronger and more robust contractions than ATP. In parallel, prostatic segments of the rat vas deferens were examined. The motor responses in both species were not sustained but decayed within the first minute, showing desensitization to additional applications. Cross-desensitization was established between alpha,beta-methylene ATP or ATP-evoked contractions and electrical field stimulation-induced contractions. Full recovery of the desensitized motor responses required more than 30 min and showed a similar pattern in human and rat tissues. Immunoblot analysis of the human vas deferens extracts revealed a P2X1R oligomer of approximately 200 kDa under nonreducing conditions, whereas dithiothreitol-treated extracts showed a single band of approximately 70 kDa. The P2X1R was identified in ultracentrifugation fractions containing 15%-29% sucrose; the receptor localized in the same fractions as flotillin-1, indicating that it regionalized into smooth muscle lipid rafts. In conclusion, ATP plays a key role in human vas deferens contractile responses of the longitudinal smooth muscle layer, an effect mediated through P2X1Rs.

  9. Study of lipid profile and parieto-temporal lipid peroxidation in AlCl3 mediated neurotoxicity. modulatory effect of fenugreek seeds

    Directory of Open Access Journals (Sweden)

    Belaïd-Nouira Yosra

    2012-01-01

    Full Text Available Abstract Background Peroxidation of lipid (LPO membrane and cholesterol metabolism have been involved in the physiopathology of many diseases of aging brain. Therefore, this prospective animal study was carried firstly to find out the correlation between LPO in posterior brain and plasmatic cholesterol along with lipoprotein levels after chronic intoxication by aluminium chloride (AlCl3. Chronic aluminum-induced neurotoxicity has been in fact related to enhanced brain lipid peroxidation together with hypercholesterolemia and hypertriglyceridemia, despite its controversial etiological role in neurodegenerative diseases. Secondly an evaluation of the effectiveness of fenugreek seeds in alleviating the engendered toxicity through these biochemical parameters was made. Results Oral administration of AlCl3 to rats during 5 months (500 mg/kg bw i.g for one month then 1600 ppm via the drinking water enhanced the levels of LPO in posterior brain, liver and plasma together with lactate dehydrogenase (LDH activities, total cholesterol (TC, triglycerides (TG and LDL-C (Low Density Lipoproteins levels. All these parameters were decreased following fenugreek seeds supplementation either as fenugreek seed powder (FSP or fenugreek seed extract (FSE. A notable significant correlation was observed between LPObrain and LDL-C on one hand and LDHliver on the other hand. This latter was found to correlate positively with TC, TG and LDL-C. Furthermore, high significant correlations were observed between LDHbrain and TC, TG, LDL-C, LPObrain as well as LDHliver. Conclusion Aluminium-induced LPO in brain could arise from alteration of lipid metabolism particularly altered lipoprotein metabolism rather than a direct effect of cholesterol oxidation. Fenugreek seeds could play an anti-peroxidative role in brain which may be attributed in part to its modulatory effect on plasmatic lipid metabolism.

  10. Quinazoline derivatives: synthesis and bioactivities

    OpenAIRE

    Wang, Dan; Gao, Feng

    2013-01-01

    Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. This review summarizes the recent advances in the synthesis and biological activities investigations of quinazoline derivatives. According to the main method the authors adopted in their research design, those synthetic methods were divided into five main classifications, including Aza-reaction, Microwave-assisted reaction, Metal-mediated reac...

  11. Adsorption and Orientation of Human Islet Amyloid Polypeptide (hIAPP Monomer at Anionic Lipid Bilayers: Implications for Membrane-Mediated Aggregation

    Directory of Open Access Journals (Sweden)

    Guanghong Wei

    2013-03-01

    Full Text Available Protein misfolding and aggregation cause serious degenerative diseases, such as Alzheimer’s and type II diabetes. Human islet amyloid polypeptide (hIAPP is the major component of amyloid deposits found in the pancreas of type II diabetic patients. Increasing evidence suggests that β-cell death is related to the interaction of hIAPP with the cellular membrane, which accelerates peptide aggregation. In this study, as a first step towards understanding the membrane-mediated hIAPP aggregation, we investigate the atomic details of the initial step of hIAPP-membrane interaction, including the adsorption orientation and conformation of hIAPP monomer at an anionic POPG lipid bilayer by performing all-atom molecular dynamics simulations. We found that hIAPP monomer is quickly adsorbed to bilayer surface, and the adsorption is initiated from the N-terminal residues driven by strong electrostatic interactions of the positively-charged residues K1 and R11 with negatively-charged lipid headgroups. hIAPP binds parallel to the lipid bilayer surface as a stable helix through residues 7–22, consistent with previous experimental study. Remarkably, different simulations lead to the same binding orientation stabilized by electrostatic and H-bonding interactions, with residues R11, F15 and S19 oriented towards membrane and hydrophobic residues L12, A13, L16 and V17 exposed to solvent. Implications for membrane-mediated hIAPP aggregation are discussed.

  12. Bioactive lipids as key regulators in atherosclerosis

    NARCIS (Netherlands)

    Bot, Martine

    2009-01-01

    Scheuring van een vaatwandvernauwing (plaque) kan ertoe leiden dat materiaal vanuit deze plaques in direct contact komt met de bloedsomloop wat de bloedstolling kan activeren met als mogelijk gevolg bloedvatafsluiting en hartinfarct. Vooral vetten zoals het lysofosfatidaat (LPA) in deze plaques zijn

  13. Inhibitory effect of Piper betel leaf extracts on copper-mediated LDL oxidation and oxLDL-induced lipid accumulation via inducing reverse cholesterol transport in macrophages.

    Science.gov (United States)

    Ma, Gwo-Chin; Wu, Pei-Fang; Tseng, Hsien-Chun; Chyau, Charng-Cherng; Lu, Hsiu-Chin; Chou, Fen-Pi

    2013-12-15

    Piper betel leaf (PBL) has the biological capabilities of detoxification and can work as an anti-inflammatory agent and an anti-oxidant. In this study, we evaluated the anti-oxidative activity of the extract of Piper betel leaves (PBLs) on the basis of Cu(2+)-mediated oxidation, and its ability to prevent foam cell formation in a model for oxidised low density lipoprotein (oxLDL)-induced lipid accumulation in macrophages. Our data demonstrated that PBLs were able to inhibit LDL oxidation in vitro and are able to reduce the lipid accumulation in macrophages. We showed the underlying mechanisms to be the following: PBLs up-regulated the protein levels of the class A and class B scavenger receptors, the membrane lipid transporter ABCA1, and its upstream regulator Liver X receptor (LXR) in the macrophages exposed to oxLDL. The results suggested that PBLs activated the reverse cholesterol transport mechanism to enhance the metabolism of the oxLDL that could prevent both lipid accumulation and foam cell formation and further minimise the possible damage of vessels caused by the oxLDL. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. CD1d-mediated presentation of endogenous lipid antigens by adipocytes requires microsomal triglyceride transfer protein (MTP)

    DEFF Research Database (Denmark)

    Rakhshandehroo, Maryam; Gijzel, Sanne M W; Siersbæk, Rasmus

    2014-01-01

    -dependent fashion, but little is known about the lipid antigen presentation machinery in adipocytes. Here we show that CD1d, as well as the lipid antigen loading machinery genes pro-saposin (Psap), Niemann Pick type C2 (Npc2), α-galactosidase (Gla), are upregulated in early adipogenesis, and are transcriptionally...... presenting cells (APCs), which may present an important aspect of adipocyte-immune cell communication in the regulation of whole body energy metabolism and immune homeostasis....

  15. Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF-1/IGF-1R signaling.

    Science.gov (United States)

    Shi, Haojun; Fang, Winston; Liu, Minda; Fu, Deliang

    2017-10-01

    Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF-1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF-1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF-1/IGF-1R-induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF-1/IGF-1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies. © 2017 UICC.

  16. PPARα, PPARγ and SREBP-1 pathways mediated waterborne iron (Fe)-induced reduction in hepatic lipid deposition of javelin goby Synechogobius hasta.

    Science.gov (United States)

    Chen, Guang-Hui; Luo, Zhi; Chen, Feng; Shi, Xi; Song, Yu-Feng; You, Wen-Jing; Liu, Xu

    2017-07-01

    and up-regulating lipolysis, and PPARα, PPARγ and SREBP-1 pathways mediated the Fe-induced reduction of hepatic lipid deposition in S. hasta. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Formation of milk lipids: a molecular perspective

    OpenAIRE

    McManaman, James L

    2009-01-01

    Lipids, primarily triglycerides, are major milk constituents of most mammals, providing a large percentage of calories, essential fatty acids and bioactive lipids required for neonatal growth and development. To meet the caloric and nutritional demands of newborns, the mammary glands of most species have evolved an enormous capacity to synthesize and secrete large quantities of lipids during lactation. Significant information exists regarding the physiological regulation of lipid metabolism i...

  18. Exosome uptake depends on ERK1/2-heat shock protein 27 signaling and lipid Raft-mediated endocytosis negatively regulated by caveolin-1.

    Science.gov (United States)

    Svensson, Katrin J; Christianson, Helena C; Wittrup, Anders; Bourseau-Guilmain, Erika; Lindqvist, Eva; Svensson, Lena M; Mörgelin, Matthias; Belting, Mattias

    2013-06-14

    The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signaling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signaling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft-associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several downstream targets known to associate with lipid rafts as signaling and sorting platforms, such as extracellular signal-regulated kinase-1/2 (ERK1/2) and heat shock protein 27 (HSP27). Interestingly, exosome uptake appears dependent on unperturbed ERK1/2-HSP27 signaling, and ERK1/2 phosphorylation is under negative influence by CAV1 during internalization of exosomes. These findings significantly advance our general understanding of exosome-mediated uptake and offer potential strategies for how this pathway may be targeted through modulation of CAV1 expression and ERK1/2 signaling.

  19. Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/ Rho kinase pathways targeted to lipid rafts.

    Science.gov (United States)

    Burger, Dylan; Montezano, Augusto C; Nishigaki, Nobuhiro; He, Ying; Carter, Anthony; Touyz, Rhian M

    2011-08-01

    Circulating microparticles are increased in cardiovascular disease and may themselves promote oxidative stress and inflammation. Molecular mechanisms underlying their formation and signaling are unclear. We investigated the role of reactive oxygen species (ROS), Rho kinase, and lipid rafts in microparticle formation and examined their functional significance in endothelial cells (ECs). Microparticle formation from angiotensin II (Ang II)-stimulated ECs and apolipoprotein E(-/-) mice was assessed by annexin V or by CD144 staining and electron microscopy. Ang II promoted microparticle formation and increased EC O(2)(-) generation and Rho kinase activity. Ang II-stimulated effects were inhibited by irbesartan (Ang II receptor type I blocker) and fasudil (Rho kinase inhibitor). Methyl-β-cyclodextrin and nystatin, which disrupt lipid rafts/caveolae, blocked microparticle release. Functional responses, assessed in microparticle-stimulated ECs, revealed increased O(2)(-) production, enhanced vascular cell adhesion molecule/platelet-EC adhesion molecule expression, and augmented macrophage adhesion. Inhibition of epidermal growth factor receptor blocked the prooxidative and proinflammatory effects of microparticles. In vitro observations were confirmed in apolipoprotein E(-/-) mice, which displayed vascular inflammation and high levels of circulating endothelial microparticles, effects that were reduced by apocynin. We demonstrated direct actions of Ang II on endothelial microparticle release, mediated through NADPH oxidase, ROS, and Rho kinase targeted to lipid rafts. Microparticles themselves stimulated endothelial ROS formation and inflammatory responses. Our findings suggest a feedforward system whereby Ang II promotes EC injury through its own endothelial-derived microparticles.

  20. Indication of bioactive candidates among body volatiles of ...

    African Journals Online (AJOL)

    Gregarious adult locusts are believed to release many bioactive volatiles from their bodies for the mediation of their biological characteristics. The determination of these bioactive body volatiles can contribute to the development of new, environmentally benign methods of locust control. An important locust, Locusta ...

  1. A comparison of heart rate variability, n-3 PUFA status and lipid mediator profile in age- and BMI-matched middle-aged vegans and omnivores.

    Science.gov (United States)

    Pinto, Ana M; Sanders, Thomas A B; Kendall, Alexandra C; Nicolaou, Anna; Gray, Robert; Al-Khatib, Haya; Hall, Wendy L

    2017-03-01

    Low heart rate variability (HRV) predicts sudden cardiac death. Long-chain (LC) n-3 PUFA (C20-C22) status is positively associated with HRV. This cross-sectional study investigated whether vegans aged 40-70 years (n 23), whose diets are naturally free from EPA (20 : 5n-3) and DHA (22 : 6n-3), have lower HRV compared with omnivores (n 24). Proportions of LC n-3 PUFA in erythrocyte membranes, plasma fatty acids and concentrations of plasma LC n-3 PUFA-derived lipid mediators were significantly lower in vegans. Day-time interbeat intervals (IBI), adjusted for physical activity, age, BMI and sex, were significantly shorter in vegans compared with omnivores (mean difference -67 ms; 95 % CI -130, -3·4, P50 % and high-frequency power) were similarly lower in vegans, with no differences during sleep. In conclusion, vegans have higher 24 h SDNN, but lower day-time HRV and shorter day-time IBI relative to comparable omnivores. Vegans may have reduced availability of precursor markers for pro-resolving lipid mediators; it remains to be determined whether there is a direct link with impaired cardiac function in populations with low-n-3 status.

  2. Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts

    Czech Academy of Sciences Publication Activity Database

    Psahoulia, F.H.; Drosopoulos, K.G.; Doubravská, Lenka; Anděra, Ladislav; Pintzas, A.

    2007-01-01

    Roč. 6, č. 9 (2007), s. 2591-2599 ISSN 1535-7163 R&D Projects: GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50520514 Keywords : TRAIL * apoptosis * lipid rafts Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.800, year: 2007

  3. Investigations of antioxidant-mediated protection and mitigation of radiation-induced DNA damage and lipid peroxidation in murine skin.

    Science.gov (United States)

    Jelveh, Salomeh; Kaspler, Pavel; Bhogal, Nirmal; Mahmood, Javed; Lindsay, Patricia E; Okunieff, Paul; Doctrow, Susan R; Bristow, Robert G; Hill, Richard P

    2013-08-01

    Radioprotection and mitigation effects of the antioxidants, Eukarion (EUK)-207, curcumin, and the curcumin analogs D12 and D68, on radiation-induced DNA damage or lipid peroxidation in murine skin were investigated. These antioxidants were studied because they have been previously reported to protect or mitigate against radiation-induced skin reactions. DNA damage was assessed using two different assays. A cytokinesis-blocked micronucleus (MN) assay was performed on primary skin fibroblasts harvested from the skin of C3H/HeJ male mice 1 day, 1 week and 4 weeks after 5 Gy or 10 Gy irradiation. Local skin or whole body irradiation (100 kVp X-rays or caesium (Cs)-137 γ-rays respectively) was performed. DNA damage was further quantified in keratinocytes by immunofluorescence staining of γ-histone 2AX (γ-H2AX) foci in formalin-fixed skin harvested 1 hour or 1 day post-whole body irradiation. Radiation-induced lipid peroxidation in the skin was investigated at the same time points as the MN assay by measuring malondialdehyde (MDA) with a Thiobarbituric acid reactive substances (TBARS) assay. None of the studied antioxidants showed significant mitigation of skin DNA damage induced by local irradiation. However, when EUK-207 or curcumin were delivered before irradiation they provided some protection against DNA damage. In contrast, all the studied antioxidants demonstrated significant mitigating and protecting effects on radiation-induced lipid peroxidation at one or more of the three time points after local skin irradiation. Our results show no evidence for mitigation of DNA damage by the antioxidants studied in contrast to mitigation of lipid peroxidation. Since these agents have been reported to mitigate skin reactions following irradiation, the data suggest that changes in lipid peroxidation levels in skin may reflect developing skin reactions better than residual post-irradiation DNA damage in skin cells. Further direct comparison studies are required to confirm

  4. Direct control of peripheral lipid deposition by CNS GLP-1 receptor signaling is mediated by the sympathetic nervous system and blunted in diet-induced obesity.

    Science.gov (United States)

    Nogueiras, Ruben; Pérez-Tilve, Diego; Veyrat-Durebex, Christelle; Morgan, Donald A; Varela, Luis; Haynes, William G; Patterson, James T; Disse, Emmanuel; Pfluger, Paul T; López, Miguel; Woods, Stephen C; DiMarchi, Richard; Diéguez, Carlos; Rahmouni, Kamal; Rohner-Jeanrenaud, Françoise; Tschöp, Matthias H

    2009-05-06

    We investigated a possible role of the central glucagon-like peptide (GLP-1) receptor system as an essential brain circuit regulating adiposity through effects on nutrient partitioning and lipid metabolism independent from feeding behavior. Both lean and diet-induced obesity mice were used for our experiments. GLP-1 (7-36) amide was infused in the brain for 2 or 7 d. The expression of key enzymes involved in lipid metabolism was measured by real-time PCR or Western blot. To test the hypothesis that the sympathetic nervous system may be responsible for informing adipocytes about changes in CNS GLP-1 tone, we have performed direct recording of sympathetic nerve activity combined with experiments in genetically manipulated mice lacking beta-adrenergic receptors. Intracerebroventricular infusion of GLP-1 in mice directly and potently decreases lipid storage in white adipose tissue. These effects are independent from nutrient intake. Such CNS control of adipocyte metabolism was found to depend partially on a functional sympathetic nervous system. Furthermore, the effects of CNS GLP-1 on adipocyte metabolism were blunted in diet-induced obese mice. The CNS GLP-1 system decreases fat storage via direct modulation of adipocyte metabolism. This CNS GLP-1 control of adipocyte lipid metabolism appears to be mediated at least in part by the sympathetic nervous system and is independent of parallel changes in food intake and body weight. Importantly, the CNS GLP-1 system loses the capacity to modulate adipocyte metabolism in obese states, suggesting an obesity-induced adipocyte resistance to CNS GLP-1.

  5. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  6. Alterations in Lipid Mediated Signaling and Wnt/β-Catenin Signaling in DMH Induced Colon Cancer on Supplementation of Fish Oil

    Directory of Open Access Journals (Sweden)

    Shevali Kansal

    2014-01-01

    Full Text Available Ceramide mediates inhibition of cyclooxygenase-2 (COX-2 which catalyzes formation of prostaglandin further activating peroxisome proliferator-activated receptorγ (PPARγ and Wnt/β-catenin pathway; and hence plays a critical role in cancer. Therefore, in current study, ceramide, COX-2, 15-deoxy prostaglandin J2(15-deoxy PGJ2, PPARγ, and β-catenin were estimated to evaluate the effect of fish oil on lipid mediated and Wnt/β-catenin signaling in colon carcinoma. Male Wistar rats in Group I received purified diet while Groups II and III received modified diet supplemented with FO : CO(1 : 1 and FO : CO(2.5 : 1, respectively. These were further subdivided into controls receiving ethylenediaminetetraacetic acid and treated groups receiving dimethylhydrazine dihydrochloride (DMH/week for 4 weeks. Animals sacrificed 48 hours after last injection constituted initiation phase and those sacrificed after 16 weeks constituted postinitiation phase. Decreased ceramide and increased PPARγ were observed in postinitiation phase only. On receiving FO+CO(1 : 1+DMH and FO+CO(2.5 : 1+DMH in both phases, ceramide was augmented whereas COX-2, 15-deoxy PGJ2, and nuclear translocation of β-catenin were reduced with respect to cancerous animals. Decrease was more significant in postinitiation phase with FO+CO(2.5 : 1+DMH. Treatment with oils increased PPARγ in initiation phase but decreased it in postinitiation phase. Hence, fish oil altered lipid mediated signalling in a dose and time dependent manner so as to inhibit progression of colon cancer.

  7. Biosynthesis, characterization, and evaluation of bioactivities of leaf extract-mediated biocompatible silver nanoparticles from an early tracheophyte, Pteris tripartita Sw.

    Science.gov (United States)

    Baskaran, Xavierravi; Geo Vigila, Antony Varuvel; Parimelazhagan, Thangaraj; Muralidhara-Rao, Doulathabad; Zhang, Shouzhou

    2016-01-01

    The objective of the study was to characterize silver nanoparticles (Ag-NPs) and their bioactivities in early tracheophytes (Pteridophyta). Aqueous leaf extract of a critically endangered fern, Pteris tripartita Sw., was used for one-step green synthesis of Ag-NPs. The biosynthesized Ag-NPs were characterized using ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and high-resolution transmission electron microscopy. Morphologically, the Ag-NPs showed hexagonal, spherical, and rod-shaped structures. Size distributions of Ag-NPs, calculated using Scherrer’s formula, showed an average size of 32 nm. Ag-NPs were studied for in vitro antioxidant, antimicrobial, and in vivo anti-inflammatory activities. Ag-NPs exhibited significant anti-inflammatory activity in carrageenan-induced paw volume tests performed in female Wistar albino rats. Furthermore, Ag-NPs showed significant antimicrobial activity against 12 different microorganisms in three different assays (disk diffusion, time course growth, and minimum inhibitory concentration). This study reports that colloidal Ag-NPs can be synthesized by simple, nonhazardous methods, and that biosynthesized Ag-NPs have significant therapeutic properties. PMID:27895478

  8. Avanti lipid tools: connecting lipids, technology, and cell biology.

    Science.gov (United States)

    Sims, Kacee H; Tytler, Ewan M; Tipton, John; Hill, Kasey L; Burgess, Stephen W; Shaw, Walter A

    2014-08-01

    Lipid research is challenging owing to the complexity and diversity of the lipidome. Here we review a set of experimental tools developed for the seasoned lipid researcher, as well as, those who are new to the field of lipid research. Novel tools for probing protein-lipid interactions, applications for lipid binding antibodies, enhanced systems for the cellular delivery of lipids, improved visualization of lipid membranes using gold-labeled lipids, and advances in mass spectrometric analysis techniques will be discussed. Because lipid mediators are known to participate in a host of signal transduction and trafficking pathways within the cell, a comprehensive lipid toolbox that aids the science of lipidomics research is essential to better understand the molecular mechanisms of interactions between cellular components. This article is part of a Special Issue entitled Tools to study lipid functions. Copyright © 2014. Published by Elsevier B.V.

  9. In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

    DEFF Research Database (Denmark)

    Gjetting, Torben; Arildsen, Nicolai Skovbjerg; Christensen, Camilla Laulund

    2010-01-01

    DOTAP/cholesterol-based lipoplexes are successfully used for delivery of plasmid DNA in vivo especially to the lungs, although low systemic stability and circulation have been reported. To achieve the aim of discovering the best method for systemic delivery of DNA to disseminated tumors we evalua...... evaluated the potential of formulating DOTAP/cholesterol lipoplexes with a polyethylene glycol (PEG)-modified lipid, giving the benefit of the shielding and stabilizing properties of PEG in the bloodstream....

  10. Biosynthesis, characterization, and evaluation of bioactivities of leaf extract-mediated biocompatible silver nanoparticles from an early tracheophyte, Pteris tripartita Sw.

    Directory of Open Access Journals (Sweden)

    Baskaran XR

    2016-11-01

    Full Text Available Xavierravi Baskaran,1 Antony Varuvel Geo Vigila,2 Thangaraj Parimelazhagan,3 Doulathabad Muralidhara-Rao,4 Shouzhou Zhang1 1Shenzhen Key Laboratory of Southern Subtropical Plant Diversity, Fairy Lake Botanical Garden, Shenzhen and Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 2Department of Zoology, St Xavier’s College, Palayamkottai, 3Department of Botany, Bioprospecting Laboratory, Bharathiar University, Coimbatore, Tamil Nadu, 4Department of Biotechnology, Sri Krishnadevaraya University, Anantapur, Andhra Pradesh, IndiaAbstract: The objective of the study was to characterize silver nanoparticles (Ag-NPs and their bioactivities in early tracheophytes (Pteridophyta. Aqueous leaf extract of a critically endangered fern, Pteris tripartita Sw., was used for one-step green synthesis of Ag-NPs. The biosynthesized Ag-NPs were characterized using ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and high-resolution transmission electron microscopy. Morphologically, the Ag-NPs showed hexagonal, spherical, and rod-shaped structures. Size distributions of Ag-NPs, calculated using Scherrer’s formula, showed an average size of 32 nm. Ag-NPs were studied for in vitro antioxidant, antimicrobial, and in vivo anti-inflammatory activities. Ag-NPs exhibited significant anti-inflammatory activity in carrageenan-induced paw volume tests performed in female Wistar albino rats. Furthermore, Ag-NPs showed significant antimicrobial activity against 12 different microorganisms in three different assays (disk diffusion, time course growth, and minimum inhibitory concentration. This study reports that colloidal Ag-NPs can be synthesized by simple, nonhazardous methods, and that biosynthesized Ag-NPs have significant therapeutic properties.Keywords: silver nanoparticles, Pteris tripartita, FTIR, HRTEM, antioxidant, antimicrobial

  11. Abca12-mediated lipid transport and Snap29-dependent trafficking of lamellar granules are crucial for epidermal morphogenesis in a zebrafish model of ichthyosis

    Directory of Open Access Journals (Sweden)

    Qiaoli Li

    2011-11-01

    Zebrafish (Danio rerio can serve as a model system to study heritable skin diseases. The skin is rapidly developed during the first 5–6 days of embryonic growth, accompanied by expression of skin-specific genes. Transmission electron microscopy (TEM of wild-type zebrafish at day 5 reveals a two-cell-layer epidermis separated from the underlying collagenous stroma by a basement membrane with fully developed hemidesmosomes. Scanning electron microscopy (SEM reveals an ordered surface contour of keratinocytes with discrete microridges. To gain insight into epidermal morphogenesis, we have employed morpholino-mediated knockdown of the abca12 and snap29 genes, which are crucial for secretion of lipids and intracellular trafficking of lamellar granules, respectively. Morpholinos, when placed on exon-intron junctions, were >90% effective in preventing the corresponding gene expression when injected into one- to four-cell-stage embryos. By day 3, TEM of abca12 morphants showed accumulation of lipid-containing electron-dense lamellar granules, whereas snap29 morphants showed the presence of apparently empty vesicles in the epidermis. Evaluation of epidermal morphogenesis by SEM revealed similar perturbations in both cases in the microridge architecture and the development of spicule-like protrusions on the surface of keratinocytes. These morphological findings are akin to epidermal changes in harlequin ichthyosis and CEDNIK syndrome, autosomal recessive keratinization disorders due to mutations in the ABCA12 and SNAP29 genes, respectively. The results indicate that interference of independent pathways involving lipid transport in the epidermis can result in phenotypically similar perturbations in epidermal morphogenesis, and that these fish mutants can serve as a model to study the pathomechanisms of these keratinization disorders.

  12. Cd1b-Mediated T Cell Recognition of a Glycolipid Antigen Generated from Mycobacterial Lipid and Host Carbohydrate during Infection

    Science.gov (United States)

    Moody, D. Branch; Guy, Mark R.; Grant, Ethan; Cheng, Tan-Yun; Brenner, Michael B.; Besra, Gurdyal S.; Porcelli, Steven A.

    2000-01-01

    T cells recognize microbial glycolipids presented by CD1 proteins, but there is no information regarding the generation of natural glycolipid antigens within infected tissues. Therefore, we determined the molecular basis of CD1b-restricted T cell recognition of mycobacterial glycosylated mycolates, including those produced during tissue infection in vivo. Transfection of the T cell receptor (TCR) α and β chains from a glucose monomycolate (GMM)-specific T cell line reconstituted GMM recognition in TCR-deficient T lymphoblastoma cells. This TCR-mediated response was highly specific for natural mycobacterial glucose-6-O-(2R, 3R) monomycolate, including the precise structure of the glucose moiety, the stereochemistry of the mycolate lipid, and the linkage between the carbohydrate and the lipid. Mycobacterial production of antigenic GMM absolutely required a nonmycobacterial source of glucose that could be supplied by adding glucose to media at concentrations found in mammalian tissues or by infecting tissue in vivo. These results indicate that mycobacteria synthesized antigenic GMM by coupling mycobacterial mycolates to host-derived glucose. Specific T cell recognition of an epitope formed by interaction of host and pathogen biosynthetic pathways provides a mechanism for immune response to those pathogenic mycobacteria that have productively infected tissues, as distinguished from ubiquitous, but innocuous, environmental mycobacteria. PMID:11015438

  13. Dual acylation and lipid raft association of Src-family protein tyrosine kinases are required for SDF-1/CXCL12-mediated chemotaxis in the Jurkat human T cell lymphoma cell line.

    Science.gov (United States)

    Zaman, Sabiha N; Resek, Mary E; Robbins, Stephen M

    2008-10-01

    Chemokines play pivotal roles in regulating a wide variety of biological processes by modulating cell migration and recruitment. Deregulation of chemokine signaling can alter cell recruitment, contributing to the pathogenic states associated with autoimmune disease, inflammatory disorders, and sepsis. During chemotaxis, lipid rafts and their resident signaling molecules have been demonstrated to partition to different parts of the cell. Herein, we investigated the role of lipid raft resident Src-family kinases (SFK) in stromal cell-derived factor 1/CXCL12-mediated chemotaxis. We have shown that Lck-deficient J.CaM 1.6 cells are defective in CXCL12-mediated chemotaxis in contrast to their parental counterpart, Jurkat cells. Ectopic expression of the SFK hematopoietic cell kinase (Hck) in J.CaM 1.6 cells reconstituted CXCL12 responsiveness. The requirement of lipid raft association of SFK was assessed using both isoforms of Hck: the dually acylated p59(Hck) isoform that is targeted to lipid rafts and the monoacylated p61(Hck) isoform that is nonraft-associated. We have shown using several gain and loss of acylation alleles that dual acylation of Hck was required for CXCL12-mediated chemotaxis in J.CaM 1.6 cells. These results highlight the importance of the unique microenvironment provided by lipid rafts and their specific contribution in providing specificity to CXCL12 signaling.

  14. 3-Iodothyronamine-mediated metabolic suppression increases the phosphorylation of AMPK and induces fuel choice toward lipid mobilization.

    Science.gov (United States)

    Ju, H; Shin, H; Son, C; Park, K; Choi, I

    2015-07-01

    Despite broad medical application, induction of artificial hypometabolism in vitro and its biochemical consequence have been rarely addressed. This study aimed to elucidate whether 3-iodothyronamine (T1AM) induces hypometabolism in an in vitro model with activation of AMP-activated protein kinase (AMPK) and whether it leads to a switch in primary fuel from carbohydrates to lipids as observed in in vivo models. Mouse C2C12 myotube and T1AM, a natural derivative of thyroid hormone, were used in this study. The oxygen consumption rate (OCR) decreased in a dose-dependent manner in response to 0-100 μM T1AM for up to 10 h. Upon 6-h of exposure to 75 μM T1AM, the OCR was reduced to 60 vs. ~ 95% for the control. The intracellular [AMP]/[ATP] was 1.35-fold higher in T1AM-treated cells. RT-PCR and immunoblotting analyses revealed that treated cells had upregulated p-AMPK/AMPK (1.8-fold), carnitine palmitoyl transferase 1 mRNA, and pyruvate dehydrogenase kinase, and downregulated acetyl CoA carboxylase (0.4-fold) and pyruvate dehydrogenase phosphatase. The treated cells had darker periodic acid-Schiff staining with 1.2-fold greater glycogen content than controls. Taken together, the hypometabolic response of myotubes to T1AM was dramatic and accompanied by increases in both the relative abundance of AMP and AMPK activation, and fuel choice favoring lipids over carbohydrates. These results are consistent with the general trends observed for rodent models and true hibernators. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

    Directory of Open Access Journals (Sweden)

    Brody LP

    2017-09-01

    Full Text Available Leigh P Brody,1,* Meliz Sahuri-Arisoylu,1,* James R Parkinson,1 Harry G Parkes,2 Po Wah So,3 Nabil Hajji,4 E Louise Thomas,1 Gary S Frost,5 Andrew D Miller,6,* Jimmy D Bell1,* 1Department of Life Sciences, Faculty of Science and Technology, University of Westminster, 2CR-UK Clinical MR Research Group, Institute of Cancer Research, Sutton, Surrey, 3Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 4Department of Medicine, Division of Experimental Medicine, Centre for Pharmacology & Therapeutics, Toxicology Unit, Imperial College London, 5Faculty of Medicine, Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6Institute of Pharmaceutical Science, King’s College London, London, UK *These authors contributed equally to this work Abstract: Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA-encapsulated lipid-based delivery system – liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN. We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo. Keywords: lipid-based nanoparticles, liposomes

  16. Pathway markers for pro-resolving lipid mediators in maternal and umbilical cord blood: A Secondary analysis of the Mothers, Omega-3, & Mental Health Study

    Directory of Open Access Journals (Sweden)

    Ellen L Mozurkewich

    2016-09-01

    Full Text Available The omega-3 fatty acids docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA are precursors to immune regulatory and specialized pro-resolving mediators (SPM of inflammation termed resolvins, maresins, and protections. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5-lipoxygenase (LOX and 15-LOX metabolic pathway precursors and downstream metabolites: We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and Mental Health study to determine whether SPM and SPM precursors are augmented by dietary EPA- and DHA-rich fish oil supplementation compared to soy oil placebo. We also aimed to study whether SPM and their precursors differ in early and late pregnancy or between maternal and umbilical cord blood. We found that compared to placebo supplementation, EPA- and DHA- rich fish oil supplementation increased SPM precursor 17-HDHA concentrations in maternal and umbilical cord blood (P=0.02 We found that the D-series resolvin pathway marker 17-HDHA increased significantly between enrollment and late pregnancy (P=0.049. Levels of both 14-HDHA, a maresin pathway marker, and 17-HDHA were significantly greater in umbilical cord blood than in maternal blood (P<0.001, both.

  17. Glucagon Decreases IGF-1 Bioactivity in Humans, Independently of Insulin, by Modulating Its Binding Proteins.

    Science.gov (United States)

    Sarem, Zeinab; Bumke-Vogt, Christiane; Mahmoud, Ayman M; Assefa, Biruhalem; Weickert, Martin O; Adamidou, Aikatarini; Bähr, Volker; Frystyk, Jan; Möhlig, Matthias; Spranger, Joachim; Lieske, Stefanie; Birkenfeld, Andreas L; Pfeiffer, Andreas F H; Arafat, Ayman M

    2017-09-01

    Depending on its lipolytic activity, glucagon plays a promising role in obesity treatment. Glucagon-induced growth hormone (GH) release can promote its effect on lipid metabolism, although the underlying mechanisms have not been well-defined. The present study highlights the glucagon effect on the GH/insulinlike growth factor 1 (IGF-1)/IGF-binding protein (IGFBP) axis in vivo and in vitro, taking into consideration insulin as a confounding factor. In a double-blind, placebo-controlled study, we investigated changes in GH, IGFBP, and IGF-1 bioactivity after intramuscular glucagon administration in 13 lean controls, 11 obese participants, and 13 patients with type 1 diabetes mellitus (T1DM). The effect of glucagon on the transcription factor forkhead box protein O1 (FOXO1) translocation, the transcription of GH/IGF-1 system members, and phosphorylation of protein kinase B (Akt) was further investigated in vitro. Despite unchanged total IGF-1 and IGFBP-3 levels, glucagon decreased IGF-1 bioactivity in all study groups by increasing IGFBP-1 and IGFBP-2. The reduction in IGF-1 bioactivity occurred before the glucagon-induced surge in GH. In contrast to the transient increase in circulating insulin in obese and lean participants, no change was observed in those with T1DM. In vitro, glucagon dose dependently induced a substantial nuclear translocation of FOXO1 in human osteosarcoma cells and tended to increase IGFBP-1 and IGFBP-2 gene expression in mouse primary hepatocytes, despite absent Akt phosphorylation. Our data point to the glucagon-induced decrease in bioactive IGF-1 levels as a mechanism through which glucagon induces GH secretion. This insulin-independent reduction is related to increased IGFBP-1 and IGFBP-2 levels, which are most likely mediated via activation of the FOXO/mTOR (mechanistic target of rapamycin) pathway. Copyright © 2017 Endocrine Society

  18. Nanotech: propensity in foods and bioactives.

    Science.gov (United States)

    Kuan, Chiu-Yin; Yee-Fung, Wai; Yuen, Kah-Hay; Liong, Min-Tze

    2012-01-01

    Nanotechnology is seeing higher propensity in various industries, including food and bioactives. New nanomaterials are constantly being developed from both natural biodegradable polymers of plant and animal origins such as polysaccharides and derivatives, peptides and proteins, lipids and fats, and biocompatible synthetic biopolyester polymers such as polylactic acid (PLA), polyhydroxyalkonoates (PHA), and polycaprolactone (PCL). Applications in food industries include molecular synthesis of new functional food compounds, innovative food packaging, food safety, and security monitoring. The relevance of bioactives includes targeted delivery systems with improved bioavailability using nanostructure vehicles such as association colloids, lipid based nanoencapsulator, nanoemulsions, biopolymeric nanoparticles, nanolaminates, and nanofibers. The extensive use of nanotechnology has led to the need for parallel safety assessment and regulations to protect public health and adverse effects to the environment. This review covers the use of biopolymers in the production of nanomaterials and the propensity of nanotechnology in food and bioactives. The exposure routes of nanoparticles, safety challenges, and measures undertaken to ensure optimal benefits that outweigh detriments are also discussed.

  19. Solid lipid nanoparticles carrying chemotherapeutic drug across the blood-brain barrier through insulin receptor-mediated pathway.

    Science.gov (United States)

    Kuo, Yung-Chih; Shih-Huang, Chun-Yuan

    2013-09-01

    Carmustine (BCNU)-loaded solid lipid nanoparticles (SLNs) were grafted with 83-14 monoclonal antibody (MAb) (83-14 MAb/BCNU-SLNs) and applied to the brain-targeting delivery. Human brain-microvascular endothelial cells (HBMECs) incubated with 83-14 MAb/BCNU-SLNs were stained to demonstrate the interaction between the nanocarriers and expressed insulin receptors (IRs). The results revealed that the particle size of 83-14 MAb/BCNU-SLNs decreased with an increasing weight percentage of Dynasan 114 (DYN). Storage at 4 °C for 6 weeks slightly deformed the colloidal morphology. In addition, poloxamer 407 on 83-14 MAb/BCNU-SLNs induced cytotoxicity to RAW264.7 cells and inhibited phagocytosis by RAW264.7 cells. An increase in the weight percentage of DYN from 0% to 67% slightly reduced the viability of RAW264.7 cells and promoted phagocytosis. Moreover, the transport ability of 83-14 MAb/BCNU-SLNs across the blood-brain barrier (BBB) in vitro enhanced with an increasing weight percentage of Tween 80. 83-14 MAb on MAb/BCNU-SLNs stimulated endocytosis by HBMECs via IRs and enhanced the permeability of BCNU across the BBB. 83-14 MAb/BCNU-SLNs can be a promising antitumor drug delivery system for transporting BCNU to the brain.

  20. Reorganization of Azospirillum brasilense cell membrane is mediated by lipid composition adjustment to maintain optimal fluidity during water deficit.

    Science.gov (United States)

    Cesari, A B; Paulucci, N S; Biasutti, M A; Reguera, Y B; Gallarato, L A; Kilmurray, C; Dardanelli, M S

    2016-01-01

    We study the Azospirillum brasilense tolerance to water deficit and the dynamics of adaptive process at the level of the membrane. Azospirillum brasilense was exposed to polyethylene glycol (PEG) growth and PEG shock. Tolerance, phospholipids and fatty acid (FA) composition and membrane fluidity were determined. Azospirillum brasilense was able to grow in the presence of PEG; however, its viability was reduced. Cells grown with PEG showed membrane fluidity similar to those grown without, the lipid composition was modified, increasing phosphatidylcholine and decreasing phosphatidylethanolamine amounts. The unsaturation FAs degree was reduced. The dynamics of the adaptive response revealed a decrease in fluidity 20 min after the addition of PEG, indicating that the PEG has a fluidizing effect on the hydrophobic region of the cell membrane. Fluidity returned to initial values after 60 min of PEG exposure. Azospirillum brasilense is able to perceive osmotic changes by changing the membrane fluidity. This effect is offset by changes in the composition of membrane phospholipid and FA, contributing to the homeostasis of membrane fluidity under water deficit. This knowledge can be used to develop new Azospirillum brasilense formulations showing an adapted membrane to water deficit. © 2015 The Society for Applied Microbiology.

  1. Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: Modulation of cardiac PPAR-α-mediated transcription of fatty acid metabolic genes

    International Nuclear Information System (INIS)

    Huang, Tom H.-W.; Yang Qinglin; Harada, Masaki; Uberai, Jasna; Radford, Jane; Li, George Q.; Yamahara, Johji; Roufogalis, Basil D.; Li Yuhao

    2006-01-01

    Excess cardiac triglyceride accumulation in diabetes and obesity induces lipotoxicity, which predisposes the myocytes to death. On the other hand, increased cardiac fatty acid (FA) oxidation plays a role in the development of myocardial dysfunction in diabetes. PPAR-α plays an important role in maintaining homeostasis of lipid metabolism. We have previously demonstrated that the extract from Salacia oblonga root (SOE), an Ayurvedic anti-diabetic and anti-obesity medicine, improves hyperlipidemia in Zucker diabetic fatty (ZDF) rats (a genetic model of type 2 diabetes and obesity) and possesses PPAR-α activating properties. Here we demonstrate that chronic oral administration of SOE reduces cardiac triglyceride and FA contents and decreases the Oil red O-stained area in the myocardium of ZDF rats, which parallels the effects on plasma triglyceride and FA levels. Furthermore, the treatment suppressed cardiac overexpression of both FA transporter protein-1 mRNA and protein in ZDF rats, suggesting inhibition of increased cardiac FA uptake as the basis for decreased cardiac FA levels. Additionally, the treatment also inhibited overexpression in ZDF rat heart of PPAR-α mRNA and protein and carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase mRNAs and restored the downregulated acetyl-CoA carboxylase mRNA. These results suggest that SOE inhibits cardiac FA oxidation in ZDF rats. Thus, our findings suggest that improvement by SOE of excess cardiac lipid accumulation and increased cardiac FA oxidation in diabetes and obesity occurs by reduction of cardiac FA uptake, thereby modulating cardiac PPAR-α-mediated FA metabolic gene transcription

  2. Anti-oxidative stress regulator NF-E2-related factor 2 mediates the adaptive induction of antioxidant and detoxifying enzymes by lipid peroxidation metabolite 4-hydroxynonenal

    Directory of Open Access Journals (Sweden)

    Huang Ying

    2012-11-01

    Full Text Available Abstract Background NF-E2-related factor 2 (NRF2 regulates a battery of antioxidative and phase II drug metabolizing/detoxifying genes through binding to the antioxidant response elements (ARE. NRF2-ARE signaling plays a central role in protecting cells from a wide spectrum of reactive toxic species including reactive oxygen/nitrogen species (RONS. 4-hydroxylnonenal (4-HNE is a major end product from lipid peroxidation of omega-6 polyunsaturated fatty acids (PUFA induced by oxidative stress, and it is highly reactive to nucleophilic sites in DNA and proteins, causing cytotoxicity and genotoxicity. In this study, we examined the role of NRF2 in regulating the 4-HNE induced gene expression of antioxidant and detoxifying enzymes. Results When HeLa cells were treated with 4-HNE, NRF2 rapidly transloated into the nucleus, as determined by the distribution of NRF2 tagged with the enhanced green fluorescent protein (EGFP and increased NRF2 protein in the nuclear fraction. Transcriptional activity of ARE-luciferase was significantly induced by 0.01-10 μM of 4-HNE in a dose-dependent manner, and the induction could be blocked by pretreatment with glutathione (GSH. 4-HNE induced transcriptional expression of glutathione S-transferase (GST A4, aldoketone reductase (AKR 1C1 and heme oxygenase-1 (HO-1, and the induction was attenuated by knocking down NRF2 using small interfering RNA. Conclusions NRF2 is critical in mediating 4-HNE induced expression of antioxidant and detoxifying genes. This may account for one of the major cellular defense mechanisms against reactive metabolites of lipids peroxidation induced by oxidative stress and protect cells from cytotoxicity.

  3. High content analysis platform for optimization of lipid mediated CRISPR-Cas9 delivery strategies in human cells.

    Science.gov (United States)

    Steyer, Benjamin; Carlson-Stevermer, Jared; Angenent-Mari, Nicolas; Khalil, Andrew; Harkness, Ty; Saha, Krishanu

    2016-04-01

    Non-viral gene-editing of human cells using the CRISPR-Cas9 system requires optimized delivery of multiple components. Both the Cas9 endonuclease and a single guide RNA, that defines the genomic target, need to be present and co-localized within the nucleus for efficient gene-editing to occur. This work describes a new high-throughput screening platform for the optimization of CRISPR-Cas9 delivery strategies. By exploiting high content image analysis and microcontact printed plates, multi-parametric gene-editing outcome data from hundreds to thousands of isolated cell populations can be screened simultaneously. Employing this platform, we systematically screened four commercially available cationic lipid transfection materials with a range of RNAs encoding the CRISPR-Cas9 system. Analysis of Cas9 expression and editing of a fluorescent mCherry reporter transgene within human embryonic kidney cells was monitored over several days after transfection. Design of experiments analysis enabled rigorous evaluation of delivery materials and RNA concentration conditions. The results of this analysis indicated that the concentration and identity of transfection material have significantly greater effect on gene-editing than ratio or total amount of RNA. Cell subpopulation analysis on microcontact printed plates, further revealed that low cell number and high Cas9 expression, 24h after CRISPR-Cas9 delivery, were strong predictors of gene-editing outcomes. These results suggest design principles for the development of materials and transfection strategies with lipid-based materials. This platform could be applied to rapidly optimize materials for gene-editing in a variety of cell/tissue types in order to advance genomic medicine, regenerative biology and drug discovery. CRISPR-Cas9 is a new gene-editing technology for "genome surgery" that is anticipated to treat genetic diseases. This technology uses multiple components of the Cas9 system to cut out disease-causing mutations

  4. Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity

    Directory of Open Access Journals (Sweden)

    T.I. Omotayo

    2015-04-01

    Full Text Available The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe2+-mediated in vitro oxidative stress model. The results show that Fe2+ inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe2+ inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe2+ may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe2+ and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.

  5. TALEN- and CRISPR/Cas9-Mediated Gene Editing in Human Pluripotent Stem Cells Using Lipid-Based Transfection.

    Science.gov (United States)

    Hendriks, William T; Jiang, Xin; Daheron, Laurence; Cowan, Chad A

    2015-08-03

    Using custom-engineered nuclease-mediated genome editing, such as Transcription Activator-Like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) RNA-guided Cas9 nucleases, human pluripotent stem cell (hPSC) lines with knockout or mutant alleles can be generated and differentiated into various cell types. This strategy of genome engineering in hPSCs will prove invaluable for studying human biology and disease. Here, we provide a detailed protocol for design and construction of TALEN and CRISPR vectors, testing of their nuclease activity, and delivery of TALEN or CRISPR vectors into hPSCs. In addition, we describe the use of single-stranded oligodeoxynucleotides (ssODNs) to introduce or repair point mutations. Next, we describe the identification of edited hPSC clones without antibiotic selection, including their clonal selection, genotyping, and expansion for downstream applications. Copyright © 2015 John Wiley & Sons, Inc.

  6. Perilipin-mediated lipid droplet formation in adipocytes promotes sterol regulatory element-binding protein-1 processing and triacylglyceride accumulation.

    Directory of Open Access Journals (Sweden)

    Yu Takahashi

    Full Text Available Sterol regulatory element-binding protein-1 (SREBP-1 has been thought to be a critical factor that assists adipogenesis. During adipogenesis SREBP-1 stimulates lipogenic gene expression, and peroxisome proliferator-activated receptor γ (PPARγ enhances perilipin (plin gene expression, resulting in generating lipid droplets (LDs to store triacylglycerol (TAG in adipocytes. Plin coats adipocyte LDs and protects them from lipolysis. Here we show in white adipose tissue (WAT of plin-/- mice that nuclear active SREBP-1 and its target gene expression, but not nuclear SREBP-2, significantly decreased on attenuated LD formation. When plin-/- mouse embryonic fibroblasts (MEFs differentiated into adipocytes, attenuated LDs were formed and nuclear SREBP-1 decreased, but enforced plin expression restored them to their original state. Since LDs are largely derived from the endoplasmic reticulum (ER, alterations in the ER cholesterol content were investigated during adipogenesis of 3T3-L1 cells. The ER cholesterol greatly reduced in differentiated adipocytes. The ER cholesterol level in plin-/- WAT was significantly higher than that of wild-type mice, suggesting that increased LD formation caused a change in ER environment along with a decrease in cholesterol. When GFP-SREBP-1 fusion proteins were exogenously expressed in 3T3-L1 cells, a mutant protein lacking the S1P cleavage site was poorly processed during adipogenesis, providing evidence of the increased canonical pathway for SREBP processing in which SREBP-1 is activated by two cleavage enzymes in the Golgi. Therefore, LD biogenesis may create the ER microenvironment favorable for SREBP-1 activation. We describe the novel interplay between LD formation and SREBP-1 activation through a positive feedback loop.

  7. Inhibition by TNF-alpha and IL-4 of cationic lipid mediated gene transfer in cystic fibrosis tracheal gland cells.

    Science.gov (United States)

    Bastonero, Sonia; Gargouri, Myriem; Ortiou, Sandrine; Guéant, Jean-Louis; Merten, Marc D

    2005-11-01

    In vivo, tracheal gland serous cells highly express the cystic fibrosis transmembrane conductance regulator (cftr) gene. This gene is mutated in the lethal monogenic disease cystic fibrosis (CF). Clinical trials in which the human CFTR cDNA was delivered to the respiratory epithelia of CF patients have resulted in weak and transient gene expression. As CF is characterized by mucus inspissation, airway infection, and severe inflammation, we tested the hypothesis that inflammation and especially two cytokines involved in the Th1/Th2 inflammatory response, interleukin 4 (IL-4) and TNFalpha, could inhibit gene transfer efficiency using a model of human CF tracheal gland cells (CF-KM4) and Lipofectamine reagent as a transfection reagent. The specific secretory defects of CF-KM4 cells were corrected by Lipofectamine-mediated human CFTR gene transfer. However, this was altered when cells were pre-treated with IL-4 and TNFalpha. Inhibition of luciferase reporter gene expression by IL-4 and TNFalpha pre-treated CF-KM4 cells was measured by activity and real-time RT-PCR. Both cytokines induced similar and synergistic inhibition of transgene expression and activity. This cytokine-mediated inhibition could be prevented by anti-inflammatory agents such as glucocorticoids but not by non-steroidal (NSAI) agents. This data suggests that an inflammatory context generated by IL-4 and TNFalpha can inhibit human CFTR gene transfer in CF tracheal gland cells and that glucocorticoids may have a protecting action. Copyright (c) 2005 John Wiley & Sons, Ltd.

  8. Sorafenib suppresses TGF-β responses by inducing caveolae/lipid raft-mediated internalization/degradation of cell-surface type II TGF-β receptors: Implications in development of effective adjunctive therapy for hepatocellular carcinoma.

    Science.gov (United States)

    Chung, Chih-Ling; Wang, Shih-Wei; Sun, Wei-Chih; Shu, Chih-Wen; Kao, Yu-Chen; Shiao, Meng-Shin; Chen, Chun-Lin

    2018-04-18

    Sorafenib is the only FDA approved drug for the treatment of advanced hepatocellular carcinoma (HCC) and other malignancies. Studies indicate that TGF-β signalling is associated with tumour progression in HCC. Autocrine and paracrine TGF-β promotes tumour growth and malignancy by inducing epithelial-mesenchymal transition (EMT). Sorafenib is believed to antagonize tumour progression by inhibiting TGF-β-induced EMT. It improves survival of patients but HCC later develops resistance and relapses. The underlying mechanism of resistance is unknown. Understanding of the molecular mechanism of sorafenib inhibition of TGF-β-induced signalling or responses in HCC may lead to development of adjunctive effective therapy for HCC. In this study, we demonstrate that sorafenib suppresses TGF-β responsiveness in hepatoma cells, hepatocytes, and animal liver, mainly by downregulating cell-surface type II TGF-β receptors (TβRII) localized in caveolae/lipid rafts and non-lipid raft microdomains via caveolae/lipid rafts-mediated internalization and degradation. Furthermore, sorafenib-induced downregulation and degradation of cell-surface TβRII is prevented by simultaneous treatment with a caveolae disruptor or lysosomal inhibitors. On the other hand, sorafenib only downregulates cell-surface TβRII localized in caveolae/lipid rafts but not localized in non-lipid raft microdomains in hepatic stellate cells. These results suggest that sorafenib inhibits TGF-β signalling mainly by inducing caveolae/lipid raft-mediated internalization and degradation of cell-surface TβR-II in target cells. They may also imply that treatment with agents which promote formation of caveolae/lipid rafts, TGF-β receptor kinase inhibitors (e.g., LY2157299) or TGF-β peptide antagonists (by liver-targeting delivery) may be considered as effective adjunct therapy with sorafenib for HCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Functional and in vitro gastric digestibility of the whey protein hydrogel loaded with nanostructured lipid carriers and gelled via citric acid-mediated crosslinking.

    Science.gov (United States)

    Hashemi, Behnaz; Madadlou, Ashkan; Salami, Maryam

    2017-12-15

    Nanostructured lipid carriers (NLCs) with mean size of 347nm were fabricated and added into a heat-denatured whey protein solution. The subsequent crosslinking of proteins by citric acid or CaCl 2 resulted in the formation of cold-set hydrogels. Fourier transform infrared spectroscopy (FTIR) proposed formation of more hydrogen bonds in gel due to NLC loading or citric acid-mediated gelation. It was also found based on FITR spectroscopy that citric acid crosslinking disordered whey proteins. Scanning electron microscopy (SEM) imaging showed a non-porous and finely meshed microstructure for the crosslinked gels compared to non-crosslinked counterparts. Crosslinking also increased the firmness and water-holding capacity of gels. In pepsin-free fluid, a strong correlation existed between reduction in gel swellability and digestibility over periods up to 60min due to NLC loading and citric acid gelation. However, in peptic fluid, NLC loading and citric acid crosslinking brought about much higher decrease in digestibility than swellability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Lipid raft-mediated miR-3908 inhibition of migration of breast cancer cell line MCF-7 by regulating the interactions between AdipoR1 and Flotillin-1.

    Science.gov (United States)

    Li, Yuan; Shan, Fei; Chen, Jinglong

    2017-03-21

    The mechanisms of lipid raft regulation by microRNAs in breast cancer are not fully understood. This work focused on the evaluation and identification of miR-3908, which may be a potential biomarker related to the migration of breast cancer cells, and elucidates lipid-raft-regulating cell migration in breast cancer. To confirm the prediction that miR-3908 is matched with AdipoR1, we used 3'-UTR luciferase activity of AdipoR1 to assess this. Then, human breast cancer cell line MCF-7 was cultured in the absence or presence of the mimics or inhibitors of miR-3908, after which the biological functions of MCF-7 cells were analyzed. The protein expression of AdipoR1, AMPK, and SIRT-1 were examined. The interaction between AdipoR1 and Flotillin-1, or its effects on lipid rafts on regulating cell migration of MCF-7, was also investigated. AdipoR1 is a direct target of miR-3908. miR-3908 suppresses the expression of AdipoR1 and its downstream pathway genes, including AMPK, p-AMPK, and SIRT-1. miR-3908 enhances the process of breast cancer cell clonogenicity. miR-3908 exerts its effects on the proliferation and migration of MCF-7 cells, which are mediated by lipid rafts regulating AdipoR1's ability to bind Flotillin-1. miR-3908 is a crucial mediator of the migration process in breast cancer cells. Lipid rafts regulate the interactions between AdipoR1 and Flotillin-1 and then the migration process associated with miR-3908 in MCF-7 cells. Our findings suggest that targeting miR-3908 and the lipid raft, may be a promising strategy for the treatment and prevention of breast cancer.

  11. Effects of parenteral infusion with medium-chain triglycerides and safflower oil emulsions on hepatic lipids, plasma amino acids and inflammatory mediators in septic rats.

    Science.gov (United States)

    Yeh, S; Chao, C; Lin, M; Chen, W

    2000-04-01

    This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using medium-chain triglycerides (MCT) versus safflower oil (SO) emulsion as fat sources on hepatic lipids, plasma amino acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were divided into two groups and received TPN. TPN provided 300kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or a mixture of MCT and soybean oil (9:1) (MO). After receiving TPN for 6 days, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture, whereas control rats received sham operation. All rats were classified into four groups as follows: MCT control group (MOC, n= 8), MCT sepsis group (MOS, n= 8), safflower oil control group (SOC, n= 8), and safflower oil sepsis group (SOS, n= 11). The results of the study demonstrated that the MOS group had lower hepatic lipids than did the SOS group. Plasma leucine and isoleucine levels were significantly lower in the SOS than in the SOC group, but no differences in these two amino acids were observed between the MOC and MOS groups. Plasma arginine levels were significantly lower in septic groups than in those without sepsis despite whether MCT or safflower oil was infused. Plasma glutamine and alanine levels, however, did not differ between septic and non-septic groups either in the SO or MO groups. No differences in interleukin-1b, interleukin-6, tumor necrosis factor-alpha, and leukotriene B(4)concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction is septic rats preinfused MCT is not as obvious as those preinfused safflower oil. Compared with safflower oil, TPN with MCT administration has better effects on

  12. Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.

    Science.gov (United States)

    Morel, Etienne; Ghezzal, Sara; Lucchi, Géraldine; Truntzer, Caroline; Pais de Barros, Jean-Paul; Simon-Plas, Françoise; Demignot, Sylvie; Mineo, Chieko; Shaul, Philip W; Leturque, Armelle; Rousset, Monique; Carrière, Véronique

    2018-02-01

    Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Bioactive polymeric scaffolds for tissue engineering

    Directory of Open Access Journals (Sweden)

    Scott Stratton

    2016-12-01

    Full Text Available A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

  14. Single histidine residue in head-group region is sufficient to impart remarkable gene transfection properties to cationic lipids: evidence for histidine-mediated membrane fusion at acidic pH.

    Science.gov (United States)

    Kumar, V V; Pichon, C; Refregiers, M; Guerin, B; Midoux, P; Chaudhuri, A

    2003-08-01

    Presence of endosome-disrupting multiple histidine functionalities in the molecular architecture of cationic polymers, such as polylysine, has previously been demonstrated to significantly enhance their in vitro gene delivery efficiencies. Towards harnessing improved transfection property through covalent grafting of endosome-disrupting single histidine functionality in the molecular structure of cationic lipids, herein, we report on the design, the synthesis and the transfection efficiency of two novel nonglycerol-based histidylated cationic amphiphiles. We found that L-histidine-(N,N-di-n-hexadecylamine)ethylamide (lipid 1) and L-histidine-(N,N-di-n-hexadecylamine,-N-methyl)ethylamide (lipid 2) in combination with cholesterol gave efficient transfections into various cell lines. The transfection efficiency of Chol/lipid 1 lipoplexes into HepG2 cells was two order of magnitude higher than that of FuGENE(TM)6 and DC-Chol lipoplexes, whereas it was similar into A549, 293T7 and HeLa cells. A better efficiency was obtained with Chol/lipid 2 lipoplexes when using the cytosolic luciferase expression vector (pT7Luc) under the control of the bacterial T7 promoter. Membrane fusion activity measurements using fluorescence resonance energy transfer (FRET) technique showed that the histidine head-groups of Chol/lipid 1 liposomes mediated membrane fusion in the pH range 5-7. In addition, the transgene expression results using the T7Luc expression vector convincingly support the endosome-disrupting role of the presently described mono-histidylated cationic transfection lipids and the release of DNA into the cytosol. We conclude that covalent grafting of a single histidine amino acid residue to suitable twin-chain hydrophobic compounds is able to impart remarkable transfection properties on the resulting mono-histidylated cationic amphiphile, presumably via the endosome-disrupting characteristics of the histidine functionalities.

  15. Dietary fish protein hydrolysates containing bioactive motifs affect serum and adipose tissue fatty acid compositions, serum lipids, postprandial glucose regulation and growth in obese Zucker fa/fa rats.

    Science.gov (United States)

    Drotningsvik, Aslaug; Mjøs, Svein A; Pampanin, Daniela M; Slizyte, Rasa; Carvajal, Ana; Remman, Tore; Høgøy, Ingmar; Gudbrandsen, Oddrun A

    2016-10-01

    The world's fisheries and aquaculture industries produce vast amounts of protein-containing by-products that can be enzymatically hydrolysed to smaller peptides and possibly be used as additives to functional foods and nutraceuticals targeted for patients with obesity-related metabolic disorders. To investigate the effects of fish protein hydrolysates on markers of metabolic disorders, obese Zucker fa/fa rats consumed diets with 75 % of protein from casein/whey (CAS) and 25 % from herring (HER) or salmon (SAL) protein hydrolysate from rest raw material, or 100 % protein from CAS for 4 weeks. The fatty acid compositions were similar in the experimental diets, and none of them contained any long-chain n-3 PUFA. Ratios of lysine:arginine and methionine:glycine were lower in HER and SAL diets when compared with CAS, and taurine was detected only in fish protein hydrolysate diets. Motifs with reported hypocholesterolemic or antidiabetic activities were identified in both fish protein hydrolysates. Rats fed HER diet had lower serum HDL-cholesterol and LDL-cholesterol, and higher serum TAG, MUFA and n-3:n-6 PUFA ratio compared with CAS-fed rats. SAL rats gained more weight and had better postprandial glucose regulation compared with CAS rats. Serum lipids and fatty acids were only marginally affected by SAL, but adipose tissue contained less total SFA and more total n-3 PUFA when compared with CAS. To conclude, diets containing hydrolysed rest raw material from herring or salmon proteins may affect growth, lipid metabolism, postprandial glucose regulation and fatty acid composition in serum and adipose tissue in obese Zucker rats.

  16. Development of bioactive materials for glioblastoma therapy

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2016-09-01

    Full Text Available Glioblastoma is the most common and deadly human brain cancers. Unique barriers hinder the drug delivering pathway due to the individual position of glioblastoma, including blood-brain barrier and blood-brain tumor barrier. Numerous bioactive materials have been exploited and applied as the transvascular delivery carriers of therapeutic drugs. They promote site-specific accumulation and long term release of the encapsulated drugs at the tumor sites and reduce side effects with systemic delivery. And the delivery systems exhibit a certain extent of anti-glioblastoma effect and extend the median survival time. However, few of them step into the clinical trials. In this review, we will investigate the recent studies of bioactive materials for glioblastoma chemotherapy, including the inorganic materials, lipids and polymers. These bioactive materials construct diverse delivery vehicles to trigger tumor sites in brain intravenously. Herein, we exploit their functionality in drug delivery and discuss the deficiency for the featured tumors, to provide guidance for establishing optimized therapeutic drug formulation for anti-glioblastoma therapy and pave the way for clinical application.

  17. Mechanistic Study of the sPLA2 Mediated Hydrolysis of a Thio-ester Pro Anticancer Ether Lipid

    DEFF Research Database (Denmark)

    Linderoth, Lars; Fristrup, Peter; Hansen, Martin

    2009-01-01

    Secretory phospholipase A2 (sPLA2) is an interesting enzyme for triggered liposomal drug delivery to tumor tissue due the overexpression of sPLA2 in cancerous tissue. A drug delivery system based on the triggered release of therapeutics from sPLA2-sensitive liposomes constituted of pro anticancer...... ether lipids, which become cytotoxic upon sPLA2-catalyzed hydrolysis has previously been established. To optimize the hydrolysis rate of the lipids and thereby optimizing the release profile of the drugs from the liposomes, we have synthesized a thio-ester pro anticancer ether lipid. Liposomes...... constituted of this lipid showed an altered rate of hydrolysis by sPLA2. We have tested the cytotoxicity of the thio-ester pro anticancer ether lipids toward cancer cells, and the results showed that the cytotoxicity is indeed maintained upon sPLA2 exposure. To further understand the origin for the observed...

  18. Effects of co-medicated drugs on cyclophosphamide bioactivation in human liver microsomes

    NARCIS (Netherlands)

    de Jonge, Milly E.; Huitema, Alwin D. R.; van Dam, Selma M.; Rodenhuis, Sjoerd; Beijnen, Jos H.

    2005-01-01

    The alkylating agent cyclophosphamide (CP) is a prodrug requiring cytochrome P-450-mediated bioactivation to form the active 4-hydroxycyclophosphamide (4OHCP). Modifications in the rate of CP bioactivation may have implications for the effectiveness of CP therapy, especially in high-dose regimens.

  19. Applied bioactive polymeric materials

    CERN Document Server

    Carraher, Charles; Foster, Van

    1988-01-01

    The biological and biomedical applications of polymeric materials have increased greatly in the past few years. This book will detail some, but not all, of these recent developments. There would not be enough space in this book to cover, even lightly, all of the major advances that have occurred. Some earlier books and summaries are available by two of this book's Editors (Gebelein & Carraher) and these should be consul ted for additional information. The books are: "Bioactive Polymeric Systems" (Plenum, 1985); "Polymeric Materials In Medication" (Plenum, 1985); "Biological Acti vi ties of Polymers" (American Chemical Society, 1982). Of these three, "Bioacti ve Polymeric Systems" should be the most useful to a person who is new to this field because it only contains review articles written at an introductory level. The present book primarily consists of recent research results and applications, with only a few review or summary articles. Bioactive polymeric materials have existed from the creation of life...

  20. Bioactive technologies for hemocompatibility.

    Science.gov (United States)

    Tanzi, Maria Cristina

    2005-07-01

    The contact of any biomaterial with blood gives rise to multiple pathophysiologic defensive mechanisms such as activation of the coagulation cascade, platelet adhesion and activation of the complement system and leukocytes. The reduction of these events is of crucial importance for the successful clinical performance of a cardiovascular device. This can be achieved by improving the hemocompatibility of the device materials or by pharmacologic inhibition of the key enzymes responsible for the activation of the cascade reactions, or a combination of both. Different strategies have been developed during the last 20 years, and this article attempts to review the most significant, by dividing them into three main categories: bioinert or biopassive, biomimetic and bioactive strategies. With regard to bioactive strategies, particular attention is given to heparin immobilization and recent related technologies. References from both scientific literature and commercial sites are provided. Future development and studies are suggested.

  1. The Anti-Inflammatory Effect of Algae-Derived Lipid Extracts on Lipopolysaccharide (LPS)-Stimulated Human THP-1 Macrophages.

    Science.gov (United States)

    Robertson, Ruairi C; Guihéneuf, Freddy; Bahar, Bojlul; Schmid, Matthias; Stengel, Dagmar B; Fitzgerald, Gerald F; Ross, R Paul; Stanton, Catherine

    2015-08-20

    Algae contain a number of anti-inflammatory bioactive compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA) and chlorophyll a, hence as dietary ingredients, their extracts may be effective in chronic inflammation-linked metabolic diseases such as cardiovascular disease. In this study, anti-inflammatory potential of lipid extracts from three red seaweeds (Porphyra dioica, Palmaria palmata and Chondrus crispus) and one microalga (Pavlova lutheri) were assessed in lipopolysaccharide (LPS)-stimulated human THP-1 macrophages. Extracts contained 34%-42% total fatty acids as n-3 PUFA and 5%-7% crude extract as pigments, including chlorophyll a, β-carotene and fucoxanthin. Pretreatment of the THP-1 cells with lipid extract from P. palmata inhibited production of the pro-inflammatory cytokines interleukin (IL)-6 (p lipid extracts. The lipid extracts effectively inhibited the LPS-induced pro-inflammatory signaling pathways mediated via toll-like receptors, chemokines and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling molecules. These results suggest that lipid extracts from P. lutheri, P. palmata, P. dioica and C. crispus can inhibit LPS-induced inflammatory pathways in human macrophages. Therefore, algal lipid extracts should be further explored as anti-inflammatory ingredients for chronic inflammation-linked metabolic diseases.

  2. Bioactive glass in tissue engineering

    Science.gov (United States)

    Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

    2011-01-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  3. Broad spectrum bioactive sunscreens.

    Science.gov (United States)

    Velasco, Maria Valéria Robles; Sarruf, Fernanda Daud; Salgado-Santos, Idalina Maria Nunes; Haroutiounian-Filho, Carlos Alberto; Kaneko, Telma Mary; Baby, André Rolim

    2008-11-03

    The development of sunscreens containing reduced concentration of chemical UV filters, even though, possessing broad spectrum effectiveness with the use of natural raw materials that improve and infer UV absorption is of great interest. Due to the structural similarities between polyphenolic compounds and organic UV filters, they might exert photoprotection activity. The objective of the present research work was to develop bioactive sunscreen delivery systems containing rutin, Passiflora incarnata L. and Plantago lanceolata extracts associated or not with organic and inorganic UV filters. UV transmission of the sunscreen delivery system films was performed by using diffuse transmittance measurements coupling to an integrating sphere. In vitro photoprotection efficacy was evaluated according to the following parameters: estimated sun protection factor (SPF); Boot's Star Rating category; UVA/UVB ratio; and critical wavelength (lambda(c)). Sunscreen delivery systems obtained SPF values ranging from 0.972+/-0.004 to 28.064+/-2.429 and bioactive compounds interacted with the UV filters positive and negatively. This behavior may be attributed to: the composition of the delivery system; the presence of inorganic UV filter and quantitative composition of the organic UV filters; and the phytochemical composition of the P. incarnata L. and P. lanceolata extracts. Among all associations of bioactive compounds and UV filters, we found that the broad spectrum sunscreen was accomplished when 1.68% (w/w) P. incarnata L. dry extract was in the presence of 7.0% (w/w) ethylhexyl methoxycinnamate, 2.0% (w/w) benzophenone-3 and 2.0% (w/w) TiO(2). It was demonstrated that this association generated estimated SPF of 20.072+/-0.906 and it has improved the protective defense against UVA radiation accompanying augmentation of the UVA/UVB ratio from 0.49 to 0.52 and lambda(c) from 364 to 368.6nm.

  4. Electrodiffusion of Lipids on Membrane Surfaces

    OpenAIRE

    Zhou, Y. C.

    2011-01-01

    Random lateral translocation of lipids and proteins is a universal process on membrane surfaces. Local aggregation or organization of lipids and proteins can be induced when this lateral random diffusion is mediated by the electrostatic interactions and membrane curvature. Though the lateral diffusion rates of lipids on membrane of various compositions are measured and the electrostatic free energies of predetermined protein-membrane-lipid systems can be computed, the process of the aggregati...

  5. Omega-3 fatty acids promote fatty acid utilization and production of pro-resolving lipid mediators in alternatively activated adipose tissue macrophages.

    Science.gov (United States)

    Rombaldova, Martina; Janovska, Petra; Kopecky, Jan; Kuda, Ondrej

    2017-08-26

    It is becoming increasingly apparent that mutual interactions between adipocytes and immune cells are key to the integrated control of adipose tissue inflammation and lipid metabolism in obesity, but little is known about the non-inflammatory functions of adipose tissue macrophages (ATMs) and how they might be impacted by neighboring adipocytes. In the current study we used metabolipidomic analysis to examine the adaptations to lipid overload of M1 or M2 polarized macrophages co-incubated with adipocytes and explored potential benefits of omega-3 polyunsaturated fatty acids (PUFA). Macrophages adjust their metabolism to process excess lipids and M2 macrophages in turn modulate lipolysis and fatty acids (FA) re-esterification of adipocytes. While M1 macrophages tend to store surplus FA as triacylglycerols and cholesteryl esters in lipid droplets, M2 macrophages channel FA toward re-esterification and β-oxidation. Dietary omega-3 PUFA enhance β-oxidation in both M1 and M2. Our data document that ATMs contribute to lipid trafficking in adipose tissue and that omega-3 PUFA could modulate FA metabolism of ATMs. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Lipid somersaults

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Menon, Anant K.

    2016-01-01

    Membrane lipids diffuse rapidly in the plane of the membrane but their ability to flip spontaneously across a membrane bilayer is hampered by a significant energy barrier. Thus spontaneous flip-flop of polar lipids across membranes is very slow, even though it must occur rapidly to support diverse...... aspects of cellular life. Here we discuss the mechanisms by which rapid flip-flop occurs, and what role lipid flipping plays in membrane homeostasis and cell growth. We focus on conceptual aspects, highlighting mechanistic insights from biochemical and in silico experiments, and the recent, ground......-breaking identification of a number of lipid scramblases....

  7. Bioactive substances of the Techirghiol therapeutic mud

    Directory of Open Access Journals (Sweden)

    Mihail Hoteteu

    2018-02-01

    Full Text Available The study aims to characterize Techirghiol's sapropelic mud both by determining the organic and inorganic composition of the constituent phases and by isolating some compounds of humic substances. The distribution between the solid and liquid phases of the peloid of the Ca2+, Mg2+, Fe3+cations, PO43- anion, bioactive compounds of the protein, lipid and carbohydrate classes as well as the phosphatase activity of Techirghiol sapropelic mud are analyzed. The mud is fractionated using the pH and solvent polarity variation and is spectrophotometrically characterized based on absorption in the wavelength range 340-700 nm humic acids and fulvic acids differentiated on the basis of solubility and molecular mass.

  8. Wheat IgE-mediated food allergy in European patients: alpha-amylase inhibitors, lipid transfer proteins and low-molecular-weight glutenins

    DEFF Research Database (Denmark)

    Pastorello, Elide A; Farioli, Laura; Conti, Amedeo

    2007-01-01

    for sodium dodecyl sulfate-polyacrylamide gel electrophoresis/immunoblotting of the three Osborne's protein fractions (albumin/globulin, gliadins and glutenins) of raw and cooked wheat. Thermal sensitivity of wheat lipid transfer protein (LTP) was investigated by spectroscopic approaches. IgE cross...

  9. INTERACTION OF ALDEHYDES DERIVED FROM LIPID PEROXIDATION AND MEMBRANE PROTEINS.

    Directory of Open Access Journals (Sweden)

    Stefania ePizzimenti

    2013-09-01

    Full Text Available A great variety of compounds are formed during lipid peroxidation of polyunsaturated fatty acids of membrane phospholipids. Among them, bioactive aldehydes, such as 4-hydroxyalkenals, malondialdehyde (MDA and acrolein, have received particular attention since they have been considered as toxic messengers that can propagate and amplify oxidative injury. In the 4-hydroxyalkenal class, 4-hydroxy-2-nonenal (HNE is the most intensively studied aldehyde, in relation not only to its toxic function, but also to its physiological role. Indeed, HNE can be found at low concentrations in human tissues and plasma and participates in the control of biological processes, such as signal transduction, cell proliferation and differentiation. Moreover, at low doses, HNE exerts an anti-cancer effect, by inhibiting cell proliferation, angiogenesis, cell adhesion and by inducing differentiation and/or apoptosis in various tumor cell lines. It is very likely that a substantial fraction of the effects observed in cellular responses, induced by HNE and related aldehydes, be mediated by their interaction with proteins, resulting in the formation of covalent adducts or in the modulation of their expression and/or activity. In this review we focus on membrane proteins affected by lipid peroxidation-derived aldehydes, under physiological and pathological conditions.

  10. Cell-based lipid flippase assay employing fluorescent lipid derivatives

    DEFF Research Database (Denmark)

    Jensen, Maria Stumph; Costa, Sara; Günther-Pomorski, Thomas

    2016-01-01

    P-type ATPases in the P4 subfamily (P4-ATPases) are transmembrane proteins unique for eukaryotes that act as lipid flippases, i.e., to translocate phospholipids from the exofacial to the cytofacial monolayer of cellular membranes. While initially characterized as aminophospholipid translocases, s...... flippase activities in the plasma membrane of cells, using yeast as an example.......P-type ATPases in the P4 subfamily (P4-ATPases) are transmembrane proteins unique for eukaryotes that act as lipid flippases, i.e., to translocate phospholipids from the exofacial to the cytofacial monolayer of cellular membranes. While initially characterized as aminophospholipid translocases......, studies of individual P4-ATPase family members from fungi, plants, and animals show that P4-ATPases differ in their substrate specificities and mediate transport of a broader range of lipid substrates. Here, we describe an assay based on fluorescent lipid derivatives to monitor and characterize lipid...

  11. The process of lipid storage in insect oocytes: The involvement of β-chain of ATP synthase in lipophorin-mediated lipid transfer in the chagas' disease vector Panstrongylus megistus (Hemiptera: Reduviidae).

    Science.gov (United States)

    Fruttero, Leonardo L; Leyria, Jimena; Ramos, Fabián O; Stariolo, Raúl; Settembrini, Beatriz P; Canavoso, Lilián E

    2017-01-01

    Lipophorin is the main lipoprotein in the hemolymph of insects. During vitellogenesis, lipophorin delivers its hydrophobic cargo to developing oocytes by its binding to non-endocytic receptors at the plasma membrane of the cells. In some species however, lipophorin may also be internalized to some extent, thus maximizing the storage of lipid resources in growing oocytes. The ectopic β chain of ATP synthase (β-ATPase) was recently described as a putative non-endocytic lipophorin receptor in the anterior midgut of the hematophagous insect Panstrongylus megistus. In the present work, females of this species at the vitellogenic stage of the reproductive cycle were employed to investigate the role of β-ATPase in the transfer of lipids to the ovarian tissue. Subcellular fractionation and western blot revealed the presence of β-ATPase in the microsomal membranes of the ovarian tissue, suggesting its localization in the plasma membrane. Immunofluorescence assays showed partial co-localization of β-ATPase and lipophorin in the membrane of oocytes as well as in the basal domain of the follicular epithelial cells. Ligand blotting and co-immunoprecipitation approaches confirmed the interaction between lipophorin and β-ATPase. In vivo experiments with an anti-β-ATPase antibody injected to block such an interaction demonstrated that the antibody significantly impaired the transfer of fatty acids from lipophorin to the oocyte. However, the endocytic pathway of lipophorin was not affected. On the other hand, partial inhibition of ATP synthase activity did not modify the transfer of lipids from lipophorin to oocytes. When the assays were performed at 4°C to diminish endocytosis, the results showed that the antibody interfered with lipophorin binding to the oocyte plasma membrane as well as with the transfer of fatty acids from the lipoprotein to the oocyte. The findings strongly support that β-ATPase plays a role as a docking lipophorin receptor at the ovary of P. megistus

  12. Sources and Bioactive Properties of Conjugated Dietary Fatty Acids.

    Science.gov (United States)

    Hennessy, Alan A; Ross, Paul R; Fitzgerald, Gerald F; Stanton, Catherine

    2016-04-01

    The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.

  13. Therapeutic potential of dairy bioactive peptides: A contemporary perspective.

    Science.gov (United States)

    Sultan, Saira; Huma, Nuzhat; Butt, Masood Sadiq; Aleem, Muhammad; Abbas, Munawar

    2018-01-02

    Dairy products are associated with numerous health benefits. These are a good source of nutrients such as carbohydrates, protein (bioactive peptides), lipids, minerals, and vitamins, which are essential for growth, development, and maintenance of the human body. Accordingly, dairy bioactive peptides are one of the targeted compounds present in different dairy products. Dairy bioactive compounds can be classified as antihypertensive, anti-oxidative, immmunomodulant, anti-mutagenic, antimicrobial, opoid, anti-thrombotic, anti-obesity, and mineral-binding agents, depending upon biological functions. These bioactive peptides can easily be produced by enzymatic hydrolysis, and during fermentation and gastrointestinal digestion. For this reason, fermented dairy products, such as yogurt, cheese, and sour milk, are gaining popularity worldwide, and are considered excellent source of dairy peptides. Furthermore, fermented and non-fermented dairy products are associated with lower risks of hypertension, coagulopathy, stroke, and cancer insurgences. The current review article is an attempt to disseminate general information about dairy peptides and their health claims to scientists, allied stakeholders, and, certainly, readers.

  14. Human milk proresolving mediators stimulate resolution of acute inflammation.

    Science.gov (United States)

    Arnardottir, Hildur; Orr, Sarah K; Dalli, Jesmond; Serhan, Charles N

    2016-05-01

    Human milk contains nutrients and bioactive products relevant to infant development and immunological protection. Here, we investigated the proresolving properties of milk using human milk lipid mediator isolates (HLMIs) and determined their impact on resolution programs in vivo and with human macrophages. HLMIs reduced the maximum neutrophil numbers (14.6±1.2 × 10(6)-11.0±1.0 × 10(6) cells per exudate) and shortened the resolution interval (Ri; 50% neutrophil reduction) by 54% compared with peritonitis. Using rigorous liquid-chromatography tandem-mass spectrometry (LC-MS-MS)-based lipid mediator (LM) metabololipidomics, we demonstrated that human milk possesses a proresolving LM-specialized proresolving mediator (LM-SPM) signature profile, containing SPMs (e.g. resolvins (Rv), protectins (PDs), maresins (MaRs), and lipoxins (LXs)) at bioactive levels (pico-nanomolar concentrations) that enhanced human macrophage efferocytosis and bacterial containment. SPMs identified in human milk included D-series Rvs (e.g., RvD1, RvD2, RvD3, AT-RvD3, and RvD4), PD1, MaR1, E-series Rvs (e.g. RvE1, RvE2, and RvE3), and LXs (LXA4 and LXB4). Of the SPMs identified in human milk, RvD2 and MaR1 (50 ng per mouse) individually shortened Ri by ∼75%. Milk from mastitis gave higher leukotriene B4 and prostanoids and lower SPM levels. Taken together, these findings provide evidence that human milk has proresolving actions via comprehensive LM-SPM profiling, describing a potentially novel mechanism in maternal-infant biochemical imprinting.

  15. Bioactive glasses: Frontiers and challenges

    Directory of Open Access Journals (Sweden)

    Larry L. Hench

    2015-11-01

    Full Text Available Bioactive glasses were discovered in 1969 and provided for the first time an alternative to nearly inert implant materials. Bioglass formed a rapid, strong and stable bond with host tissues. This article examines the frontiers of research crossed to achieve clinical use of bioactive glasses and glass-ceramics. In the 1980’s it was discovered that bioactive glasses could be used in particulate form to stimulate osteogenesis, which thereby led to the concept of regeneration of tissues. Later, it was discovered that the dissolution ions from the glasses behaved like growth factors, providing signals to the cells. This article summarizes the frontiers of knowledge crossed during four eras of development of bioactive glasses that have led from concept of bioactivity to widespread clinical and commercial use, with emphasis on the first composition, 45S5 Bioglass®. The four eras are: a discovery; b clinical application; c tissue regeneration; and d innovation. Questions still to be answered for the fourth era are included to stimulate innovation in the field and exploration of new frontiers that can be the basis for a general theory of bioactive stimulation of regeneration of tissues and application to numerous clinical needs.

  16. Bioactive proteins from pipefishes

    Directory of Open Access Journals (Sweden)

    E. Rethna Priya

    2013-01-01

    Full Text Available Objective: To screen antimicrobial potence of some pipefish species collected from Tuticorin coastal environment. Methods: Antimicrobial activity of pipefishes in methanol extract was investigated against 10 bacterial and 10 fungal human pathogenic strains. Results: Among the tested strains, in Centriscus scutatus, pipefish showed maximum zone of inhibition against Vibrio cholerae (8 mm and minimum in the sample of Hippichthys cyanospilos against Klebseilla pneumoniae (2 mm. In positive control, maximum zone of inhibition was recorded in Vibrio cholerae (9 mm and minimum in Klebseilla pneumoniae, and Salmonella paratyphi (5 mm. Chemical investigation indicated the presence of peptides as evidenced by ninhydrin positive spots on thin layer chromatography and presence of peptide. In SDS PAGE, in Centriscus scutatus, four bands were detected in the gel that represented the presence of proteins in the range nearly 25.8-75 kDa. In Hippichthys cyanospilos, five bands were detected in the gel that represented the presence of proteins in the range nearly 20.5-78 kDa. The result of FT-IR spectrum revealed that the pipe fishes extracts compriseed to have peptide derivatives as their predominant chemical groups. Conclusions: It can be conclude that this present investigation suggests the tested pipe fishes will be a potential source of natural bioactive compounds.

  17. Bioactive proteins from pipefishes

    Directory of Open Access Journals (Sweden)

    E. Rethna Priya

    2013-08-01

    Full Text Available Objective: To screen antimicrobial potence of some pipefish species collected from Tuticorin coastal environment. Methods: Antimicrobial activity of pipefishes in methanol extract was investigated against 10 bacterial and 10 fungal human pathogenic strains. Results: Among the tested strains, in Centriscus scutatus, pipefish showed maximum zone of inhibition against Vibrio cholerae (8 mm and minimum in the sample of Hippichthys cyanospilos against Klebseilla pneumoniae (2 mm. In positive control, maximum zone of inhibition was recorded in Vibrio cholerae (9 mm and minimum in Klebseilla pneumoniae, and Salmonella paratyphi (5 mm. Chemical investigation indicated the presence of peptides as evidenced by ninhydrin positive spots on thin layer chromatography and presence of peptide. In SDS PAGE, in Centriscus scutatus, four bands were detected in the gel that represented the presence of proteins in the range nearly 25.8-75 kDa. In Hippichthys cyanospilos, five bands were detected in the gel that represented the presence of proteins in the range nearly 20.5-78 kDa. The result of FT-IR spectrum revealed that the pipe fishes extracts compriseed to have peptide derivatives as their predominant chemical groups. Conclusions: It can be conclude that this present investigation suggests the tested pipe fishes will be a potential source of natural bioactive compounds.

  18. The signaling lipid sphingosine 1-phosphate regulates mechanical pain

    Science.gov (United States)

    Hill, Rose Z; Hoffman, Benjamin U; Morita, Takeshi; Campos, Stephanie M; Lumpkin, Ellen A; Brem, Rachel B

    2018-01-01

    Somatosensory neurons mediate responses to diverse mechanical stimuli, from innocuous touch to noxious pain. While recent studies have identified distinct populations of A mechanonociceptors (AMs) that are required for mechanical pain, the molecular underpinnings of mechanonociception remain unknown. Here, we show that the bioactive lipid sphingosine 1-phosphate (S1P) and S1P Receptor 3 (S1PR3) are critical regulators of acute mechanonociception. Genetic or pharmacological ablation of S1PR3, or blockade of S1P production, significantly impaired the behavioral response to noxious mechanical stimuli, with no effect on responses to innocuous touch or thermal stimuli. These effects are mediated by fast-conducting A mechanonociceptors, which displayed a significant decrease in mechanosensitivity in S1PR3 mutant mice. We show that S1PR3 signaling tunes mechanonociceptor excitability via modulation of KCNQ2/3 channels. Our findings define a new role for S1PR3 in regulating neuronal excitability and establish the importance of S1P/S1PR3 signaling in the setting of mechanical pain thresholds. PMID:29561262

  19. Inhibition of haemoglobin-mediated lipid oxidation in washed cod muscle and cod protein isolates by Fucus vesiculosus extract and fraction

    DEFF Research Database (Denmark)

    Wang, Tao; Jonsdottir, Rosa; Kristinsson, Hordur

    2010-01-01

    washed cod muscle and protein isolates, phlorotannin-enriched ethyl acetate (EtOAc) fraction showed higher inhibitory effect than crude 80% ethanol (EtOH) extract. The addition of oligomeric phlorotannin-rich subfraction (LH-2) separated by Sephadex LH-20 chromatography, completely inhibited...... similar level of TPC and chemical antioxidant activities as oligomeric subfraction LH-2, it was far less efficient in model systems. These results suggest that other factors rather than the intrinsic reactivity toward radicals could be responsible for the inhibitory effect of phlorotannins on lipid...

  20. Raft-mediated trafficking of apical resident proteins occurs in both direct and transcytotic pathways in polarized hepatic cells : Role of distinct lipid microdomains

    NARCIS (Netherlands)

    Slimane, TA; Trugnan, G; van Ijzendoorn, SCD; Hoekstra, D

    In polarized hepatic cells, pathways and molecular principles mediating the flow of resident apical bile canalicular proteins have not yet been resolved. Herein, we have investigated apical trafficking of a glycosylphosphatidylinositol-linked and two single transmembrane domain proteins on the one

  1. Lipid Nanotechnology

    Directory of Open Access Journals (Sweden)

    Gijsje Koenderink

    2013-02-01

    Full Text Available Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices and machines derived from engineering, physics, materials science, chemistry and biology. These devices have found applications in biomedical sciences, such as targeted drug delivery, bio-imaging, sensing and diagnosis of pathologies at early stages. In these applications, nano-devices typically interface with the plasma membrane of cells. On the other hand, naturally occurring nanostructures in biology have been a source of inspiration for new nanotechnological designs and hybrid nanostructures made of biological and non-biological, organic and inorganic building blocks. Lipids, with their amphiphilicity, diversity of head and tail chemistry, and antifouling properties that block nonspecific binding to lipid-coated surfaces, provide a powerful toolbox for nanotechnology. This review discusses the progress in the emerging field of lipid nanotechnology.

  2. Bioactive composite for keratoprosthesis skirt.

    Science.gov (United States)

    Laattala, Kaisa; Huhtinen, Reeta; Puska, Mervi; Arstila, Hanna; Hupa, Leena; Kellomäki, Minna; Vallittu, Pekka K

    2011-11-01

    In this study, the fabrication and properties of a synthetic keratoprosthesis skirt for use in osteo-odonto-keratoprosthesis (OOKP) surgery are discussed. In the search for a new material concept, bioactive glass and polymethyl methacrylate (PMMA)-based composites were prepared. Three different bioactive glasses (i.e. 45S5, S53P4 and 1-98) and one slowly resorbing glass, FL107, with two different forms (i.e. particles and porous glass structures) were employed in the fabrication of specimens. In in vitro studies, the dissolution behaviour in simulated aqueous humour, compressive properties, and pore formation of the composites were investigated. According to the results, FL107 dissolved very slowly (2.4% of the initial glass content in three weeks); thus, the pore formation of the FL107 composite was also observed to be restricted. The dissolution rates of the bioactive glass-PMMA composites were greater (12%-17%). These faster dissolving bioactive glass particles caused some porosity on the outermost surfaces of the composite. The slight surface porosity was also confirmed by a decrease in compressive properties. During six weeks' in vitro dissolution, the compressive strength of the test specimens containing particles decreased by 22% compared to values in dry conditions (90-107 MPa). These results indicate that the bioactive composites could be stable synthetic candidates for a keratoprosthesis skirt in the treatment of severely damaged or diseased cornea. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Aerobic exercise regulates blood lipid and insulin resistance via the toll‑like receptor 4‑mediated extracellular signal‑regulated kinases/AMP‑activated protein kinases signaling pathway.

    Science.gov (United States)

    Wang, Mei; Li, Sen; Wang, Fubaihui; Zou, Jinhui; Zhang, Yanfeng

    2018-06-01

    ІІ diabetes mellitus. The activity of ERK and AMPK, and the function of islet β‑cells were observed to be improved in experimental mice treated with aerobic exercise. Furthermore, blood lipid metabolism and insulin resistance were improved by treatment with aerobic exercise. Body weight and glucose concentration of serology was markedly improved in mouse models of type‑ІІ diabetes mellitus. Furthermore, TLR‑4 inhibition markedly promoted ERK and AMPK expression levels and activity. Thus, these results indicate that aerobic exercise may improve blood lipid metabolism, insulin resistance and glucose plasma concentration in mouse models of type‑ІІ diabetes mellitus. Thus indicating aerobic exercise is beneficial for improvement of blood lipid and insulin resistance via the TLR‑4‑mediated ERK/AMPK signaling pathway in the progression of type‑ІІ diabetes mellitus.

  4. Synthesis and in vitro bioactivity of mesoporous bioactive glass scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Shih, C.J., E-mail: cjshih@kmu.edu.tw [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chen, H.T. [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Huang, L.F. [School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Lu, P.S.; Chang, H.F. [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, I.L., E-mail: 84004@cch.org.tw [Department of Orthopaedic Surgery, Chang-Hua Christian Hospital, Changhua 500, Taiwan (China)

    2010-06-15

    The main objective of the present study was to determine the effect of thermal treatment procedures (calcination temperature, heating rate and duration time) on the synthesis of SiO{sub 2}-CaO-P{sub 2}O{sub 5} mesoporous bioactive glass scaffolds. This is accomplished by thermogravimetric analyses, Fourier transform infrared (FTIR) absorption spectra, X-ray diffraction (XRD) and by analysis of nitrogen adsorption/desorption isotherms. In vitro bioactivity can also be assessed by the cytotoxic effect of the glasses on the NIH-3T3 cell line, and by characterization of MC-3T3-E1 cell attachment.

  5. Synthesis and in vitro bioactivity of mesoporous bioactive glass scaffolds

    International Nuclear Information System (INIS)

    Shih, C.J.; Chen, H.T.; Huang, L.F.; Lu, P.S.; Chang, H.F.; Chang, I.L.

    2010-01-01

    The main objective of the present study was to determine the effect of thermal treatment procedures (calcination temperature, heating rate and duration time) on the synthesis of SiO 2 -CaO-P 2 O 5 mesoporous bioactive glass scaffolds. This is accomplished by thermogravimetric analyses, Fourier transform infrared (FTIR) absorption spectra, X-ray diffraction (XRD) and by analysis of nitrogen adsorption/desorption isotherms. In vitro bioactivity can also be assessed by the cytotoxic effect of the glasses on the NIH-3T3 cell line, and by characterization of MC-3T3-E1 cell attachment.

  6. Tumor necrosis factor alpha is associated with insulin-mediated suppression of free fatty acids and net lipid oxidation in HIV-infected patients with lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, SB; Andersen, O; Pedersen, Steen Bønløkke

    2006-01-01

    Tumor necrosis factor alpha (TNF-alpha) stimulates lipolysis in man. We examined whether plasma TNF-alpha is associated with the degree by which insulin suppresses markers of lipolysis, for example, plasma free fatty acid (FFA) and net lipid oxidation (LIPOX) rate in HIV-infected patients...... with lipodystrophy (LIPO) and those without (controls). LIPOX was estimated by indirect calorimetry during fasting and steady state of a hyperinsulinemic euglycemic clamp in 36 (18 LIPO and 18 controls) normoglycemic HIV-infected men on highly active antiretroviral therapy. In LIPO, TNF-alpha correlated with clamp...... were significant in controls. In all patients, TNF-alpha correlated with clamp FFA (r = 0.61, P

  7. Curcuma longa polyphenols improve insulin-mediated lipid accumulation and attenuate proinflammatory response of 3T3-L1 adipose cells during oxidative stress through regulation of key adipokines and antioxidant enzymes.

    Science.gov (United States)

    Septembre-Malaterre, Axelle; Le Sage, Fanny; Hatia, Sarah; Catan, Aurélie; Janci, Laurent; Gonthier, Marie-Paule

    2016-07-08

    Plant polyphenols may exert beneficial action against obesity-related oxidative stress and inflammation which promote insulin resistance. This study evaluated the effect of polyphenols extracted from French Curcuma longa on 3T3-L1 adipose cells exposed to H2 O2 -mediated oxidative stress. We found that Curcuma longa extract exhibited high amounts of curcuminoids identified as curcumin, demethoxycurcumin, and bisdemethoxycurcumin, which exerted free radical-scavenging activities. Curcuma longa polyphenols improved insulin-mediated lipid accumulation and upregulated peroxisome proliferator-activated receptor-gamma gene expression and adiponectin secretion which decreased in H2 O2 -treated cells. Curcuminoids attenuated H2 O2 -enhanced production of pro-inflammatory molecules such as interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and nuclear factor κappa B. Moreover, they reduced intracellular levels of reactive oxygen species elevated by H2 O2 and modulated the expression of genes encoding superoxide dismutase and catalase antioxidant enzymes. Collectively, these findings highlight that Curcuma longa polyphenols protect adipose cells against oxidative stress and may improve obesity-related metabolic disorders. © 2016 BioFactors, 42(4):418-430, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  8. Lipid Panel

    Science.gov (United States)

    ... A routine cardiac risk assessment typically includes a fasting lipid panel. Beyond that, research continues into the usefulness of other non-traditional markers of cardiac risk, such as Lp-PLA 2 . A health practitioner may choose to evaluate one or more ...

  9. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    . In particular, 3-15% of very low birth weight preterm infants suffer from the most servere form of intestinal inflammation, known as necrotizing enterocolitis (NEC). This disease is incurable with a high mortality rate of 15-30%. Mother’s breast milk consists of different bioactive constituents...... of infant formula. Thereafter, bioactive milk components which were preserved in gently-processed infant formula were selected for further investigation of their immunomodulatory activity in cell and preterm pig models. We hope this project will contribute to the research on the development of new...

  10. LipidPedia: a comprehensive lipid knowledgebase.

    Science.gov (United States)

    Kuo, Tien-Chueh; Tseng, Yufeng Jane

    2018-04-10

    Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging. Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3,923 lipids and more than 400,000 annotations of associated diseases, pathways, functions, and locations that are essential for interpreting lipid functions and mechanisms from over 1,400,000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms. LipidPedia is available at http://lipidpedia.cmdm.tw. yjtseng@csie.ntu.edu.tw. Supplementary data are available at Bioinformatics online.

  11. pH-Responsive therapeutic solid lipid nanoparticles for reducing P-glycoprotein-mediated drug efflux of multidrug resistant cancer cells

    Directory of Open Access Journals (Sweden)

    Chen HH

    2015-08-01

    Full Text Available Hsin-Hung Chen,1 Wen-Chia Huang,2 Wen-Hsuan Chiang,2 Te-I Liu,2 Ming-Yin Shen,2,3 Yuan-Hung Hsu,4 Sung-Chyr Lin,1 Hsin-Cheng Chiu2 1Department of Chemical Engineering, National Chung Hsing University, Taichung, 2Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 3Department of Surgery, National Taiwan University Hospital-Hsinchu Branch, 4Pharmaceutical Optimization Technology Division, Biomedical Technology and Device Research Laboratory, Industrial Technology Research Institute, Hsinchu, Taiwan Abstract: In this study, a novel pH-responsive cholesterol-PEG adduct-coated solid lipid nanoparticles (C-PEG-SLNs carrying doxorubicin (DOX capable of overcoming multidrug resistance (MDR breast cancer cells is presented. The DOX-loaded SLNs have a mean hydrodynamic diameter of ~100 nm and a low polydispersity index (under 0.20 with a high drug-loading efficiency ranging from 80.8% to 90.6%. The in vitro drug release profiles show that the DOX-loaded SLNs exhibit a pH-controlled drug release behavior with the maximum and minimum unloading percentages of 63.4% at pH 4.7 and 25.2% at pH 7.4, respectively. The DOX-loaded C-PEG-SLNs displayed a superior ability in inhibiting the proliferation of MCF-7/MDR cells. At a DOX concentration of 80 µM, the cell viabilities treated with C-PEG-SLNs were approximately one-third of the group treated with free DOX. The inhibition activity of C-PEG-SLNs could be attributed to the transport of C-PEG to cell membrane, leading to the change of the composition of the cell membrane and thus the inhibition of permeability glycoprotein activity. This hypothesis is supported by the confocal images showing the accumulation of DOX in the nuclei of cancer cells and the localization of C-PEG on the cell membranes. The results of in vivo study further demonstrated that the DOX delivered by the SLNs accumulates predominantly in tumor via enhanced permeability and retention effect, the

  12. Membrane-Associated Effects of Glucocorticoid on BACE1 Upregulation and Aβ Generation: Involvement of Lipid Raft-Mediated CREB Activation.

    Science.gov (United States)

    Choi, Gee Euhn; Lee, Sei-Jung; Lee, Hyun Jik; Ko, So Hee; Chae, Chang Woo; Han, Ho Jae

    2017-08-30

    Glucocorticoid has been widely accepted to induce Alzheimer's disease, but the nongenomic effect of glucocorticoid on amyloid β (Aβ) generation has yet to be studied. Here, we investigated the effect of the nongenomic pathway induced by glucocorticoid on amyloid precursor protein processing enzymes as well as Aβ production using male ICR mice and human neuroblastoma SK-N-MC cells. Mice groups exposed to restraint stress or intracerebroventricular injection of Aβ showed impaired cognition, decreased intracellular glucocorticoid receptor (GR) level, but elevated level of membrane GR (mGR). In this respect, we identified the mGR-dependent pathway evoked by glucocorticoid using impermeable cortisol conjugated to BSA (cortisol-BSA) on SK-N-MC cells. Cortisol-BSA augmented the expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), the level of C-terminal fragment β of amyloid precursor protein (C99) and Aβ production, which were maintained even after blocking intracellular GR. We also found that cortisol-BSA enhanced the interaction between mGR and Gαs, which colocalized in the lipid raft. The subsequently activated CREB by cortisol-BSA bound to the CRE site of the BACE1 promoter increasing its expression, which was downregulated by inhibiting CBP. Consistently, blocking CBP attenuated cognitive impairment and Aβ production induced by corticosterone treatment or intracerebroventricular injection of Aβ more efficiently than inhibiting intracellular GR in mice. In conclusion, glucocorticoid couples mGR with Gαs and triggers cAMP-PKA-CREB axis dependent on the lipid raft to stimulate BACE1 upregulation and Aβ generation. SIGNIFICANCE STATEMENT Patients with Alzheimer's disease (AD) have been growing sharply and stress is considered as the major environment factor of AD. Glucocorticoid is the primarily responsive factor to stress and is widely known to induce AD. However, most AD patients usually have impaired genomic pathway of glucocorticoid

  13. Bioactive glasses potential biomaterials for future therapy

    CERN Document Server

    Kaur, Gurbinder

    2017-01-01

    This book describes the history, origin and basic characteristics of bioactive materials. It includes a chapter dedicated to hydroxyapatite mineral, its formation and its bioactive properties. The authors address how cytotoxicity is a determining step for bioactivity. Applications of bioactive materials in the contexts of tissue regeneration, bone regeneration and cancer therapy are also covered. Silicate, metallic and mesoporous glasses are described, as well as the challenges and future prospects of research in this field.

  14. Structure of lipid kinase p110β/p85β elucidates an unusual SH2-domain-mediated inhibitory mechanism.

    Science.gov (United States)

    Zhang, Xuxiao; Vadas, Oscar; Perisic, Olga; Anderson, Karen E; Clark, Jonathan; Hawkins, Phillip T; Stephens, Len R; Williams, Roger L

    2011-03-04

    Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. The structure of a p110β/p85β complex identifies an inhibitory function for the C-terminal SH2 domain (cSH2) of the p85 regulatory subunit. Mutagenesis of a cSH2 contact residue activates downstream signaling in cells. This inhibitory contact ties up the C-terminal region of the p110β catalytic subunit, which is essential for lipid kinase activity. In vitro, p110β basal activity is tightly restrained by contacts with three p85 domains: the cSH2, nSH2, and iSH2. RTK phosphopeptides relieve inhibition by nSH2 and cSH2 using completely different mechanisms. The binding site for the RTK's pYXXM motif is exposed on the cSH2, requiring an extended RTK motif to reach and disrupt the inhibitory contact with p110β. This contrasts with the nSH2 where the pY-binding site itself forms the inhibitory contact. This establishes an unusual mechanism by which p85 SH2 domains contribute to RTK signaling specificities. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Bio-actives and Drug

    Indian Academy of Sciences (India)

    Bio-actives. have an effect on or elicit a response from living tissue. Refer to a substance that can be acted upon by a living organism or by an extract from a living organism. are constituents in foods or dietary supplements, other than those needed to meet basic nutritional needs, that are responsible for changes in health ...

  16. Fisetin Suppresses Lipid Accumulation in Mouse Adipocytic 3T3-L1 Cells by Repressing GLUT4-Mediated Glucose Uptake through Inhibition of mTOR-C/EBPα Signaling.

    Science.gov (United States)

    Watanabe, Marina; Hisatake, Mitsuhiro; Fujimori, Ko

    2015-05-27

    3,7,3',4'-Tetrahydroxyflavone (fisetin) is a flavonoid found in vegetables and fruits having broad biological activities. Here the effects of fisetin on adipogenesis and its regulatory mechanism in mouse adipocytic 3T3-L1 cells are studied. Fisetin inhibited the accumulation of intracellular lipids and lowered the expression of adipogenic genes such as peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein (C/EBP) α and fatty acid-binding protein 4 (aP2) during adipogenesis. Moreover, the mRNA levels of genes such as acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase involved in the fatty acid biosynthesis (lipogenesis) were reduced by the treatment with fisetin. The expression level of the glucose transporter 4 (GLUT4) gene was also decreased by fisetin, resulting in down-regulation of glucose uptake. Furthermore, fisetin inhibited the phosphorylation of the mammalian target of rapamycin (mTOR) and that of p70 ribosomal S6 kinase, a target of the mTOR complex, the inhibition of which was followed by a decreased mRNA level of the C/EBPα gene. The results obtained from a chromatin immunoprecipitation assay demonstrated that the ability of C/EBPα to bind to the GLUT4 gene promoter was reduced by the treatment with fisetin, which agreed well with those obtained when 3T3-L1 cells were allowed to differentiate into adipocytes in medium in the presence of rapamycin, an inhibitor for mTOR. These results indicate that fisetin suppressed the accumulation of intracellular lipids by inhibiting GLUT4-mediated glucose uptake through inhibition of the mTOR-C/EBPα signaling in 3T3-L1 cells.

  17. The dynamic of lipid oxidation in human myotubes

    DEFF Research Database (Denmark)

    Gaster, Michael

    2009-01-01

    Both endogenous and exogenous lipid levels may be regulators of total lipid oxidation in skeletal muscles. We studied the dynamics of lipid oxidation in human myotubes established from healthy, lean subjects exposed to acutely and chronically increased palmitate concentrations. The intramyocellular...... triacylglycerol content increased with chronic palmitate exposure. Both, ectopically increased intracellular and extracellular lipid levels were simultaneously oxidized and could partly suppress each other's oxidation. Overall, the highest acute palmitate treatments stimulated fatty acid oxidation whilst...... the highest chronic treatments decreased total lipid oxidation. Intracellular lipids showed a more complete oxidation than exogenous lipids. Endogenous lipids reduced insulin-mediated glucose oxidation. Thus, both endogenous and exogenous lipid concentrations regulated each other's oxidation and total lipid...

  18. The role of the kidney in lipid metabolism

    DEFF Research Database (Denmark)

    Moestrup, Søren K; Nielsen, Lars Bo

    2005-01-01

    PURPOSE OF REVIEW: Cellular uptake of plasma lipids is to a large extent mediated by specific membrane-associated proteins that recognize lipid-protein complexes. In the kidney, the apical surface of proximal tubules has a high capacity for receptor-mediated uptake of filtered lipid-binding plasma...... proteins. We describe the renal receptor system and its role in lipid metabolism in health and disease, and discuss the general effect of the diseased kidney on lipid metabolism. RECENT FINDINGS: Megalin and cubilin are receptors in the proximal tubules. An accumulating number of lipid......-binding and regulating proteins (e.g. albumin, apolipoprotein A-I and leptin) have been identified as ligands, suggesting that their receptors may directly take up lipids in the proximal tubules and indirectly affect plasma and tissue lipid metabolism. Recently, the amnionless protein was shown to be essential...

  19. Degradation of lipid regulators by the UV/chlorine process: Radical mechanisms, chlorine oxide radical (ClO•)-mediated transformation pathways and toxicity changes.

    Science.gov (United States)

    Kong, Xiujuan; Wu, Zihao; Ren, Ziran; Guo, Kaiheng; Hou, Shaodong; Hua, Zhechao; Li, Xuchun; Fang, Jingyun

    2018-06-15

    Degradation of three lipid regulators, i.e., gemfibrozil, bezafibrate and clofibric acid, by a UV/chlorine treatment was systematically investigated. The chlorine oxide radical (ClO • ) played an important role in the degradation of gemfibrozil and bezafibrate with second-order rate constants of 4.2 (±0.3) × 10 8  M -1  s -1 and 3.6 (±0.1) × 10 7  M -1  s -1 , respectively, whereas UV photolysis and the hydroxyl radical (HO • ) mainly contributed to the degradation of clofibric acid. The first-order rate constants (k') for the degradation of gemfibrozil and bezafibrate increased linearly with increasing chlorine dosage, primarily due to the linear increase in the ClO • concentration. The k' values for gemfibrozil, bezafibrate, and clofibric acid degradation decreased with increasing pH from 5.0 to 8.4; however, the contribution of the reactive chlorine species (RCS) increased. Degradation of gemfibrozil and bezafibrate was enhanced in the presence of Br - , whereas it was inhibited in the presence of natural organic matter (NOM). The presence of ammonia at a chlorine: ammonia molar ratio of 1:1 resulted in decreases in the k' values for gemfibrozil and bezafibrate of 69.7% and 7%, respectively, but led to an increase in that for clofibric acid of 61.8%. Degradation of gemfibrozil by ClO • was initiated by hydroxylation and chlorine substitution on the benzene ring. Then, subsequent hydroxylation, bond cleavage and chlorination reactions led to the formation of more stable products. Three chlorinated intermediates were identified during ClO • oxidation process. Formation of the chlorinated disinfection by-products chloral hydrate and 1,1,1-trichloropropanone was enhanced relative to that of other by-products. The acute toxicity of gemfibrozil to Vibrio fischeri increased significantly when subjected to direct UV photolysis, whereas it decreased when oxidized by ClO • . This study is the first to report the transformation pathway of a

  20. Lipid phase control of DNA delivery

    Energy Technology Data Exchange (ETDEWEB)

    Koynova, Rumiana; Wang, Li; Tarahovsky, Yury; MacDonald, Robert C. (NWU)

    2010-01-18

    Cationic lipids form nanoscale complexes (lipoplexes) with polyanionic DNA and can be utilized to deliver DNA to cells for transfection. Here we report the correlation between delivery efficiency of these DNA carriers and the mesomorphic phases they form when interacting with anionic membrane lipids. Specifically, formulations that are particularly effective DNA carriers form phases of highest negative interfacial curvature when mixed with anionic lipids, whereas less effective formulations form phases of lower curvature. Structural evolution of the carrier lipid/DNA complexes upon interaction with cellular lipids is hence suggested as a controlling factor in lipid-mediated DNA delivery. A strategy for optimizing lipofection is deduced. The behavior of a highly effective lipoplex formulation, DOTAP/DOPE, is found to conform to this 'efficiency formula'.

  1. The pro-resolving lipid mediator Maresin 1 protects against cerebral ischemia/reperfusion injury by attenuating the pro-inflammatory response

    International Nuclear Information System (INIS)

    Xian, Wenjing; Wu, Yan; Xiong, Wei; Li, Longyan; Li, Tong; Pan, Shangwen; Song, Limin; Hu, Lisha; Pei, Lei; Yao, Shanglong

    2016-01-01

    Inflammation plays a crucial role in acute ischemic stroke pathogenesis. Macrophage-derived Maresin 1 (MaR1) is a newly uncovered mediator with potent anti-inflammatory abilities. Here, we investigated the effect of MaR1 on acute inflammation and neuroprotection in a mouse brain ischemia reperfusion (I/R) model. Male C57 mice were subjected to 1-h middle cerebral artery occlusion (MCAO) and reperfusion. By the methods of 2,3,5-triphenyltetrazolium chloride, haematoxylin and eosin or Fluoro-Jade B staining, neurological deficits scoring, ELISA detection, immunofluorescence assay and western blot analysis, we found that intracerebroventricular injection of MaR1 significantly reduced the infarct volume and neurological defects, essentially protected the brain tissue and neurons from injury, alleviated pro-inflammatory reactions and NF-κB p65 activation and nuclear translocation. Taken together, our results suggest that MaR1 significantly protects against I/R injury probably by inhibiting pro-inflammatory reactions. - Highlights: • MaR1 significantly protects against ischemia reperfusion injury. • MaR1 inhibits pro-inflammatory cytokines and chemokines and reducing glial activation and neutrophil infiltration. • These effects at least partially occurred via suppression of the NF-κB p65 signalling pathway.

  2. The pro-resolving lipid mediator Maresin 1 protects against cerebral ischemia/reperfusion injury by attenuating the pro-inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Xian, Wenjing [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wu, Yan [Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xiong, Wei [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Li, Longyan [Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Li, Tong [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Pan, Shangwen [Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Song, Limin [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Hu, Lisha [Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Pei, Lei [Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Yao, Shanglong, E-mail: ysltian@163.com [Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); and others

    2016-03-25

    Inflammation plays a crucial role in acute ischemic stroke pathogenesis. Macrophage-derived Maresin 1 (MaR1) is a newly uncovered mediator with potent anti-inflammatory abilities. Here, we investigated the effect of MaR1 on acute inflammation and neuroprotection in a mouse brain ischemia reperfusion (I/R) model. Male C57 mice were subjected to 1-h middle cerebral artery occlusion (MCAO) and reperfusion. By the methods of 2,3,5-triphenyltetrazolium chloride, haematoxylin and eosin or Fluoro-Jade B staining, neurological deficits scoring, ELISA detection, immunofluorescence assay and western blot analysis, we found that intracerebroventricular injection of MaR1 significantly reduced the infarct volume and neurological defects, essentially protected the brain tissue and neurons from injury, alleviated pro-inflammatory reactions and NF-κB p65 activation and nuclear translocation. Taken together, our results suggest that MaR1 significantly protects against I/R injury probably by inhibiting pro-inflammatory reactions. - Highlights: • MaR1 significantly protects against ischemia reperfusion injury. • MaR1 inhibits pro-inflammatory cytokines and chemokines and reducing glial activation and neutrophil infiltration. • These effects at least partially occurred via suppression of the NF-κB p65 signalling pathway.

  3. Lipid shell-enveloped polymeric nanoparticles with high integrity of lipid shells improve mucus penetration and interaction with cystic fibrosis-related bacterial biofilms

    DEFF Research Database (Denmark)

    Wan, Feng; Nylander, Tommy; Klodzinska, Sylvia Natalie

    2018-01-01

    , we describe facile methods to prepare Lipid@NPs with high integrity of lipid shells and demonstrate the potential of Lipid@NPs in effective mucus penetration and interaction with cystic fibrosis-related bacterial biofilms. Lipid shell-enveloped polystyrene NPs with high integrity of lipid shells (c...... mediated layer-by layer approach. Our results suggest that the integrity of the lipid envelopes is crucial for enabling the diffusion of Lipid@PSNPs into the mucus layer and promoting the interaction of Lipid@PSNPs with a bacterial biofilm....

  4. Stimulatory effects of combined endocrine disruptors on MA-10 Leydig cell steroid production and lipid homeostasis

    International Nuclear Information System (INIS)

    Jones, Steven; Boisvert, Annie; Naghi, Andrada; Hullin-Matsuda, Françoise; Greimel, Peter; Kobayashi, Toshihide; Papadopoulos, Vassilios; Culty, Martine

    2016-01-01

    Previous work in our laboratory demonstrated that in-utero exposure to a mixture of the phytoestrogen Genistein (GEN), and plasticizer DEHP, induces short- and long-term alterations in testicular gene and protein expression different from individual exposures. These studies identified fetal and adult Leydig cells as sensitive targets for low dose endocrine disruptor (ED) mixtures. To further investigate the direct effects and mechanisms of toxicity of GEN and DEHP, MA-10 mouse tumor Leydig cells were exposed in-vitro to varying concentrations of GEN and MEHP, the principal bioactive metabolite of DEHP. Combined 10 μM GEN + 10 μM MEHP had a stimulatory effect on basal progesterone production. Consistent with increased androgenicity, the mRNA of steroidogenic and cholesterol mediators Star, Cyp11a, Srb1 and Hsl, as well as upstream orphan nuclear receptors Nr2f2 and Sf1 were all significantly increased uniquely in the mixture treatment group. Insl3, a sensitive marker of Leydig endocrine disruption and cell function, was significantly decreased by combined GEN + MEHP. Lipid analysis by high-performance thin layer chromatography demonstrated the ability of combined 10 μM combined GEN + MEHP, but not individual exposures, to increase levels of several neutral lipids and phospholipid classes, indicating a generalized deregulation of lipid homeostasis. Further investigation by qPCR analysis revealed a concomitant increase in cholesterol (Hmgcoa) and phospholipid (Srebp1c, Fasn) mediator mRNAs, suggesting the possible involvement of upstream LXRα agonism. These results suggest a deregulation of MA-10 Leydig function in response to a combination of GEN + MEHP. We propose a working model for GEN + MEHP doses relevant to human exposure involving LXR agonism and activation of other transcription factors. Taken more broadly, this research highlights the importance of assessing the impact of ED mixtures in multiple toxicological models across a range of environmentally

  5. Marine Peptides: Bioactivities and Applications

    Directory of Open Access Journals (Sweden)

    Randy Chi Fai Cheung

    2015-06-01

    Full Text Available Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant, immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products.

  6. Maize Bioactive Peptides against Cancer

    Science.gov (United States)

    Díaz-Gómez, Jorge L.; Castorena-Torres, Fabiola; Preciado-Ortiz, Ricardo E.; García-Lara, Silverio

    2017-06-01

    Cancer is one of the main chronic degenerative diseases worldwide. In recent years, consumption of whole-grain cereals and their derived food products has been associated with reduction risks of various types of cancer. Cereals main biomolecules includes proteins, peptides, and amino acids present in different quantities within the grain. The nutraceutical properties associated with peptides exerts biological functions that promote health and prevent this disease. In this review, we report the current status and advances on maize peptides regarding bioactive properties that have been reported such as antioxidant, antihypertensive, hepatoprotective, and anti-tumour activities. We also highlighted its biological potential through which maize bioactive peptides exert anti-cancer activity. Finally, we analyse and emphasize the possible areas of application for maize peptides.

  7. The unusual lipid binding proteins of parasitic helminths and their potential roles in parasitism and as therapeutic targets.

    Science.gov (United States)

    Franchini, Gisela R; Pórfido, Jorge L; Ibáñez Shimabukuro, Marina; Rey Burusco, María F; Bélgamo, Julián A; Smith, Brian O; Kennedy, Malcolm W; Córsico, Betina

    2015-02-01

    In this review paper we aim at presenting the current knowledge on structural aspects of soluble lipid binding proteins (LBPs) found in parasitic helminths and to discuss their potential role as novel drug targets. Helminth parasites produce and secrete a great variety of LBPs that may participate in the acquisition of nutrients from their host, such as fatty acids and cholesterol. It is also postulated that LBPs might interfere in the regulation of the host׳s immune response by sequestering lipidic intermediates or delivering bioactive lipids. A detailed comprehension of the structure of these proteins, as well as their interactions with ligands and membranes, is important to understand host-parasite relationships that they may mediate. This information could also contribute to determining the role that these proteins may play in the biology of parasitic helminths and how they modulate the immune systems of their hosts, and also towards the development of new therapeutics and prevention of the diseases caused by these highly pathogenic parasites. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Applications of lipid based formulation technologies in the delivery of biotechnology-based therapeutics.

    Science.gov (United States)

    du Plessis, Lissinda H; Marais, Etienne B; Mohammed, Faruq; Kotzé, Awie F

    2014-01-01

    In the last decades several new biotechnologically-based therapeutics have been developed due to progress in genetic engineering. A growing challenge facing pharmaceutical scientists is formulating these compounds into oral dosage forms with adequate bioavailability. An increasingly popular approach to formulate biotechnology-based therapeutics is the use of lipid based formulation technologies. This review highlights the importance of lipid based drug delivery systems in the formulation of oral biotechnology based therapeutics including peptides, proteins, DNA, siRNA and vaccines. The different production procedures used to achieve high encapsulation efficiencies of the bioactives are discussed, as well as the factors influencing the choice of excipient. Lipid based colloidal drug delivery systems including liposomes and solid lipid nanoparticles are reviewed with a focus on recent advances and updates. We further describe microemulsions and self-emulsifying drug delivery systems and recent findings on bioactive delivery. We conclude the review with a few examples on novel lipid based formulation technologies.

  9. Hierarchical Structures and Shaped Particles of Bioactive Glass and Its In Vitro Bioactivity

    Directory of Open Access Journals (Sweden)

    U. Boonyang

    2013-01-01

    Full Text Available In this study, bioactive glass particles with controllable structure and porosity were prepared using dual-templating methods. Block copolymers used as one template component produced mesopores in the calcined samples. Polymer colloidal crystals as the other template component yielded either three-dimensionally ordered macroporous (3DOM products or shaped bioactive glass nanoparticles. The in vitro bioactivity of these bioactive glasses was studied by soaking the samples in simulated body fluid (SBF at body temperature (37°C for varying lengths of time and monitoring the formation of bone-like apatite on the surface of the bioactive glass. A considerable bioactivity was found that all of bioactive glass samples have the ability to induce the formation of an apatite layer on its surface when in contact with SBF. The development of bone-like apatite is faster for 3DOM bioactive glasses than for nanoparticles.

  10. Nutrients, phytochemicals and bioactivity of wild Roman chamomile: a comparison between the herb and its preparations

    OpenAIRE

    Guimarães, Rafaela; Barros, Lillian; Dueñas, Montserrat; Calhelha, Ricardo C.; Carvalho, Ana Maria; Santos-Buelga, Celestino; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R.

    2013-01-01

    Roman chamomile, Chamaemelum nobile L. (Asteraceae), has been used for medicinal applications, mainly through oral dosage forms (decoctions and infusions). Herein, the nutritional characterization of C. nobile was performed, and herbal material and its decoction and infusion were submitted to an analysis of phytochemicals and bioactivity evaluation. The antioxidant activity was determined by free radicals scavenging activity, reducing power and inhibition of lipid peroxidation, the antitumour...

  11. Bioactive glasses materials, properties and applications

    CERN Document Server

    Ylänen, Heimo

    2011-01-01

    Due to their biocompatibility and bioactivity, bioactive glasses are used as highly effective implant materials throughout the human body to replace or repair damaged tissue. As a result, they have been in continuous use since shortly after their invention in the late 1960s and are the subject of extensive research worldwide.Bioactive glasses provides readers with a detailed review of the current status of this unique material, its properties, technologies and applications. Chapters in part one deal with the materials and mechanical properties of bioactive glass, examining topics such

  12. Bioactive content, hepatoprotective and antioxidant activities of ...

    African Journals Online (AJOL)

    Bioactive content, hepatoprotective and antioxidant activities of whole plant extract of Micromeria fruticosa (L) Druce ssp Serpyllifolia F Lamiaceae against Carbon tetrachloride-induced hepatotoxicity in mice.

  13. Lipid Based Nanosystems for Curcumin: Past, Present and Future.

    Science.gov (United States)

    Nayak, Aditya P; Mills, Tom; Norton, Ian

    2016-01-01

    Curcumin is one of the principle bioactive compounds used in the ayurvedic medicine system that has the history of over 5000 years for human use. Curcumin an "Indian Gold" is used to treat simple ailments like the common cold to severe life threatening diseases like cancer, and HIV. Though its contribution is immense for the health protection and disease prevention, its clinical use is limited due to its susceptible nature to alkaline pH, high temperature, presence of oxygen and light. Hence it becomes extremely difficult to maintain its bioactivity during processing, storage and consumption. Recent advancements in the application of nanotechnology to curcumin offer an opportunity to enhance its stability, bioactivity and to overcome its pharmacokinetic mismatch. This in turn helps to bridge the gaps that exist between its bench top research data to its clinical findings. Among the various types of nano/micro delivery systems, lipid based delivery systems are well studied and are the best suited delivery systems to enhance the stability and pharmacokinetic profile of curcumin both for pharma and the food application. In the current review, effort will be made to recapitulate the work done in the past to use lipid based delivery systems (liposomes, solid lipid nanoparticles, and emulsions) to enhance the application of curcumin for health promotion and disease prevention. Further, future prospects for the utilization of these lipid-based delivery systems will be discussed in detail.

  14. Bioactivity evolution of the surface functionalized bioactive glasses.

    Science.gov (United States)

    Magyari, Klára; Baia, Lucian; Vulpoi, Adriana; Simon, Simion; Popescu, Octavian; Simon, Viorica

    2015-02-01

    The formation of a calcium phosphate layer on the surface of the SiO2 -CaO-P2 O5 glasses after immersion in simulated body fluid (SBF) generally demonstrates the bioactivity of these materials. Grafting of the surface by chemical bonding can minimize the structural changes in protein adsorbed on the surface. Therefore, in this study our interest was to evaluate the bioactivity and blood biocompatibility of the SiO2 -CaO-P2 O5 glasses after their surface modification by functionalization with aminopropyl-triethoxysilane and/or by fibrinogen. It is shown that the fibrinogen adsorbed on the glass surfaces induces a growing of the apatite-like layer. It is also evidenced that the protein content from SBF influences the growth of the apatite-like layer. Furthermore, the good blood compatibility of the materials after fibrinogen and bovine serum albumin adsorption is proved from the assessment of the β-sheet-β-turn ratio. © 2014 Wiley Periodicals, Inc.

  15. Bioactive compounds from palm fatty acid distillate and crude palm oil

    Science.gov (United States)

    Estiasih, T.; Ahmadi, K.

    2018-03-01

    Crude palm oil (CPO) and palm fatty acid distillate (PFAD) are rich sources of bioactive compounds. PFAD is a by-product of palm oil refinery that produce palm frying oil. Physical refining of palm oil by deodorization produces palm fatty acid distillate. CPO and PFAD contain some bioactive compounds such as vitamin E (tocopherol and tocotrienols), phytosterol, and squalene. Bioactive compounds of CPO and PFAD are vitamin E, phytosterols, and squalene. Vitamin E of CPO and PFAD mainly comprised of tocotrienols and the remaining is tocopherol. Phytosterols of CPO and PFAD contained beta sitosterol, stigmasterol, and campesterol. Tocotrienols and phytosterols of CPO and PFAD, each can be separated to produce tocotrienol rich fraction and phytosterol rich fraction. Tocotrienol rich fraction from PFAD has both antioxidant and cholesterol lowering properties. Bioactive compounds of PFAD silmultaneously have been proven to improve lipid profile, and have hepatoprotector effect, imunomodulator, antioxidant properties, and lactogenic effect in animal test experiment. It is possible to develop separation of bioactive compounds of CPO and PFAD integratively with the other process that utilizes fatty acid.

  16. Electrodiffusion of lipids on membrane surfaces.

    Science.gov (United States)

    Zhou, Y C

    2012-05-28

    Lateral translocation of lipids and proteins is a universal process on membrane surfaces. Local aggregation or organization of lipids and proteins can be induced when the random lateral motion is mediated by the electrostatic interactions and membrane curvature. Although the lateral diffusion rates of lipids on membranes of various compositions are measured and the electrostatic free energies of predetermined protein-membrane-lipid systems can be computed, the process of the aggregation and the evolution to the electrostatically favorable states remain largely undetermined. Here we propose an electrodiffusion model, based on the variational principle of the free energy functional, for the self-consistent lateral drift-diffusion of multiple species of charged lipids on membrane surfaces. Finite sizes of lipids are modeled to enforce the geometrical constraint of the lipid concentration on membrane surfaces. A surface finite element method is developed to appropriate the Laplace-Beltrami operators in the partial differential equations of the model. Our model properly describes the saturation of lipids on membrane surfaces, and correctly predicts that the MARCKS peptide can consistently sequester three multivalent phosphatidylinositol 4,5-bisphosphate lipids through its basic amino acid residues, regardless of a wide range of the percentage of monovalent phosphatidylserine in the membrane.

  17. Radioprotective properties of detoxified lipid A

    International Nuclear Information System (INIS)

    Snyder, S.L.; Walden, T.L. Jr.; Patchen, M.L.

    1985-01-01

    Endotoxic lipopolysaccharide (LPS) has long been known to possess radioprotective properties. Nevertheless, the toxicity of LPS, or its principal bioactive component, Lipid A, has detracted from its potential use as a radioprotectant. Recently, a relatively non-toxic monophosphoryl Lipid A that retains many of the immunobiological properties of native LPS has been prepared from a polyaccharide-deficient and heptoseless Re mutant strain of S. minnesota. The authors conducted experiments that evaluated and compared the radioprotective efficiency of native endotoxin, as well as the mono (detoxified) and diphosphoryl (toxic) forms of Lipid A, in both responder (CD2F1 and C3H/HeN) and non-responder (C3H/HeJ) mice. It has been found that the optimal dose for the mono- and diphosphoryl Lipid A are approximately the same (800 μg/kg in CD2F1 mice), and that both compounds provide maximum protection when administered 24 h before exposure to an LD100 dose of cobalt - 60 gamma radiation. Possible mechanisms for the radioprotective action of detoxified Lipid A are suggested

  18. The role of the vascular endothelial growth factor/vascular endothelial growth factor receptors axis mediated angiogenesis in curcumin-loaded nanostructured lipid carriers induced human HepG2 cells apoptosis

    Directory of Open Access Journals (Sweden)

    Fengling Wang

    2015-01-01

    Full Text Available Background: Curcumin (diferuloylmethane, the active constituent of turmeric extract has potent anti-cancer properties have been demonstrated in hepatocellular carcinoma (HCC. However, its underlying molecular mechanism of therapeutic effects remains unclear. Vascular endothelial growth factor (VEGF and its receptors (VEGFRs have crucial roles in tumor angiogenesis. Purpose: The goal of this study was to investigate the role of the VEGF/VEGFRs mediated angiogenesis during the proliferation and apoptosis of human HepG2 hepatoma cell line and the effect of curcumin-loaded nanostructured lipid carriers (Cur-NLC. Materials and Methods: The proliferation of HepG2 cells was determined by methyl thiazolyl tetrazolium after exposure to Cur-NLC and native curcumin. Apoptosis was quantified by flow cytometry with annexin V-fluorescein isothiocyanate and propidium iodide staining. Cellular internalization of Cur-NLC was observed by fluorescent microscope. The level of VEGF was detected by enzyme-linked immunosorbent assay kits. The expression of VEGFRs was quantified by Western blotting. Results: Cur-NLC was more effective in inhibiting the proliferation and enhancing the apoptosis of HepG2 cells than native curcumin. Fluorescent microscope analysis showed that HepG2 cells internalized Cur-NLC more effectively than native curcumin. Furthermore, Cur-NLC down-regulated the level of VEGF and the expression of VEGFR-2, but had a slight effect on VEGFR-1. Conclusion: These results clearly demonstrated that Cur-NLC was more effective in anti-cancer activity than the free form of curcumin. These studies demonstrate for the 1 st time that Cur-NLC exerts an antitumor effect on HepG2 cells by modulating VEGF/VEGFRs signaling pathway.

  19. In Vivo Inhibition of Lipid Accumulation in Caenorhabditis elegans

    Science.gov (United States)

    Sulistiyani; Purwakusumah, E. P.; Andrianto, D.

    2017-03-01

    This is a preliminary research report on the use of Caenorhabditis elegans as a model to establish anti-obesity screening assay of the natural plant resources. Nematode C. elegans has been used as experimental animal model for understanding lipid accumulation. The objective of this research was to investigate the effect of selected plant extracts on lipid accumulation in C. elegans. Currently no report could be found regarding lipid accumulation in C.elegans treated with ethanolic leaf extracts of jabon merah (Anthocephalus macrophyllus), jati belanda (Guazuma ulmifolia), and Mindi (Melia Azedarach) plants. Lipid accumulation was determined qualitatively using lipid staining method and quantitatively by colorimetry using sulpho-phospho-vanillin reagent. Data showed that lipid accumulation was inhibited up to 72% by extract of M. azedarach, about 35% by both of A. macrophyllus and G. ulmifolia extracts, and up to 25% by orlistat (a synthetic slimming drug). Ethanolic extract of A. macrophyllus, G. ulmifolia, and M. azedarach leaves were shown to inhibit lipid accumulation in C. elegans and M. azedarach leaves extracts was the most effective inhibitor. C.elegans were shown to be an effective model for in vivo lipid accumulation mechanism and potential to be used as a rapid screening assay for bioactive compounds with lipid accumulation inhibitory activity.

  20. Bioactive Components in Fish Venoms

    Science.gov (United States)

    Ziegman, Rebekah; Alewood, Paul

    2015-01-01

    Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

  1. Spontaneous charged lipid transfer between lipid vesicles.

    Science.gov (United States)

    Richens, Joanna L; Tyler, Arwen I I; Barriga, Hanna M G; Bramble, Jonathan P; Law, Robert V; Brooks, Nicholas J; Seddon, John M; Ces, Oscar; O'Shea, Paul

    2017-10-03

    An assay to study the spontaneous charged lipid transfer between lipid vesicles is described. A donor/acceptor vesicle system is employed, where neutrally charged acceptor vesicles are fluorescently labelled with the electrostatic membrane probe Fluoresceinphosphatidylethanolamine (FPE). Upon addition of charged donor vesicles, transfer of negatively charged lipid occurs, resulting in a fluorescently detectable change in the membrane potential of the acceptor vesicles. Using this approach we have studied the transfer properties of a range of lipids, varying both the headgroup and the chain length. At the low vesicle concentrations chosen, the transfer follows a first-order process where lipid monomers are transferred presumably through the aqueous solution phase from donor to acceptor vesicle. The rate of transfer decreases with increasing chain length which is consistent with energy models previously reported for lipid monomer vesicle interactions. Our assay improves on existing methods allowing the study of a range of unmodified lipids, continuous monitoring of transfer and simplified experimental procedures.

  2. Bioactive Glasses in Dentistry: A Review

    Directory of Open Access Journals (Sweden)

    Abbasi Z

    2015-03-01

    Full Text Available Bioactive glasses are silicate-based and can form a strong chemical bond with the tissues. These biomaterials are highly biocompatible and can form a hydroxyapatite layer when implanted in the body or soaked in the simulated body fluid. Due to several disadvantages, conventional glass processing method including melting of glass components, is replaced by sol-gel method with a large number of benefits such as low processing temperature, higher purity and homogeneity and therefore better control of bioactivity. Bioactive glasses have a wide range of applications, particularly in dentistry. These glasses can be used as particulates or monolithic shapes and porous or dense constructs in different applications such as remineralization or hypersensitivity treatment. Some properties of bioactive glasses such as antibacterial properties can be promoted by adding different elements into the glass. Bioactive glasses can also be used to modify different biocompatible materials that need to be bioactive. This study reviews the significant developments of bioactive glasses in clinical application, especially dentistry. Furthermore, we will discuss the field of bioactive glasses from beginning to the current developments, which includes processing methods, applications, and properties of these glasses.

  3. Bioactivity of immobilized hyaluronic acid derivatives regarding protein adsorption and cell adhesion

    DEFF Research Database (Denmark)

    Köwitsch, Alexander; Yang, Yuan; Ma, Ning

    2011-01-01

    with HA on physicochemical surface properties of these substrata and estimates of the quantities of immobilized HA were obtained by different physical methods such as contact angle measurements, ellipsometry, and atomic force microscopy. The bioactivity of aHA and tHA toward their natural binding partner...... affects cell growth and differentiation. A lower number and spreading of cells were observed on HA-modified surfaces compared to amino- and vinyl-terminated glass and silicon surfaces. Immunofluorescence microscopy also revealed that adhesion of fibroblast plated on HA-modified surfaces was mediated...... primarily by HA receptor CD44, indicating that bioactivity of HA was not significantly reduced by chemical modification....

  4. Analysis of Lipoplex Structure and Lipid Phase Changes

    Energy Technology Data Exchange (ETDEWEB)

    Koynova, Rumiana

    2012-07-18

    Efficient delivery of genetic material to cells is needed for tasks of utmost importance in the laboratory and clinic, such as gene transfection and gene silencing. Synthetic cationic lipids can be used as delivery vehicles for nucleic acids and are now considered the most promising nonviral gene carriers. They form complexes (lipoplexes) with the polyanionic nucleic acids. A critical obstacle for clinical application of the lipid-mediated DNA delivery (lipofection) is its unsatisfactory efficiency for many cell types. Understanding the mechanism of lipid-mediated DNA delivery is essential for their successful application, as well as for a rational design and synthesis of novel cationic lipoid compounds for enhanced gene delivery. A viewpoint now emerging is that the critical factor in lipid-mediated transfection is the structural evolution of lipoplexes within the cell, upon interacting and mixing with cellular lipids. In particular, recent studies showed that the phase evolution of lipoplex lipids upon interaction and mixing with membrane lipids appears to be decisive for transfection success: specifically, lamellar lipoplex formulations, which were readily susceptible to undergoing lamellar-nonlamellar phase transition upon mixing with cellular lipids and were found rather consistently associated with superior transfection potency, presumably as a result of facilitated DNA release. Thus, understanding the lipoplex structure and the phase changes upon interacting with membrane lipids is important for the successful application of the cationic lipids as gene carriers.

  5. Laser cladding of bioactive glass coatings.

    Science.gov (United States)

    Comesaña, R; Quintero, F; Lusquiños, F; Pascual, M J; Boutinguiza, M; Durán, A; Pou, J

    2010-03-01

    Laser cladding by powder injection has been used to produce bioactive glass coatings on titanium alloy (Ti6Al4V) substrates. Bioactive glass compositions alternative to 45S5 Bioglass were demonstrated to exhibit a gradual wetting angle-temperature evolution and therefore a more homogeneous deposition of the coating over the substrate was achieved. Among the different compositions studied, the S520 bioactive glass showed smoother wetting angle-temperature behavior and was successfully used as precursor material to produce bioactive coatings. Coatings processed using a Nd:YAG laser presented calcium silicate crystallization at the surface, with a uniform composition along the coating cross-section, and no significant dilution of the titanium alloy was observed. These coatings maintain similar bioactivity to that of the precursor material as demonstrated by immersion in simulated body fluid. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  6. Membrane-spanning lipids for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer

    Science.gov (United States)

    Schwarzmann, Günter; Breiden, Bernadette; Sandhoff, Konrad

    2015-01-01

    A Förster resonance energy transfer-based fusion and transfer assay was developed to study, in model membranes, protein-mediated membrane fusion and intermembrane lipid transfer of fluorescent sphingolipid analogs. For this assay, it became necessary to apply labeled reporter molecules that are resistant to spontaneous as well as protein-mediated intermembrane transfer. The novelty of this assay is the use of nonextractable fluorescent membrane-spanning bipolar lipids. Starting from the tetraether lipid caldarchaeol, we synthesized fluorescent analogs with fluorophores at both polar ends. In addition, we synthesized radioactive glycosylated caldarchaeols. These labeled lipids were shown to stretch through bilayer membranes rather than to loop within a single lipid layer of liposomes. More important, the membrane-spanning lipids (MSLs) in contrast to phosphoglycerides proved to be nonextractable by proteins. We could show that the GM2 activator protein (GM2AP) is promiscuous with respect to glycero- and sphingolipid transfer. Saposin (Sap) B also transferred sphingolipids albeit with kinetics different from GM2AP. In addition, we could unambiguously show that the recombinant activator protein Sap C x His6 induced membrane fusion rather than intermembrane lipid transfer. These findings showed that these novel MSLs, in contrast with fluorescent phosphoglycerolipids, are well suited for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer. PMID:26269359

  7. Membrane-spanning lipids for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer.

    Science.gov (United States)

    Schwarzmann, Günter; Breiden, Bernadette; Sandhoff, Konrad

    2015-10-01

    A Förster resonance energy transfer-based fusion and transfer assay was developed to study, in model membranes, protein-mediated membrane fusion and intermembrane lipid transfer of fluorescent sphingolipid analogs. For this assay, it became necessary to apply labeled reporter molecules that are resistant to spontaneous as well as protein-mediated intermembrane transfer. The novelty of this assay is the use of nonextractable fluorescent membrane-spanning bipolar lipids. Starting from the tetraether lipid caldarchaeol, we synthesized fluorescent analogs with fluorophores at both polar ends. In addition, we synthesized radioactive glycosylated caldarchaeols. These labeled lipids were shown to stretch through bilayer membranes rather than to loop within a single lipid layer of liposomes. More important, the membrane-spanning lipids (MSLs) in contrast to phosphoglycerides proved to be nonextractable by proteins. We could show that the GM2 activator protein (GM2AP) is promiscuous with respect to glycero- and sphingolipid transfer. Saposin (Sap) B also transferred sphingolipids albeit with kinetics different from GM2AP. In addition, we could unambiguously show that the recombinant activator protein Sap C x His6 induced membrane fusion rather than intermembrane lipid transfer. These findings showed that these novel MSLs, in contrast with fluorescent phosphoglycerolipids, are well suited for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  8. Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins[S

    Science.gov (United States)

    Subra, Caroline; Grand, David; Laulagnier, Karine; Stella, Alexandre; Lambeau, Gérard; Paillasse, Michael; De Medina, Philippe; Monsarrat, Bernard; Perret, Bertrand; Silvente-Poirot, Sandrine; Poirot, Marc; Record, Michel

    2010-01-01

    Exosomes are bioactive vesicles released from multivesicular bodies (MVB) by intact cells and participate in intercellular signaling. We investigated the presence of lipid-related proteins and bioactive lipids in RBL-2H3 exosomes. Besides a phospholipid scramblase and a fatty acid binding protein, the exosomes contained the whole set of phospholipases (A2, C, and D) together with interacting proteins such as aldolase A and Hsp 70. They also contained the phospholipase D (PLD) / phosphatidate phosphatase 1 (PAP1) pathway leading to the formation of diglycerides. RBL-2H3 exosomes also carried members of the three phospholipase A2 classes: the calcium-dependent cPLA2-IVA, the calcium-independent iPLA2-VIA, and the secreted sPLA2-IIA and V. Remarkably, almost all members of the Ras GTPase superfamily were present, and incubation of exosomes with GTPγS triggered activation of phospholipase A2 (PLA2)and PLD2. A large panel of free fatty acids, including arachidonic acid (AA) and derivatives such as prostaglandin E2 (PGE2) and 15-deoxy-Δ12,14-prostaglandinJ2 (15-d PGJ2), were detected. We observed that the exosomes were internalized by resting and activated RBL cells and that they accumulated in an endosomal compartment. Endosomal concentrations were in the micromolar range for prostaglandins; i.e., concentrations able to trigger prostaglandin-dependent biological responses. Therefore exosomes are carriers of GTP-activatable phospholipases and lipid mediators from cell to cell. PMID:20424270

  9. Improvement of Neutral Lipid and Polyunsaturated Fatty Acid Biosynthesis by Overexpressing a Type 2 Diacylglycerol Acyltransferase in Marine Diatom Phaeodactylum tricornutum

    Directory of Open Access Journals (Sweden)

    Ying-Fang Niu

    2013-11-01

    Full Text Available Microalgae have been emerging as an important source for the production of bioactive compounds. Marine diatoms can store high amounts of lipid and grow quite quickly. However, the genetic and biochemical characteristics of fatty acid biosynthesis in diatoms remain unclear. Glycerophospholipids are integral as structural and functional components of cellular membranes, as well as precursors of various lipid mediators. In addition, diacylglycerol acyltransferase (DGAT is a key enzyme that catalyzes the last step of triacylglyceride (TAG biosynthesis. However, a comprehensive sequence-structure and functional analysis of DGAT in diatoms is lacking. In this study, an isoform of diacylglycerol acyltransferase type 2 of the marine diatom Phaeodactylum tricornutum was characterized. Surprisingly, DGAT2 overexpression in P. tricornutum stimulated more oil bodies, and the neutral lipid content increased by 35%. The fatty acid composition showed a significant increase in the proportion of polyunsaturated fatty acids; in particular, EPA was increased by 76.2%. Moreover, the growth rate of transgenic microalgae remained similar, thereby maintaining a high biomass. Our results suggest that increased DGAT2 expression could alter fatty acid profile in the diatom, and the results thus represent a valuable strategy for polyunsaturated fatty acid production by genetic manipulation.

  10. Peptides: Production, bioactivity, functionality, and applications

    DEFF Research Database (Denmark)

    Hajfathalian, Mona; Ghelichi, Sakhi; García Moreno, Pedro Jesús

    2017-01-01

    Production of peptides with various effects from proteins of different sources continues to receive academic attention. Researchers of different disciplines are putting increasing efforts to produce bioactive and functional peptides from different sources such as plants, animals, and food industry...... by-products. The aim of this review is to introduce production methods of hydrolysates and peptides and provide a comprehensive overview of their bioactivity in terms of their effects on immune, cardiovascular, nervous, and gastrointestinal systems. Moreover, functional and antioxidant properties...... of hydrolysates and isolated peptides are reviewed. Finally, industrial and commercial applications of bioactive peptides including their use in nutrition and production of pharmaceuticals and nutraceuticals are discussed....

  11. Nutrients and bioactive substances in aquatic organisms

    International Nuclear Information System (INIS)

    Devadasan, K.; Mukundan, M.K.; Antony, P.D.; Viswanathan Nair, P.G.; Perigreen, P.A.; Joseph, Jose

    1994-01-01

    The International Symposium on Nutrients and Bioactive Substances in Aquatic Organisms, was held during 16-17 September 1993 by the Society of Fisheries Technologists (India) to review the progress of research in this area in India and elsewhere. The papers presented indicate that scientific productivity in this field is substantial and that some of the bioactive materials isolated from aquatic organisms have potential application in human health, nutrition and therapy. The symposium focussed attention on toxicants, nutrients and bioactive substances in aquatic organisms in general, and also on pollution of aquatic systems due to thermal effluents. Paper relevant to INIS database is indexed separately. (M.K.V.)

  12. Bioactivities and Health Benefits of Wild Fruits

    Directory of Open Access Journals (Sweden)

    Ya Li

    2016-08-01

    Full Text Available Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we review current knowledge about the bioactivities and health benefits of wild fruits, which is valuable for the exploitation and utilization of wild fruits.

  13. Bioavailability of Isothiocyanates From Broccoli Sprouts in Protein, Lipid, and Fiber Gels

    OpenAIRE

    Oliviero, Teresa; Lamers, Simone; Capuano, Edoardo; Dekker, Matthijs; Verkerk, Ruud

    2018-01-01

    Scope: Optimization of bioavailability of dietary bioactive health-beneficial compounds is as important as increasing their concentration in foods. The aim of this study is to explore the change in bioavailability of isothiocyanates (ITCs) in broccoli sprouts incorporated in protein, fiber, and lipid gels. Methods and results: Five participants took part in a cross-over study and collected timed urine samples up to 24 h after consumption of proteins, dietary fibers, and lipid gels containing ...

  14. Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage

    International Nuclear Information System (INIS)

    Istrati, D.; Lacatusu, I.; Bordei, N.; Badea, G.; Oprea, O.; Stefan, L.M.; Stan, R.; Badea, N.; Meghea, A.

    2016-01-01

    The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to − 45 mV) and displayed average sizes of 70 nm to 140 nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract–bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. - Highlights: • Safety phyto-mediated nanostructured carriers (NLC) based on two kinds of bioactives • Carrot extract incorporation into nanostructured carriers ranged from 78 to 88.3%. • High antioxidant activity of NLC by scavenging up to 98% free oxygen radicals • Extract entrapment represents a viable way for an equilibrated release of carotenoids. • Remarkable regenerative effect of L929 cell, with a proliferation of 133.4%

  15. Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Istrati, D.; Lacatusu, I.; Bordei, N.; Badea, G.; Oprea, O. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Stefan, L.M. [National Institute of Research and Development for Biological Sciences, Splaiul Independentei Street No. 296, 060031 Bucharest (Romania); Stan, R. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Badea, N., E-mail: nicoleta.badea@gmail.com [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Meghea, A. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania)

    2016-07-01

    The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to − 45 mV) and displayed average sizes of 70 nm to 140 nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract–bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. - Highlights: • Safety phyto-mediated nanostructured carriers (NLC) based on two kinds of bioactives • Carrot extract incorporation into nanostructured carriers ranged from 78 to 88.3%. • High antioxidant activity of NLC by scavenging up to 98% free oxygen radicals • Extract entrapment represents a viable way for an equilibrated release of carotenoids. • Remarkable regenerative effect of L929 cell, with a proliferation of 133.4%.

  16. Sol-gel derived porous bioactive nanocomposites: Synthesis and in vitro bioactivity

    Science.gov (United States)

    Shankhwar, Nisha; Kothiyal, G. P.; Srinivasan, A.

    2013-06-01

    Porous bioactive composites consisting of SiO2-CaO-Na2O-P2O5 bioactive glass-ceramic and synthetic water soluble polymer Polyvinylpyrrolidone [PVP (C6H9NO)n, MW˜40000 g/mol] have been synthesized by sol-gel route. As-prepared polymeric composites were characterized by X-ray diffraction (XRD) technique. Two major bone mineral phases, viz., hydroxyapatite [Ca10(PO4)6(OH)2] and wollastonite [calcium silicate (CaSiO3)] have been identified in the XRD patterns of the composites. Presence of these bone minerals indicates the bioactive nature of the composites. In vitro bioactivity tests confirm bioactivity in the porous composites. The flexibility offered by these bioactive polymer composites is advantageous for its application as implant material.

  17. Nerve growth factor expression by PLG-mediated lipofection.

    Science.gov (United States)

    Whittlesey, Kevin J; Shea, Lonnie D

    2006-04-01

    Biomaterials capable of efficient gene delivery provide a fundamental tool for basic and applied research models, such as promoting neural regeneration. We developed a system for the encapsulation and sustained release of plasmid DNA complexed with a cationic lipid and investigated their efficacy using in vitro models of neurite outgrowth. Sustained lipoplex release was obtained for up to 50 days, with rates controlled by the fabrication conditions. Released lipoplexes retained their activity, transfecting 48.2+/-8.3% of NIH3T3 cells with luciferase activity of 3.97x10(7)RLU/mg. Expression of nerve growth factor (NGF) was employed in two models of neurite outgrowth: PC12 and primary dorsal root ganglia (DRG) co-culture. Polymer-mediated lipofection of PC12 produced bioactive NGF, eliciting robust neurite outgrowth. An EGFP/NGF dual-expression vector identified transfected cells (GFP-positive) while neurite outgrowth verified NGF secretion. A co-culture model examined the ability of NGF secretion by an accessory cell population to stimulate DRG neurite outgrowth. Polymer-mediated transfection of HEK293T with an NGF-encoding plasmid induced outgrowth by DRG neurons. This system could be fabricated as implants or nerve guidance conduits to support cellular and tissue regeneration. Combining this physical support with the ability to locally express neurotrophic factors will potentiate regeneration in nerve injury and disease models.

  18. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities.

    Science.gov (United States)

    Hayes, Maria; Tiwari, Brijesh K

    2015-09-17

    Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.

  19. Silicon Utilizing Microbial Bioactivities in the Biosphere

    Science.gov (United States)

    Sen, M. M.; Das, S.

    2012-12-01

    potential as a source of biomass for the production of biofuels, due to their high growth rates and high cellular lipid content. Petroleum pollutant degradation can also be done by these organisms-Achanthes minutissima has degradable effects involving petroleum hydocarbons. Stephanopyxis turris a silicon utilizing organism releases a blend of chlorinated C8 hydrocarbons. This adds a fundamentally new pathway to the limited set of halogenating enzymatic activities known from nature. Many silicon utilizing organisms can produce PUFA from saturated fatty acids which ultimately produce many important bioactive chemicals like hormosirene, finaverrene, heptadienal, dietyopterene, cystophorene, decadienal. Trienoic acid, octadiene and many other important agents. Similarly terpenoid biosynthetic pathway is activated by them with formation of diterpenoids, sesterpenoids, triterpenoids and sterols.

  20. A close collaboration of chitosan with lipid colloidal carriers for drug delivery applications.

    Science.gov (United States)

    Bugnicourt, Loïc; Ladavière, Catherine

    2017-06-28

    Chitosan and lipid colloids have separately shown a growing interest in the field of drug delivery applications. Their success is mainly due to their interesting physicochemical behaviors, as well as their biological properties such as bioactivity and biocompatibility. While chitosan is a well-known cationic polysaccharide with the ability to strongly interact with drugs and biological matrices through mainly electrostatic interactions, lipid colloids are carriers particularly recognized for the drug vectorization. In recent years, the combination of both entities has been considered because it offers new systems which gather the advantages of each of them to efficiently deliver various types of bioactive species. The purpose of this review is to describe these associations between chemically-unmodified chitosan chains (solubilized or dispersed) and lipid colloids (as nanoparticles or organized in lipid layers), as well as their potential in the drug delivery area so far. Three assemblies have mainly been reported in the literature: i) lipid nanoparticles (solid lipid nanoparticles or nanostructured lipid carriers) coated with chitosan chains, ii) lipid vesicles covered with chitosan chains, and iii) chitosan chains structured in nanoparticles with a lipid coating. Their elaboration processes, their physicochemical characterization, and their biological studies are detailed and discussed herein. The different bioactive species (drugs and bio(macro)molecules) incorporated in these assemblies, their maximal incorporation efficiency, and their loading capacity are also presented. This review reveals the versatility of these assemblies. Depending on the organization of lipids (i.e., nanoparticles or vesicles) and the state of polymer chains (i.e., solubilized or dispersed under the form of nanoparticles), a large variety of drugs can be successfully incorporated, and various routes of administration can be considered. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Beebread from Apis mellifera and Apis dorsata. Comparative Chemical Composition and Bioactivity

    Directory of Open Access Journals (Sweden)

    Otilia BOBIS

    2017-05-01

    Full Text Available Beebread is a valuable bee product, both for bee nutrition and for humans. The high nutritional and bioactive properties of beebread were evaluated by chemical composition analysis of beebread from Apis mellifera and Apis dorsata. Bee bread harvested from Romania and India, coming from Apis mellifera and Apis dorsata bees, were evaluated for their chemical composition. Analyses were made in APHIS Laboratory from USAMV Cluj, using validated methods for bee products. Lipids were determined by the Soxhlet extraction method, total protein content was determined by Kjehldahl method, sugar spectrum was determined by high performance liquid chromatography with refractive index detection (HPLC-IR. Water content of beebread samples were situated between 11.45 and 16.46%, total protein content between 16.84 and 19.19% and total lipids between 6.36 and 13.47%.  Beebread has high bioactive properties which can be expressed as antioxidant and/or antibacterial activity. Chemical composition and bioactive properties of beebread is influenced by floral origin of the pollen which the bees collect and place in combs for fermentation. Also the climatic conditions have an important role in developing different fermentation compounds, that may act as antioxidants or antibacterial agents.

  2. Flaxseed Oil Alleviates Chronic HFD-Induced Insulin Resistance through Remodeling Lipid Homeostasis in Obese Adipose Tissue.

    Science.gov (United States)

    Yu, Xiao; Tang, Yuhan; Liu, Peiyi; Xiao, Lin; Liu, Liegang; Shen, Ruiling; Deng, Qianchun; Yao, Ping

    2017-11-08

    Emerging evidence suggests that higher circulating long-chain n-3 polyunsaturated fatty acids (n-3PUFA) levels were intimately associated with lower prevalence of obesity and insulin resistance. However, the understanding of bioactivity and potential mechanism of α-linolenic acid-rich flaxseed oil (ALA-FO) against insulin resistance was still limited. This study evaluated the effect of FO on high-fat diet (HFD)-induced insulin resistance in C57BL/6J mice focused on adipose tissue lipolysis. Mice after HFD feeding for 16 weeks (60% fat-derived calories) exhibited systemic insulin resistance, which was greatly attenuated by medium dose of FO (M-FO), paralleling with differential accumulation of ALA and its n-3 derivatives across serum lipid fractions. Moreover, M-FO was sufficient to effectively block the metabolic activation of adipose tissue macrophages (ATMs), thereby improving adipose tissue insulin signaling. Importantly, suppression of hypoxia-inducible factors HIF-1α and HIF-2α were involved in FO-mediated modulation of adipose tissue lipolysis, accompanied by specific reconstitution of n-3PUFA within adipose tissue lipid fractions.

  3. Synthesis and bioactive evaluations of novel benzotriazole ...

    Indian Academy of Sciences (India)

    Synthesis and bioactive evaluations of novel benzotriazole compounds as ... School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, .... −3 mol/L) was prepared by dissolving its solid in doubly distilled water.

  4. Advances on Bioactive Polysaccharides from Medicinal Plants.

    Science.gov (United States)

    Xie, Jian-Hua; Jin, Ming-Liang; Morris, Gordon A; Zha, Xue-Qiang; Chen, Han-Qing; Yi, Yang; Li, Jing-En; Wang, Zhi-Jun; Gao, Jie; Nie, Shao-Ping; Shang, Peng; Xie, Ming-Yong

    2016-07-29

    In recent decades, the polysaccharides from the medicinal plants have attracted a lot of attention due to their significant bioactivities, such as anti-tumor activity, antioxidant activity, anticoagulant activity, antidiabetic activity, radioprotection effect, anti-viral activity, hypolipidemic and immunomodulatory activities, which make them suitable for medicinal applications. Previous studies have also shown that medicinal plant polysaccharides are non-toxic and show no side effects. Based on these encouraging observations, most researches have been focusing on the isolation and identification of polysaccharides, as well as their bioactivities. A large number of bioactive polysaccharides with different structural features and biological effects from medicinal plants have been purified and characterized. This review provides a comprehensive summary of the most recent developments in physiochemical, structural features and biological activities of bioactive polysaccharides from a number of important medicinal plants, such as polysaccharides from Astragalus membranaceus, Dendrobium plants, Bupleurum, Cactus fruits, Acanthopanax senticosus, Angelica sinensis (Oliv.) Diels, Aloe barbadensis Miller, and Dimocarpus longan Lour. Moreover, the paper has also been focused on the applications of bioactive polysaccharides for medicinal applications. Recent studies have provided evidence that polysaccharides from medicinal plants can play a vital role in bioactivities. The contents and data will serve as a useful reference material for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

  5. Antioxidant Potential and Modulatory Effects of Restructured Lipids from the Amazonian Palms on Liver Cells

    Directory of Open Access Journals (Sweden)

    Andrea de Oliveira Falcão

    2017-01-01

    Full Text Available Enzymatic interesterification is used to manipulate oil and fat in order to obtain improved restructured lipids with desired technological properties. However, with raw materials containing significant amounts of bioactive compounds, the influence of this enzymatic process on the bioactivity of the final product is still not clear. Thus, the aim of this study is to evaluate the antioxidant potential and modulatory effects of two raw materials from the Amazonian area, buriti oil and murumuru fat, before and after lipase interesterification, on human hepatoma cells (HepG2. The results indicate that minor bioactive compounds naturally found in the raw materials and their antioxidant capacity are preserved after enzymatic interesterification, and that the restructured lipids modulate HepG2 endogenous antioxidant enzyme.

  6. Microalgal lipids biochemistry and biotechnological perspectives.

    Science.gov (United States)

    Bellou, Stamatia; Baeshen, Mohammed N; Elazzazy, Ahmed M; Aggeli, Dimitra; Sayegh, Fotoon; Aggelis, George

    2014-12-01

    . Therefore, algal production systems need to be improved and harvesting systems need to be more effective in order for their industrial applications to become more competitive and economically viable. Besides, a reduction of the production cost of microalgal lipids can be achieved by combining lipid production with other commercial applications. The combined production of bioactive products and lipids, when possible, can support the commercial viability of both processes. Hydrophobic compounds can be extracted simultaneously with lipids and then purified, while hydrophilic compounds such as proteins and sugars may be extracted from the defatted biomass. The microalgae also have applications in environmental biotechnology since they can be used for bioremediation of wastewater and to monitor environmental toxicants. Algal biomass produced during wastewater treatment may be further valorized in the biofuel manufacture. It is anticipated that the high microalgal lipid potential will force research towards finding effective ways to manipulate biochemical pathways involved in lipid biosynthesis and towards cost effective algal cultivation and harvesting systems, as well. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Ceramide in lipid emulsions used in parenteral nutrition: an innocent bystander?

    NARCIS (Netherlands)

    Groener, Johanna E.; Serlie, Mireille J.; Poppema, Aldi; Mirzaian, Mina; Aerts, Johannes M.

    2011-01-01

    Parenteral nutrition-associated liver disease is a prevalent and severe complication of long term parenteral nutrition. We present here for the first time data on the presence of ceramide, a bioactive compound involved in a variety of metabolic processes, in different lipid emulsions used in

  8. Polymerization kinetics of experimental bioactive composites containing bioactive glass.

    Science.gov (United States)

    Par, Matej; Tarle, Zrinka; Hickel, Reinhard; Ilie, Nicoleta

    2018-06-21

    To investigate the polymerization kinetics and the degree of conversion (DC) of experimental resin composites with varying amount of bioactive glass 45S5 (BG). Experimental resin composites based on a photo-curable Bis-GMA/TEGDMA resin system were prepared. The composite series contained 0, 5, 10, 20, and 40 wt% of BG and reinforcing fillers up to the total filler amount of 70 wt%. Composite specimens were light cured with 1,219 mW/cm 2 for 20 or 40 s and their DC was monitored during 5 min at the data collection rate of 2 s -1 using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The 5-min DC values for experimental composites were in the range of 42.4-55.9% and 47.3-57.9% for curing times of 20 and 40 s, respectively. The differences in the 5-min DC between curing times of 20 s or 40 s became more pronounced in materials with higher BG amount. Within both curing times, a decreasing trend of the 5-min DC values was observed with the increasing percentage of BG fillers. The maximum polymerization rate also decreased consistently with the increasing BG amount. Unsilanized BG fillers showed a dose-dependent inhibitory effect on polymerization rate and the DC. Extending the curing time from 20 to 40 s showed a limited potential to improve the DC of composites with higher BG amount. The observed inhibitory effect of BG fillers on the polymerization of resin composites may have a negative influence on mechanical properties and biocompatibility. Copyright © 2018. Published by Elsevier Ltd.

  9. Resistance of Gram-positive bacteria to nisin is not determined by Lipid II levels

    NARCIS (Netherlands)

    Kramer, NE; Smid, EJ; Kok, J; de Kruijff, B; Kuipers, OP; Breukink, E; Kramer, Naomi E.; Smid, Eddy J.

    2004-01-01

    Lipid II is essential for nisin-mediated pore formation at nano-molar concentrations. We tested whether nisin resistance could result from different Lipid II levels, by comparing the maximal Lipid II pool in Micrococcus flavus (sensitive) and Listeria monocytogenes (relatively insensitive) and their

  10. Lipid exchange by ultracentrifugation

    DEFF Research Database (Denmark)

    Drachmann, Nikolaj Düring; Olesen, Claus

    2014-01-01

    , and the complex interplay between the lipids and the P-type ATPases are still not well understood. We here describe a robust method to exchange the majority of the lipids surrounding the ATPase after solubilisation and/or purification with a target lipid of interest. The method is based on an ultracentrifugation...... step, where the protein sample is spun through a dense buffer containing large excess of the target lipid, which results in an approximately 80-85 % lipid exchange. The method is a very gently technique that maintains protein folding during the process, hence allowing further characterization...

  11. In vitro bioactivity of polymer matrices reinforced with a bioactive glass phase

    Directory of Open Access Journals (Sweden)

    Oréfice Rodrigo L.

    2000-01-01

    Full Text Available Composites that can mimic the in vitro bioactive behavior of bioactive glasses were designed to fulfill two main features of bioactive glasses that are responsible for their high bond-to-bone rates: (1 capability of providing ions such as calcium and phosphate to the nearby environment and (2 ideal surface structure that allows fast heterogeneous precipitation of hydroxy-carbonate-apatite (HCA. The novel composites were prepared by incorporating bioactive glass particles into polymer matrices. The in vitro bioactivity test was performed by introducing samples into a buffered solution as well as into a simulated body fluid solution. FTIR was used to evaluate the kinetics of HCA (hydroxy-carbonate-apatite precipitation. The results showed that the obtained composites can supply ions, such as silicates and phosphates in rates and concentrations comparable or superior than bulk bioactive glasses. Moreover, the surface chemistry of the composites was altered to mimic the surface of bioactive glasses. It was demonstrated that the in vitro bioactivity of the composites was enhanced by chemically modifying polymer surfaces through the introduction of special alkoxysilane groups.

  12. Bioactive metabolites of docosahexaenoic acid

    Czech Academy of Sciences Publication Activity Database

    Kuda, Ondřej

    2017-01-01

    Roč. 136, May (2017), s. 12-20 ISSN 0300-9084 R&D Projects: GA ČR(CZ) GA16-04859S; GA MZd(CZ) NV16-29182A Institutional support: RVO:67985823 Keywords : DHA * specialized proresolving mediators * FAHFA * DHEA * N-acyl amides * omega-3 PUFA Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 3.112, year: 2016

  13. Lipid Structure in Triolein Lipid Droplets

    DEFF Research Database (Denmark)

    Chaban, Vitaly V; Khandelia, Himanshu

    2014-01-01

    of a mass of hydrophobic lipid esters coved by phospholipid monolayer. The small size and unique architecture of LDs makes it complicated to study LD structure by modern experimental methods. We discuss coarse-grained molecular dynamics (MD) simulations of LD formation in systems containing 1-palmitoyl-2...... to coarse-grained simulations, the presence of PE lipids at the interface has a little impact on distribution of components and on the overall LD structure. (4) The thickness of the lipid monolayer at the surface of the droplet is similar to the thickness of one leaflet of a bilayer. Computer simulations......Lipid droplets (LDs) are primary repositories of esterified fatty acids and sterols in animal cells. These organelles originate on the lumenal or cytoplasmic side of endoplasmic reticulum (ER) membrane and are released to the cytosol. In contrast to other intracellular organelles, LDs are composed...

  14. Encapsulating fatty acid esters of bioactive compounds in starch

    Science.gov (United States)

    Lay Ma, Ursula Vanesa

    . However, only retinyl palmitate formed a complex with amylopectin. In general, ascorbyl palmitate resulted in the highest complexation, followed by retinyl palmitate and phytosterol ester. The presence of native lipids in Hylon VII starch did not inhibit complex formation. On the contrary, native lipids appear to increase the complexation yield and thermal stability of the starch-fatty acid ester inclusion complexes, possibly due to the formation of ternary complexes. From the three fatty acid esters studied, only ascorbyl palmitate was entrapped in starch spherulites. Various structures including round spherulites, various sizes of torus-shape spherulites, non-spherulitic birefringent and non-birefringent particles, "balloon" morphologies, and gel-like material were formed depending on processing conditions. However, only the torus-shape spherulites, and some non-spherulitic birefringent and non-birefringent particles showed ascorbyl palmitate entrapment. The % yield of the precipitate increased with higher % of added Hylon VII, and decreased with higher heating temperature and faster cooling rates. The amount of entrapped ascorbyl palmitate in the starch precipitate seems to be governed by the amount of this compound added during processing. This study showed that starch can form inclusion complexes with fatty acid esters which may be used for the delivery of certain bioactive molecules. In addition, encapsulation of fatty acid esters in starch spherulites may be a good potential delivery system for water soluble bioactive molecules. However, further research is necessary to gain a better understanding of the type of molecules that can be entrapped in starch spherulites, and the factors affecting spherulitic crystallization and bioactive compound entrapment.

  15. Synthetic biology approaches: Towards sustainable exploitation of marine bioactive molecules.

    Science.gov (United States)

    Seghal Kiran, G; Ramasamy, Pasiyappazham; Sekar, Sivasankari; Ramu, Meenatchi; Hassan, Saqib; Ninawe, A S; Selvin, Joseph

    2018-06-01

    The discovery of genes responsible for the production of bioactive metabolites via metabolic pathways combined with the advances in synthetic biology tools, has allowed the establishment of numerous microbial cell factories, for instance the yeast cell factories, for the manufacture of highly useful metabolites from renewable biomass. Genome mining and metagenomics are two platforms provide base-line data for reconstruction of genomes and metabolomes which is based in the development of synthetic/semi-synthetic genomes for marine natural products discovery. Engineered biofilms are being innovated on synthetic biology platform using genetic circuits and cell signalling systems as represillators controlling biofilm formation. Recombineering is a process of homologous recombination mediated genetic engineering, includes insertion, deletion or modification of any sequence specifically. Although this discipline considered new to the scientific domain, this field has now developed as promising endeavor on the accomplishment of sustainable exploitation of marine natural products. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. CaMKII-MEDIATED PHOSPHORYLATION OF THE BOMBYX MORI LIPID STORAGE DROPLET PROTEIN-1 (BmLsd1), AN INSECT PAT FAMILY PROTEIN, IS ESSENTIAL FOR SILKMOTH SEX PHEROMONE BIOSYNTHESIS

    Science.gov (United States)

    The structurally-related members of the PAT family of proteins, which are so name based on similarity amongst perilipin, adipophilin/adipocyte differentiation-related protein (ADRP), and tail-interacting protein of 47 kilodaltons (TIP47), are cytoplasmic lipid droplet (LD)-associated proteins charac...

  17. Hormone signaling linked to silkmoth sex pheromone biosynthesis involves Ca2+/calmodulin-dependent protein kinase II-mediated phosphorylation of the insect PAT family protein Bombyx mori lipid storage droplet protein-1(BmLsd)

    Science.gov (United States)

    The structurally-related members of the PAT family of proteins, which are so name based on similarity amongst perilipin, adipophilin/adipocyte differentiation-related protein (ADRP), and tail-interacting protein of 47 kilodaltons (TIP47), are cytoplasmic lipid droplet (LD)-associated proteins charac...

  18. Microencapsulation of bioactives for food applications.

    Science.gov (United States)

    Dias, Maria Inês; Ferreira, Isabel C F R; Barreiro, Maria Filomena

    2015-04-01

    Health issues are an emerging concern to the world population, and therefore the food industry is searching for novel food products containing health-promoting bioactive compounds, with little or no synthetic ingredients. However, there are some challenges in the development of functional foods, particularly in which the direct use of some bioactives is involved. They can show problems of instability, react with other food matrix ingredients or present strong odour and/or flavours. In this context, microencapsulation emerges as a potential approach to overcome these problems and, additionally, to provide controlled or targeted delivery or release. This work intends to contribute to the field of functional food development by performing a comprehensive review on the microencapsulation methods and materials, the bioactives used (extracts and isolated compounds) and the final application development. Although several studies dealing with microencapsulation of bioactives exist, they are mainly focused on the process development and the majority lack proof of concept for final applications. These factors, together with the lack of regulation, in Europe and in the United States, delay the development of new functional foods and, consequently, their market entry. In conclusion, the potential of microencapsulation to protect bioactive compounds ensuring their bioavailability is shown, but further studies are required, considering both its applicability and incentives by regulatory agencies.

  19. Peptidome characterization and bioactivity analysis of donkey milk.

    Science.gov (United States)

    Piovesana, Susy; Capriotti, Anna Laura; Cavaliere, Chiara; La Barbera, Giorgia; Samperi, Roberto; Zenezini Chiozzi, Riccardo; Laganà, Aldo

    2015-04-24

    Donkey milk is an interesting commercial product for its nutritional values, which make it the most suitable mammalian milk for human consumption, and for the bioactivity associated with it and derivative products. To further mine the characterization of donkey milk, an extensive peptidomic study was performed. Two peptide purification strategies were compared to remove native proteins and lipids and enrich the peptide fraction. In one case the whole protein content was precipitated by organic solvent using cold acetone. In the other one the precipitation of the most abundant milk proteins, caseins, was performed under acidic conditions by acetic acid at pH4.6, instead. The procedures were compared and proved to be partially complementary. Considered together they provided 1330 peptide identifications for donkey milk, mainly coming from the most abundant proteins in milk. The bioactivity of the isolated peptides was also investigated, both by angiotensin-converting-enzyme inhibitory and antioxidant activity assays and by bioinformatics, proving that the isolated peptides did have the tested biological activities. The rationale behind this study is that peptides in food matrices often play an important biological role and, despite the extensive study of the protein composition of different samples, they remain poorly characterized. In fact, in a typical shotgun proteomics study endogenous peptides are not properly characterized. In proteomics workflows one limiting point is the isolation process: if it is specific for the purification of proteins, it often comprises a precipitation step which aims at isolating pure protein pellets and remove unwonted interferent compounds. In this way endogenous peptides, which are not effectively precipitated as well as proteins, are removed too and not analyzed at the end of the process. Moreover, endogenous peptides do often originate from precursor proteins, but in phenomena which are independent of the shotgun digestion

  20. Microbial biotransformation of bioactive flavonoids.

    Science.gov (United States)

    Cao, Hui; Chen, Xiaoqing; Jassbi, Amir Reza; Xiao, Jianbo

    2015-01-01

    The bioactive flavonoids are considered as the most important phytochemicals in food, which exert a wide range of biological benefits for human being. Microbial biotransformation strategies for production of flavonoids have attracted considerable interest because they allow yielding novel flavonoids, which do not exist in nature. In this review, we summarize the existing knowledge on the production and biotransformation of flavonoids by various microbes. The main reactions during microbial biotransformation are hydroxylation, dehydroxylation, O-methylation, O-demethylation, glycosylation, deglycosylation, dehydrogenation, hydrogenation, C ring cleavage of the benzo-γ-pyrone system, cyclization, and carbonyl reduction. Cunninghamella, Penicillium, and Aspergillus strains are very popular to biotransform flavonoids and they can perform almost all the reactions with excellent yields. Aspergillus niger is one of the most applied microorganisms in the flavonoids' biotransformation; for example, A. niger can transfer flavanone to flavan-4-ol, 2'-hydroxydihydrochalcone, flavone, 3-hydroxyflavone, 6-hydroxyflavanone, and 4'-hydroxyflavanone. The hydroxylation of flavones by microbes usually happens on the ortho position of hydroxyl group on the A ring and C-4' position of the B ring and microbes commonly hydroxylate flavonols at the C-8 position. The microorganisms tend to hydroxylate flavanones at the C-5, 6, and 4' positions; however, for prenylated flavanones, dihydroxylation often takes place on the C4α=C5α double bond on the prenyl group (the side chain of A ring). Isoflavones are usually hydroxylated at the C-3' position of the B ring by microorganisms. The microbes convert flavonoids to their 7-O-glycosides and 3-O-glycosides (when flavonoids have a hydroxyl moiety at the C-3 position). The demethylation of multimethoxyl flavonoids by microbes tends to happen at the C-3' and C-4' positions of the B ring. Multimethoxyl flavanones and isoflavone are demethylated at

  1. Membrane Contact Sites: Complex Zones for Membrane Association and Lipid Exchange

    OpenAIRE

    Evan Quon; Christopher T. Beh

    2016-01-01

    Lipid transport between membranes within cells involves vesicle and protein carriers, but as agents of nonvesicular lipid transfer, the role of membrane contact sites has received increasing attention. As zones for lipid metabolism and exchange, various membrane contact sites mediate direct associations between different organelles. In particular, membrane contact sites linking the plasma membrane (PM) and the endoplasmic reticulum (ER) represent important regulators of lipid and ion transfer...

  2. Effect of a bioactive curcumin derivative on DPPC membrane: A DSC and Raman spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Gardikis, Kostantinos [Department of Pharm. Technology, School of Pharmacy, University of Athens, Athens (Greece); Hatziantoniou, Sophia [Department of Pharm. Technology, School of Pharmacy, University of Athens, Athens (Greece); Viras, Kyriakos [Laboratory of Physical Chemistry, Department of Chemistry, University of Athens, Athens (Greece); Demetzos, Costas [Department of Pharm. Technology, School of Pharmacy, University of Athens, Athens (Greece)]. E-mail: demetzos@pharm.uoa.gr

    2006-08-01

    Interactions of dimethoxycurcumin (1) a lipophilic bioactive curcumin derivative with dipalmitoyl phosphatidylcholine (DPPC) were investigated. The thermodynamic changes caused by (1) and its location into DPPC lipid bilayers were monitored by differential scanning calorimetry and Raman spectroscopy. The results reveal that (1) influences the thermotropic properties of DPPC lipid membrane causing abolition of the pretransition and broadening of the phase-transition profile and slightly decreases the T {sub m} at increasing concentrations. The Raman height intensity ratios of the peaks I {sub 2935/2880}, I {sub 2844/2880} and I {sub 1090/1130} are representative of the interaction of (1) with the alkyl chains and furnish information about the ratio between disorder and order that exists in the conformation of the alkyl chain. The intensity changes of the peak at 715 cm{sup -1} indicates interaction between the choline head group and (1). The Raman spectroscopy results are in agreement with the thermal analysis results. Biologically active lipophilic molecules such as (1) should be studied in terms of their interaction with lipid bilayers prior to the development of advanced lipid carrier systems such as liposomes. The results of these studies provide information on the membrane integrity and physicochemical properties that are essential for the rational design lipidic drug delivery systems.

  3. Enhanced bioactivity, biocompatibility and mechanical behavior of strontium substituted bioactive glasses.

    Science.gov (United States)

    Arepalli, Sampath Kumar; Tripathi, Himanshu; Hira, Sumit Kumar; Manna, Partha Pratim; Pyare, Ram; S P Singh

    2016-12-01

    Strontium contained biomaterials have been reported as a potential bioactive material for bone regeneration, as it reduces bone resorption and stimulates bone formation. In the present investigation, the bioactive glasses were designed to partially substitute SrO for SiO2 in Na2O-CaO-SrO-P2O5-SiO2 system. This work demonstrates that the substitution of SrO for SiO2 has got significant benefit than substitution for CaO in the bioactive glass. Bioactivity was assessed by the immersion of the samples in simulated body fluid for different intervals. The formation of hydroxy carbonate apatite layer was identified by X-ray diffractometry, scanning electron microscopy (SEM) and energy dispersive spectroscopy. The elastic modulus of the bioactive glasses was measured and found to increase with increasing SrO for SiO2. The blood compatibility of the samples was evaluated. In vitro cell culture studies of the samples were performed using human osteosarcoma U2-OS cell lines and found a significant improvement in cell viability and proliferation. The investigation showed enhancement in bioactivity, mechanical and biological properties of the strontia substituted for silica in glasses. Thus, these bioactive glasses would be highly potential for bone regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Enhanced bioactivity, biocompatibility and mechanical behavior of strontium substituted bioactive glasses

    Energy Technology Data Exchange (ETDEWEB)

    Arepalli, Sampath Kumar, E-mail: askumar.rs.cer11@iitbhu.ac.in [Department of Ceramic Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005 (India); Tripathi, Himanshu [Department of Ceramic Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005 (India); Hira, Sumit Kumar; Manna, Partha Pratim [Immunobiology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005 (India); Pyare, Ram; Singh, S.P. [Department of Ceramic Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005 (India)

    2016-12-01

    Strontium contained biomaterials have been reported as a potential bioactive material for bone regeneration, as it reduces bone resorption and stimulates bone formation. In the present investigation, the bioactive glasses were designed to partially substitute SrO for SiO{sub 2} in Na{sub 2}O–CaO–SrO–P{sub 2}O{sub 5}–SiO{sub 2} system. This work demonstrates that the substitution of SrO for SiO{sub 2} has got significant benefit than substitution for CaO in the bioactive glass. Bioactivity was assessed by the immersion of the samples in simulated body fluid for different intervals. The formation of hydroxy carbonate apatite layer was identified by X-ray diffractometry, scanning electron microscopy (SEM) and energy dispersive spectroscopy. The elastic modulus of the bioactive glasses was measured and found to increase with increasing SrO for SiO{sub 2}. The blood compatibility of the samples was evaluated. In vitro cell culture studies of the samples were performed using human osteosarcoma U2-OS cell lines and found a significant improvement in cell viability and proliferation. The investigation showed enhancement in bioactivity, mechanical and biological properties of the strontia substituted for silica in glasses. Thus, these bioactive glasses would be highly potential for bone regeneration. - Highlights: • The substitution of SrO was done for SiO{sub 2} in Na{sub 2}O–CaO–SrO–P{sub 2}O{sub 5}–SiO{sub 2} bioactive glass. • Network connectivity significantly influenced on bioactivity and biocompatibility. • In vitro SBF studies showed enhanced HCA crystallinity on the glass surface. • The cell culture studies exhibited better cell compatibility and significant growth. • Density and elastic moduli increased with increasing concentration of strontia.

  5. Enhanced bioactivity, biocompatibility and mechanical behavior of strontium substituted bioactive glasses

    International Nuclear Information System (INIS)

    Arepalli, Sampath Kumar; Tripathi, Himanshu; Hira, Sumit Kumar; Manna, Partha Pratim; Pyare, Ram; Singh, S.P.

    2016-01-01

    Strontium contained biomaterials have been reported as a potential bioactive material for bone regeneration, as it reduces bone resorption and stimulates bone formation. In the present investigation, the bioactive glasses were designed to partially substitute SrO for SiO 2 in Na 2 O–CaO–SrO–P 2 O 5 –SiO 2 system. This work demonstrates that the substitution of SrO for SiO 2 has got significant benefit than substitution for CaO in the bioactive glass. Bioactivity was assessed by the immersion of the samples in simulated body fluid for different intervals. The formation of hydroxy carbonate apatite layer was identified by X-ray diffractometry, scanning electron microscopy (SEM) and energy dispersive spectroscopy. The elastic modulus of the bioactive glasses was measured and found to increase with increasing SrO for SiO 2 . The blood compatibility of the samples was evaluated. In vitro cell culture studies of the samples were performed using human osteosarcoma U2-OS cell lines and found a significant improvement in cell viability and proliferation. The investigation showed enhancement in bioactivity, mechanical and biological properties of the strontia substituted for silica in glasses. Thus, these bioactive glasses would be highly potential for bone regeneration. - Highlights: • The substitution of SrO was done for SiO 2 in Na 2 O–CaO–SrO–P 2 O 5 –SiO 2 bioactive glass. • Network connectivity significantly influenced on bioactivity and biocompatibility. • In vitro SBF studies showed enhanced HCA crystallinity on the glass surface. • The cell culture studies exhibited better cell compatibility and significant growth. • Density and elastic moduli increased with increasing concentration of strontia.

  6. Structure, bioactivity, and synthesis of methylated flavonoids.

    Science.gov (United States)

    Wen, Lingrong; Jiang, Yueming; Yang, Jiali; Zhao, Yupeng; Tian, Miaomiao; Yang, Bao

    2017-06-01

    Methylated flavonoids are an important type of natural flavonoid derivative with potentially multiple health benefits; among other things, they have improved bioavailability compared with flavonoid precursors. Flavonoids have been documented to have broad bioactivities, such as anticancer, immunomodulation, and antioxidant activities, that can be elevated, to a certain extent, by methylation. Understanding the structure, bioactivity, and bioavailability of methylated flavonoids, therefore, is an interesting topic with broad potential applications. Though methylated flavonoids are widely present in plants, their levels are usually low. Because developing efficient techniques to produce these chemicals would likely be beneficial, we provide an overview of their chemical and biological synthesis. © 2017 New York Academy of Sciences.

  7. The effect of growth hormone on bioactive IGF in overweight/obese women.

    Science.gov (United States)

    Dichtel, Laura E; Bjerre, Mette; Schorr, Melanie; Bredella, Miriam A; Gerweck, Anu V; Russell, Brian M; Frystyk, Jan; Miller, Karen K

    2018-03-10

    Overweight/obesity is characterized by decreased growth hormone (GH) secretion whereas circulating IGF-I levels are less severely reduced. Yet, the activity of the circulating IGF-system appears to be normal in overweight/obese subjects, as estimated by the ability of serum to activate the IGF-I receptor in vitro (bioactive IGF). We hypothesized that preservation of bioactive IGF in overweight/obese women is regulated by an insulin-mediated suppression of IGF-binding protein-1 (IGFBP-1) and IGFBP-2, and by suppression of IGFBP-3, mediated by low GH. We additionally hypothesized that increases in bioactive IGF would drive changes in body composition with low-dose GH administration. Cross-sectional analysis and 3-month interim analysis of a 6-month randomized, placebo-controlled study of GH administration in 50 overweight/obese women without diabetes mellitus. Bioactive IGF (kinase receptor activation assay) and body composition (DXA) were measured. Prior to treatment, IGFBP-3 (r = -0.33, p = 0.02), but neither IGFBP-1 nor IGFBP-2, associated inversely with bioactive IGF. In multivariate analysis, lower IGFBP-3 correlated with lower peak stimulated GH (r = 0.45, p = 0.05) and higher insulin sensitivity (r = -0.74, p = 0.003). GH administration resulted in an increase in mean serum IGF-I concentrations (144 ± 56 to 269 ± 66 μg/L, p IGF (1.29 ± 0.39 to 2.60 ± 1.12 μg/L, p IGF, but not total IGF-I concentration, predicted an increase in lean mass (r = 0.31, p = 0.03) and decrease in total adipose tissue/BMI (r = -0.43, p = 0.003). Our data suggest that in overweight/obesity, insulin sensitivity and GH have opposing effects on IGF bioactivity through effects on IGFBP-3. Furthermore, increases in bioactive IGF, rather than IGF-I concentration, predicted GH administration-related body composition changes. NCT00131378. Copyright © 2018. Published by Elsevier Ltd.

  8. Increased lipid droplet accumulation associated with a peripheral sensory neuropathy.

    Science.gov (United States)

    Marshall, Lee L; Stimpson, Scott E; Hyland, Ryan; Coorssen, Jens R; Myers, Simon J

    2014-04-01

    Hereditary sensory neuropathy type 1 (HSN-1) is an autosomal dominant neurodegenerative disease caused by missense mutations in the SPTLC1 gene. The SPTLC1 protein is part of the SPT enzyme which is a ubiquitously expressed, critical and thus highly regulated endoplasmic reticulum bound membrane enzyme that maintains sphingolipid concentrations and thus contributes to lipid metabolism, signalling, and membrane structural functions. Lipid droplets are dynamic organelles containing sphingolipids and membrane bound proteins surrounding a core of neutral lipids, and thus mediate the intracellular transport of these specific molecules. Current literature suggests that there are increased numbers of lipid droplets and alterations of lipid metabolism in a variety of other autosomal dominant neurodegenerative diseases, including Alzheimer's and Parkinson's disease. This study establishes for the first time, a significant increase in the presence of lipid droplets in HSN-1 patient-derived lymphoblasts, indicating a potential connection between lipid droplets and the pathomechanism of HSN-1. However, the expression of adipophilin (ADFP), which has been implicated in the regulation of lipid metabolism, was not altered in lipid droplets from the HSN-1 patient-derived lymphoblasts. This appears to be the first report of increased lipid body accumulation in a peripheral neuropathy, suggesting a fundamental molecular linkage between a number of neurodegenerative diseases.

  9. Surface coated polyurethane with improved bioactivity and cytocompatability

    CSIR Research Space (South Africa)

    Chetty, AS

    2006-02-01

    Full Text Available Polyurethane (PU) may be suitable for various implant applications; however, it lacks bioactivity. Bioactivity allows for direct tissue attachment at the bio- interface, enabling implant fixation while preventing fibrous encapsulation. To impart...

  10. Bioactive glass-based scaffolds for bone tissue engineering

    NARCIS (Netherlands)

    Will, J.; Gerhardt, L.C.; Boccaccini, A.R.

    2012-01-01

    Originally developed to fill and restore bone defects, bioactive glasses are currently also being intensively investigated for bone tissue engineering applications. In this chapter, we review and discuss current knowledge on porous bone tissue engineering scaffolds made from bioactive silicate

  11. Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle.

    Science.gov (United States)

    Trinchese, Giovanna; Cavaliere, Gina; De Filippo, Chiara; Aceto, Serena; Prisco, Marina; Chun, Jong Tai; Penna, Eduardo; Negri, Rossella; Muredda, Laura; Demurtas, Andrea; Banni, Sebastiano; Berni-Canani, Roberto; Mattace Raso, Giuseppina; Calignano, Antonio; Meli, Rosaria; Greco, Luigi; Crispino, Marianna; Mollica, Maria P

    2018-01-01

    Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention. Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue. Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA), a key regulator of lipid metabolism and inflammation. Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of mitochondrial function

  12. Testing the Role of Microbial Ecology, Redox-Mediated Deep Water Production and Hypersalinity on TEX86: Lipids and 16s Sequences from Archaea and Bacteria in the Water Column and Sediments of Orca Basin

    Science.gov (United States)

    Warren, C.; Romero, I.; Ellis, G.; Goddard, E.; Krishnan, S.; Nigro, L. M.; Super, J. R.; Zhang, Y.; Zhuang, G.; Hollander, D. J.; Pagani, M.

    2014-12-01

    Mesophilic marine archaea and bacteria are known to substantially contribute to the oceanic microbial biomass and play critical roles in global carbon, nitrogen and nutrient cycles. The Orca Basin, a 2400 meter deep bathymetric depression on the continental slope of the north-central Gulf of Mexico, is an ideal environment to examine how redox-dependent biochemical processes control the input and cycling of bacterial and archaea-derived lipid compounds from formation in near-surface water, through secondary recycling processes operating at the redox-transition in the water column, to sedimentary diagenetic processes operating in oxic to anoxic zones within the basin. The lowermost 180 meters of the Orca Basin is characterized by an anoxic, hypersaline brine that is separated from the overlying oxic seawater by a well-defined redox sequence associated with a systematic increasing in salinity from 35 - 250‰. While surface water conditions are viewed as normal marine with a seasonally productive water column, the sub-oxic to anoxic transition zones within the deep-water column and the sediment spans over 200 m allowing the unique opportunity for discrete sampling of resident organisms and lipids. Here we present 16s rRNA sequence data of Bacteria and Archaea collected parallel to GDGT lipid profiles and in situ environmental measurements from the sediment and overlying water column in the intermediate zone of the basin, where movements of chemical transition zones are preserved. We evaluated GDGTs and corresponding taxa across the surface water, chlorophyll maximum, thermocline, and the deep redox boundary, including oxygenation, denitrification, manganese, iron and sulfate reduction zones, to determine if GDGTs are being produced under these conditions and how surface-derived GDGT lipids and the TEX86 signal may be altered. The results have implications for the application of the TEX86 paleotemperature proxy.

  13. Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Giovanna Trinchese

    2018-01-01

    Full Text Available Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM and donkey milk (DM are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM, DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention.Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue.Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA, a key regulator of lipid metabolism and inflammation.Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of

  14. Dimethyl carbonate-mediated lipid extraction and lipase-catalyzed in situ transesterification for simultaneous preparation of fatty acid methyl esters and glycerol carbonate from Chlorella sp. KR-1 biomass.

    Science.gov (United States)

    Jo, Yoon Ju; Lee, Ok Kyung; Lee, Eun Yeol

    2014-04-01

    Fatty acid methyl esters (FAMEs) and glycerol carbonate were simultaneously prepared from Chlorella sp. KR-1 containing 40.9% (w/w) lipid using a reactive extraction method with dimethyl carbonate (DMC). DMC was used as lipid extraction agent, acyl acceptor for transesterification of the extracted triglycerides, substrate for glycerol carbonate synthesis from glycerol, and reaction medium for the solvent-free reaction system. For 1g of biomass, 367.31 mg of FAMEs and 16.73 mg of glycerol carbonate were obtained under the optimized conditions: DMC to biomass ratio of 10:1 (v/w), water content of 0.5% (v/v), and Novozyme 435 to biomass ratio of 20% (w/w) at 70°C for 24h. The amount of residual glycerol was only in the range of 1-2.5mg. Compared to conventional method, the cost of FAME production with the proposed technique could be reduced by combining lipid extraction with transesterification and omitting the extraction solvent recovery process. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Autophagy, lipophagy and lysosomal lipid storage disorders.

    Science.gov (United States)

    Ward, Carl; Martinez-Lopez, Nuria; Otten, Elsje G; Carroll, Bernadette; Maetzel, Dorothea; Singh, Rajat; Sarkar, Sovan; Korolchuk, Viktor I

    2016-04-01

    Autophagy is a catabolic process with an essential function in the maintenance of cellular and tissue homeostasis. It is primarily recognised for its role in the degradation of dysfunctional proteins and unwanted organelles, however in recent years the range of autophagy substrates has also been extended to lipids. Degradation of lipids via autophagy is termed lipophagy. The ability of autophagy to contribute to the maintenance of lipo-homeostasis becomes particularly relevant in the context of genetic lysosomal storage disorders where perturbations of autophagic flux have been suggested to contribute to the disease aetiology. Here we review recent discoveries of the molecular mechanisms mediating lipid turnover by the autophagy pathways. We further focus on the relevance of autophagy, and specifically lipophagy, to the disease mechanisms. Moreover, autophagy is also discussed as a potential therapeutic target in several key lysosomal storage disorders. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules

    Directory of Open Access Journals (Sweden)

    Dorothy Moseti

    2016-01-01

    Full Text Available Adipogenesis is the process by which precursor stem cells differentiate into lipid laden adipocytes. Adipogenesis is regulated by a complex and highly orchestrated gene expression program. In mammalian cells, the peroxisome proliferator-activated receptor γ (PPARγ, and the CCAAT/enhancer binding proteins (C/EBPs such as C/EBPα, β and δ are considered the key early regulators of adipogenesis, while fatty acid binding protein 4 (FABP4, adiponectin, and fatty acid synthase (FAS are responsible for the formation of mature adipocytes. Excess accumulation of lipids in the adipose tissue leads to obesity, which is associated with cardiovascular diseases, type II diabetes and other pathologies. Thus, investigating adipose tissue development and the underlying molecular mechanisms is vital to develop therapeutic agents capable of curbing the increasing incidence of obesity and related pathologies. In this review, we address the process of adipogenic differentiation, key transcription factors and proteins involved, adipogenic regulators and potential anti-adipogenic bioactive molecules.

  17. Accelerated bone ingrowth by local delivery of Zinc from bioactive ...

    African Journals Online (AJOL)

    2015-10-19

    Oct 19, 2015 ... Aims: This study aims to evaluate in vivo the performance therapy of zinc-doped bioactive glass (BG-Zn) and ... Keywords: zinc metallic ion; bioactive glass; osteoporosis; trabecular bone architecture; mechanical property; oxidative stress ..... Ducheyne P, Qiu Q. Bioactive ceramics: the effect of surface.

  18. Investigation of bioactivity and cell effects of nano-porous sol–gel derived bioactive glass film

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Zhijun, E-mail: mokuu@zju.edu.cn [State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou, 510640 (China); Ji, Huijiao [College of Life Science, Zhejiang University, Hangzhou, 310028 (China); Hu, Xiaomeng [School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640 (China); Teng, Yu [State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou, 510640 (China); Zhao, Guiyun; Mo, Lijuan; Zhao, Xiaoli [College of Life Science, Zhejiang University, Hangzhou, 310028 (China); Chen, Weibo [School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640 (China); Qiu, Jianrong, E-mail: qjr@scut.edu.cn [State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou, 510640 (China); Zhang, Ming, E-mail: zhangming201201@126.com [College of Life Science, Zhejiang University, Hangzhou, 310028 (China)

    2013-11-01

    In orthopedic surgery, bioactive glass film coating is extensively studied to improve the synthetic performance of orthopedic implants. A lot of investigations have confirmed that nano-porous structure in bioactive glasses can remarkably improve their bioactivity. Nevertheless, researches on preparation of nano-porous bioactive glasses in the form of film coating and their cell response activities are scarce. Herein, we report the preparation of nano-porous bioactive glass film on commercial glass slide based on a sol–gel technique, together with the evaluation of its in vitro bioactivity through immersion in simulated body fluid and monitoring the precipitation of apatite-like layer. Cell responses of the samples, including attachment, proliferation and osteogenic differentiation, were also investigated using BMSCS (bone marrow derived mesenchymal stem cells) as a model. The results presented here provide some basic information on structural influence of bioactive glass film on the improvement of bioactivity and cellular effects.

  19. Investigation of bioactivity and cell effects of nano-porous sol-gel derived bioactive glass film

    Science.gov (United States)

    Ma, Zhijun; Ji, Huijiao; Hu, Xiaomeng; Teng, Yu; Zhao, Guiyun; Mo, Lijuan; Zhao, Xiaoli; Chen, Weibo; Qiu, Jianrong; Zhang, Ming

    2013-11-01

    In orthopedic surgery, bioactive glass film coating is extensively studied to improve the synthetic performance of orthopedic implants. A lot of investigations have confirmed that nano-porous structure in bioactive glasses can remarkably improve their bioactivity. Nevertheless, researches on preparation of nano-porous bioactive glasses in the form of film coating and their cell response activities are scarce. Herein, we report the preparation of nano-porous bioactive glass film on commercial glass slide based on a sol-gel technique, together with the evaluation of its in vitro bioactivity through immersion in simulated body fluid and monitoring the precipitation of apatite-like layer. Cell responses of the samples, including attachment, proliferation and osteogenic differentiation, were also investigated using BMSCS (bone marrow derived mesenchymal stem cells) as a model. The results presented here provide some basic information on structural influence of bioactive glass film on the improvement of bioactivity and cellular effects.

  20. Bioactive compounds in potatoes: Accumulation under drought stress conditions

    Directory of Open Access Journals (Sweden)

    Christina B. Wegener

    2015-03-01

    Full Text Available Background: Potato (Solanum tuberosum is a valuable source of bioactive compounds. Besides starch, crude fibre, amino acids (AAS, vitamins and minerals, the tubers contain diverse phenolic compounds. These phenolics and AAS confer anti-oxidant protection against reactiveoxygen species, tissue damage, and diseases like atherosclerosis, renal failure, diabetes mellitus,and cancer. Climate change and drought stress may become a major risk for crop production worldwide, resulting in reduced access for those who depend on the nutritional value of this staple crop. Objective: The aim of this study is to determine the effect of drought stress on water, lipid soluble antioxidants, anthocyanins (Ac, soluble phenols, proteins, free AAS, peroxidase (POD and lipid acyl hydrolase activity (LAH in tuber tissue. Methods: The study was carried out on three potato genotypes comprising one yellow-fleshed cultivar and two purple breeding clones. The plants were grown in pots (from April to September in a glasshouse with sufficient water supply and under drought stress conditions. After harvest, the tubers of both variants were analysed for antioxidants measured as ascorbic acid (ACE and Trolox equivalent (TXE using a photo-chemiluminescent method. Amounts of anthocyanins (Ac, soluble phenols, proteins, as well as POD and LAH activities were analysed using a UV photometer. Finally, free AAS were measured by HPLC. Results: The results revealed that drought stress significantly reduces tuber yield, but has no significant effect on antioxidants, Ac, soluble phenols and POD. Drought stress significantly increased the levels of soluble protein (P < 0.0001 and LAH (P < 0.001. Also, total amounts of free AAS were higher in the drought stressed tubers (+34.2%, on average than in the tubers grown with a sufficient water supply. Above all, proline was elevated due to drought stress.

  1. Encapsulation for preservation of functionality and targeted delivery of bioactive food components

    NARCIS (Netherlands)

    de Vos, Paul; Faas, Marijke M.; Spasojevic, Milica; Sikkema, Jan

    There has been a tremendous increase in the number of food products containing bioactive components with a health promoting or disease preventing effect. Bioactive food components can be divided into bioactive molecules and bioactive living cells (probiotics). Both bioactive molecules and bioactive

  2. Polyene-lipids: a new tool to image lipids

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Ejsing, Christer S.; Ekroos, Kim

    2005-01-01

    conjugated double bonds as a new type of lipid tag. Polyene-lipids exhibit a unique structural similarity to natural lipids, which results in minimal effects on the lipid properties. Analyzing membrane phase partitioning, an important biophysical and biological property of lipids, we demonstrated......Microscopy of lipids in living cells is currently hampered by a lack of adequate fluorescent tags. The most frequently used tags, NBD and BODIPY, strongly influence the properties of lipids, yielding analogs with quite different characteristics. Here, we introduce polyene-lipids containing five...... the superiority of polyene-lipids to both NBD- and BODIPY-tagged lipids. Cells readily take up various polyene-lipid precursors and generate the expected end products with no apparent disturbance by the tag. Applying two-photon excitation microscopy, we imaged the distribution of polyene-lipids in living...

  3. Microstructures, hardness and bioactivity of hydroxyapatite coatings

    CSIR Research Space (South Africa)

    Tlotleng, Monnamme

    2014-10-01

    Full Text Available Hydroxyapatite (HAP) coatings on bioinert metals such as Ti–6Al–4V are necessary for biomedical applications. Together, HAP and Ti–6Al–4V are biocompatible and bioactive. The challenges of depositing HAP on Ti–6Al–4V with traditional thermal...

  4. Marine bioactives and potential application in sports.

    Science.gov (United States)

    Gammone, Maria Alessandra; Gemello, Eugenio; Riccioni, Graziano; D'Orazio, Nicolantonio

    2014-04-30

    An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

  5. Bioactive Compounds And Encapsulation Of Yanang ( Tiliacora ...

    African Journals Online (AJOL)

    Furthermore, this paper reports the design of the experimental method for optimization of Yanang encapsulation using three independent variables: the ratio of core material (Yanang), to wall material (gum Arabic), gum Arabic concentration and inlet temperature of spray drying on bioactive compounds stability. The stability ...

  6. Natural bioactive compounds: antibiotics | Dezfully | Journal of ...

    African Journals Online (AJOL)

    Antibiotics are powerful therapeutic agents that are produced by diverse living organisms. Over the last several decades, natural bioactive products particularly antibiotics have continued to play a significant role in drug discovery and has expanded the process for developing drugs with high degree of therapeutic index and ...

  7. Extraction, Isolation And Characterization Of Bioactive Compounds ...

    African Journals Online (AJOL)

    Natural products from medicinal plants, either as pure compounds or as standardized extracts, provide unlimited opportunities for new drug leads because of the ... The analysis of bioactive compounds present in the plant extracts involving the applications of common phytochemical screening assays, chromatographic ...

  8. Mechanical properties of bioactive glass putty formulations

    NARCIS (Netherlands)

    van Gestel, N.A.P.; Geurts, J.A.P.; Hulsen, D.J.W.; Hofmann, S.; Ito, K.; van Rietbergen, B.; Arts, J.J.C.

    2016-01-01

    Introduction: Bioactive glass (BAG) has been studied widely and seems to be a very promising biomaterial in regeneration of large bone defects and osteomyelitis treatment, because of its bone bonding and antibacterial properties[1]-[5]. Its high stiffness could potentially also enable mechanical

  9. Bioactive compounds in whole grain wheat

    NARCIS (Netherlands)

    Mateo Anson, N.

    2010-01-01

    Bread can be healthier! Consuming whole-grain foods can prevent cardiovascular diseases, type-2 diabetes and metabolic syndrome. This is due to bioactive compounds in whole grain, such as antioxidants and anti-inflammatory compounds. We found that the different fractions of a wheat grain vary much

  10. Legume bioactive compounds: influence of rhizobial inoculation

    Directory of Open Access Journals (Sweden)

    Luis R. Silva

    2017-04-01

    Full Text Available Legumes consumption has been recognized as beneficial for human health, due to their content in proteins, fiber, minerals and vitamins, and their cultivation as beneficial for sustainable agriculture due to their ability to fix atmospheric nitrogen in symbiosis with soil bacteria known as rhizobia. The inoculation with these baceria induces metabolic changes in the plant, from which the more studied to date are the increases in the nitrogen and protein contents, and has been exploited in agriculture to improve the crop yield of several legumes. Nevertheless, legumes also contain several bioactive compounds such as polysaccharides, bioactive peptides, isoflavones and other phenolic compounds, carotenoids, tocopherols and fatty acids, which makes them functional foods included into the nutraceutical products. Therefore, the study of the effect of the rhizobial inoculation in the legume bioactive compounds content is gaining interest in the last decade. Several works reported that the inoculation of different genera and species of rhizobia in several grain legumes, such as soybean, cowpea, chickpea, faba bean or peanut, produced increases in the antioxidant potential and in the content of some bioactive compounds, such as phenolics, flavonoids, organic acids, proteins and fatty acids. Therefore, the rhizobial inoculation is a good tool to enhance the yield and quality of legumes and further studies on this field will allow us to have plant probiotic bacteria that promote the plant growth of legumes improving their functionality.

  11. The evolution of lipids

    Science.gov (United States)

    Itoh, Y. H.; Sugai, A.; Uda, I.; Itoh, T.

    2001-01-01

    Living organisms on the Earth which are divided into three major domains - Archaea, Bacteria, and Eucarya, probably came from a common ancestral cell. Because there are many thermophilic microorganisms near the root of the universal phylogenetic tree, the common ancestral cell should be considered to be a thermophilic microorganism. The existence of a cell is necessary for the living organisms; the cell membrane is the essential structural component of a cell, so its amphiphilic property is vital for the molecule of lipids for cell membranes. Tetraether type glycerophospholipids with C 40 isoprenoid chains are major membrane lipids widely distributed in archaeal cells. Cyclization number of C 40 isoprenoid chains in thermophilic archaea influences the fluidity of lipids whereas the number of carbons and degree of unsaturation in fatty acids do so in bacteria and eucarya. In addition to the cyclization of the tetraether lipids, covalent bonding of two C 40 isoprenoid chains was found in hyperthermophiles. These characteristic structures of the lipids seem to contribute to their fundamental physiological roles in hyperthermophiles. Stereochemical differences between G-1-P archaeal lipids and G-3-P bacterial and eucaryal lipids might have occured by the function of some proteins long after the first cell was developed by the reactions of small organic molecules. We propose that the structure of lipids of the common ancestral cell may have been similar to those of hyperthermophilic archaea.

  12. Lysosomal lipid storage diseases.

    Science.gov (United States)

    Schulze, Heike; Sandhoff, Konrad

    2011-06-01

    Lysosomal lipid storage diseases, or lipidoses, are inherited metabolic disorders in which typically lipids accumulate in cells and tissues. Complex lipids, such as glycosphingolipids, are constitutively degraded within the endolysosomal system by soluble hydrolytic enzymes with the help of lipid binding proteins in a sequential manner. Because of a functionally impaired hydrolase or auxiliary protein, their lipid substrates cannot be degraded, accumulate in the lysosome, and slowly spread to other intracellular membranes. In Niemann-Pick type C disease, cholesterol transport is impaired and unesterified cholesterol accumulates in the late endosome. In most lysosomal lipid storage diseases, the accumulation of one or few lipids leads to the coprecipitation of other hydrophobic substances in the endolysosomal system, such as lipids and proteins, causing a "traffic jam." This can impair lysosomal function, such as delivery of nutrients through the endolysosomal system, leading to a state of cellular starvation. Therapeutic approaches are currently restricted to mild forms of diseases with significant residual catabolic activities and without brain involvement.

  13. Lipid bilayers and interfaces

    NARCIS (Netherlands)

    Kik, R.A.

    2007-01-01

    In biological systems lipid bilayers are subject to many different interactions with other entities. These can range from proteins that are attached to the hydrophilic region of the bilayer or transmembrane proteins that interact with the hydrophobic region of the lipid bilayer. Interaction between

  14. Preparation and bioactive properties of nano bioactive glass and segmented polyurethane composites.

    Science.gov (United States)

    Aguilar-Pérez, Fernando J; Vargas-Coronado, Rossana F; Cervantes-Uc, Jose M; Cauich-Rodríguez, Juan V; Covarrubias, Cristian; Pedram-Yazdani, Merhdad

    2016-04-01

    Composites of glutamine-based segmented polyurethanes with 5 to 25 wt.% bioactive glass nanoparticles were prepared, characterized, and their mineralization potential was evaluated in simulated body fluid. Biocompatibility with dental pulp stem cells was assessed by MTS to an extended range of compositions (1 to 25 wt.% of bioactive glass nanoparticles). Physicochemical characterization showed that composites retained many of the matrix properties, i.e. those corresponding to semicrystalline elastomeric polymers as they exhibited a glass transition temperature (Tg) between -41 and -36℃ and a melting temperature (Tm) between 46 and 49℃ in agreement with X-ray reflections at 23.6° and 21.3°. However, with bioactive glass nanoparticles addition, tensile strength and strain were reduced from 22.2 to 12.2 MPa and 667.2 to 457.8%, respectively with 25 wt.% of bioactive glass nanoparticles. Although Fourier transform infrared spectroscopy did not show evidence of mineralization after conditioning of these composites in simulated body fluid, X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray microanalysis showed the formation of an apatite layer on the surface which increased with higher bioactive glass concentrations and longer conditioning time. Dental pulp stem cells proliferation at day 5 was improved in bioactive glass nanoparticles composites containing lower amounts of the filler (1-2.5 wt.%) but it was compromised at day 9 in composites containing high contents of nBG (5, 15, 25 wt.%). However, Runx2 gene expression was particularly upregulated for the dental pulp stem cells cultured with composites loaded with 15 and 25 wt.% of bioactive glass nanoparticles. In conclusion, low content bioactive glass nanoparticles and segmented polyurethanes composites deserve further investigation for applications such as guided bone regeneration membranes, where osteoconductivity is desirable but not a demanding mechanical performance. © The

  15. Thermal analysis and in vitro bioactivity of bioactive glass-alumina composites

    Energy Technology Data Exchange (ETDEWEB)

    Chatzistavrou, Xanthippi, E-mail: x.chatzistavrou@imperial.ac.uk [Solid State Physics Section, Physics Department, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Kantiranis, Nikolaos, E-mail: kantira@geo.auth.gr [School of Geology, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Kontonasaki, Eleana, E-mail: kont@dent.auth.gr [School of Dentistry, Department of Fixed Prosthesis and Implant Prosthodontics, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Chrissafis, Konstantinos, E-mail: hrisafis@physics.auth.gr [Solid State Physics Section, Physics Department, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Papadopoulou, Labrini, E-mail: lambrini@geo.auth.gr [School of Geology, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Koidis, Petros, E-mail: pkoidis@dent.auth.gr [School of Dentistry, Department of Fixed Prosthesis and Implant Prosthodontics, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Boccaccini, Aldo R., E-mail: a.boccaccini@imperial.ac.uk [Department of Materials, Faculty of Engineering, Imperial College, SW7 2AZ London (United Kingdom); Paraskevopoulos, Konstantinos M., E-mail: kpar@auth.gr [Solid State Physics Section, Physics Department, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece)

    2011-01-15

    Bioactive glass-alumina composite (BA) pellets were fabricated in the range 95/5-60/40 wt.% respectively and were heat-treated under a specific thermal treatment up to 950 {sup o}C. Control (unheated) and heat-treated pellets were immersed in Simulated Body Fluid (SBF) for bioactivity testing. All pellets before and after immersion in SBF were studied by Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM-EDS) and X-ray Diffraction (XRD) analysis. All composite pellets presented bioactive response. On the surface of the heat-treated pellets the development of a rich biological hydroxyapatite (HAp) layer was delayed for one day, compared to the respective control pellets. Independent of the proportion of the two components, all composites of each group (control and heat-treated) presented the same bioactive response as a function of immersion time in SBF. It was found that by the applied methodology, Al{sub 2}O{sub 3} can be successfully applied in bioactive glass composites without obstructing their bioactive response. - Research Highlights: {yields} Isostatically pressed glass-alumina composites presented apatite-forming ability. {yields} The interaction with SBF resulted in an aluminium phosphate phase formation. {yields} The formation of an aluminium phosphate phase enhanced the in vitro apatite growth.

  16. Hibiscus sabdariffa L. as a source of nutrients, bioactive compounds and colouring agents.

    Science.gov (United States)

    Jabeur, Inès; Pereira, Eliana; Barros, Lillian; Calhelha, Ricardo C; Soković, Marina; Oliveira, M Beatriz P P; Ferreira, Isabel C F R

    2017-10-01

    The nutritional and bioactive composition of plants have aroused much interest not only among scientists, but also in people's daily lives. Apart from the health benefits, plants are a source of pigments that can be used as natural food colorants. In this work, the nutritional composition of Hibiscus sabdariffa L. was analysed, as well as its bioactive compounds and natural pigments. Glucose (sugar), malic acid (organic acid), α-tocopherol (tocopherol) and linoleic acid (fatty acid) were the major constituents in the corresponding classes. 5-(Hydroxymethyl) furfural was the most abundant non-anthocyanin compound, while delphinidin-3-O-sambubioside was the major anthocyanin both in its hydroethanolic extract and infusion. H. sabdariffa extracts showed antioxidant and antimicrobial activities, highlighting that the hydroethanol extract presents not only lipid peroxidation inhibition capacity, but also bactericidal/fungicidal inhibition ability for all the bacteria and fungi tested. Furthermore, both extracts revealed the absence of toxicity using porcine primary liver cells. The studied plant species was thus not only interesting for nutritional purposes but also for bioactive and colouring applications in food, cosmetic and pharmaceutical industries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Nutrients, phytochemicals and bioactivity of wild Roman chamomile: a comparison between the herb and its preparations.

    Science.gov (United States)

    Guimarães, Rafaela; Barros, Lillian; Dueñas, Montserrat; Calhelha, Ricardo C; Carvalho, Ana Maria; Santos-Buelga, Celestino; Queiroz, Maria João R P; Ferreira, Isabel C F R

    2013-01-15

    Roman chamomile, Chamaemelum nobile L. (Asteraceae), has been used for medicinal applications, mainly through oral dosage forms (decoctions and infusions). Herein, the nutritional characterisation of C. nobile was performed, and herbal material and its decoction and infusion were submitted to an analysis of phytochemicals and bioactivity evaluation. The antioxidant activity was determined by free radicals scavenging activity, reducing power and inhibition of lipid peroxidation, the antitumour potential was tested in human tumour cell lines (breast, lung, colon, cervical and hepatocellular carcinomas), and the hepatotoxicity was evaluated using a porcine liver primary cell culture. C. nobile proved to be an equilibrated valuable herb rich in carbohydrates and proteins, and poor in fat, providing tocopherols, carotenoids and essential fatty acids (C18:2n6 and C18:3n3). Moreover, the herb and its infusion are a source of phenolic compounds (flavonoids such as flavonols and flavones, phenolic acids and derivatives) and organic acids (oxalic, quinic, malic, citric and fumaric acids) that showed antioxidant and antitumour activities, without hepatotoxicity. The most abundant compounds in the plant extract and infusion were 5-O-caffeoylquinic acid and an apigenin derivative. These, as well as other bioactive compounds, are affected in C. nobile decoction, leading to a lower antioxidant potential and absence of antitumour potential. The plant bioactivity could be explored in the medicine, food, and cosmetic industries. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Hydration dynamics of a lipid membrane: Hydrogen bond networks and lipid-lipid associations

    Science.gov (United States)

    Srivastava, Abhinav; Debnath, Ananya

    2018-03-01

    reveal that the slow relaxation rates of interfacial waters in the vicinity of lipids are originated from the chemical confinement of concerted hydrogen bond networks. The analysis suggests that the networks in the hydration layer of membranes dynamically facilitate the water mediated lipid-lipid associations which can provide insights on the thermodynamic stability of soft interfaces relevant to biological systems in the future.

  19. Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

    Science.gov (United States)

    Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

    2009-11-01

    Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

  20. Antioxidant activities and skin hydration effects of rice bran bioactive compounds entrapped in niosomes.

    Science.gov (United States)

    Manosroi, Aranya; Chutoprapat, Romchat; Sato, Yuji; Miyamoto, Kukizo; Hsueh, Kesyin; Abe, Masahiko; Manosroi, Worapaka; Manosroi, Jiradej

    2011-03-01

    Bioactive compounds [ferulic acid (F), gamma-oryzanol (O) and phytic acid (P)] in rice bran have been widely used as antioxidants in skin care products. However, one of the major problems of antioxidants is the deterioration of their activities during long exposure to air and light. Niosomes have been used to entrap many degradable active agents not only for stability improvement, but also for increasing skin hydration. The objective of this study was to determine antioxidant activities [by in vitro ORAC (oxygen radical absorbance capacity) and ex vivo lipid peroxidation inhibition assay] and in vivo human skin hydration effects of gel and cream containing the rice bran extracts entrapped in niosomes. Gel and cream containing the rice bran extracts entrapped in niosomes showed higher antioxidant activity (ORAC value) at 20-28 micromol of Trolox equivalents (TE) per gram of the sample than the placebo gel and cream which gave 16-18 micromolTE/g. Human sebum treated with these formulations showed more lipid peroxidation inhibition activity than with no treatment of about 1.5 times. The three different independent techniques including corneometer, vapometer and confocal Raman microspectroscopy (CRM) indicated the same trend in human skin hydration enhancement of the gel or cream formulations containing the rice bran extracts entrapped in niosomes of about 20, 3 and 30%, respectively. This study has demonstrated the antioxidant activities and skin hydration enhancement of the rice bran bioactive compounds when entrapped in niosomes and incorporated in cream formulations.

  1. Plasma lipoproteins as mediators of the oxidative stress induced by UV light in human skin: a review of biochemical and biophysical studies on mechanisms of apolipoprotein alteration, lipid peroxidation, and associated skin cell responses.

    Science.gov (United States)

    Filipe, Paulo; Morlière, Patrice; Silva, João N; Mazière, Jean-Claude; Patterson, Larry K; Freitas, João P; Santus, R

    2013-01-01

    There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL) and low-density lipoprotein (LDL) as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces (•)Trp and (•)O2 (-) radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO(•)) by α -tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α -tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α -tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α -tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

  2. Plasma Lipoproteins as Mediators of the Oxidative Stress Induced by UV Light in Human Skin: A Review of Biochemical and Biophysical Studies on Mechanisms of Apolipoprotein Alteration, Lipid Peroxidation, and Associated Skin Cell Responses

    Directory of Open Access Journals (Sweden)

    Paulo Filipe

    2013-01-01

    Full Text Available There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL and low-density lipoprotein (LDL as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces •Trp and O2•- radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO• by α-tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α-tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α-tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α-tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

  3. Synthesis of Lipidated Proteins.

    Science.gov (United States)

    Mejuch, Tom; Waldmann, Herbert

    2016-08-17

    Protein lipidation is one of the major post-translational modifications (PTM) of proteins. The attachment of the lipid moiety frequently determines the localization and the function of the lipoproteins. Lipidated proteins participate in many essential biological processes in eukaryotic cells, including vesicular trafficking, signal transduction, and regulation of the immune response. Malfunction of these cellular processes usually leads to various diseases such as cancer. Understanding the mechanism of cellular signaling and identifying the protein-protein and protein-lipid interactions in which the lipoproteins are involved is a crucial task. To achieve these goals, fully functional lipidated proteins are required. However, access to lipoproteins by means of standard expression is often rather limited. Therefore, semisynthetic methods, involving the synthesis of lipidated peptides and their subsequent chemoselective ligation to yield full-length lipoproteins, were developed. In this Review we summarize the commonly used methods for lipoprotein synthesis and the development of the corresponding chemoselective ligation techniques. Several key studies involving full-length semisynthetic lipidated Ras, Rheb, and LC3 proteins are presented.

  4. Lipid functions in skin: Differential effects of n-3 polyunsaturated fatty acids on cutaneous ceramides, in a human skin organ culture model.

    Science.gov (United States)

    Kendall, Alexandra C; Kiezel-Tsugunova, Magdalena; Brownbridge, Luke C; Harwood, John L; Nicolaou, Anna

    2017-09-01

    Ceramides are important for skin health, with a multitude of species found in both dermis and epidermis. The epidermis contains linoleic acid-Ester-linked Omega-hydroxylated ceramides of 6-Hydroxy-sphingosine, Sphingosine and Phytosphingosine bases (CER[EOH], CER[EOS] and CER[EOP], respectively), that are crucial for the formation of the epidermal barrier, conferring protection from environmental factors and preventing trans-epidermal water loss. Furthermore, a large number of ceramides, derivatives of the same sphingoid bases and various fatty acids, are produced by dermal and epidermal cells and perform signalling roles in cell functions ranging from differentiation to apoptosis. Supplementation with the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise as therapeutic agents in a number of inflammatory skin conditions, altering the lipid profile of the skin and production of bioactive lipids such as the eicosanoids, docosanoids and endocannabinoids. In this study we wished to investigate whether EPA and DHA could also affect the ceramide profile in epidermis and dermis, and, in this way, contribute to formation of a robust lipid barrier and ceramide-mediated regulation of skin functions. Ex vivo skin explants were cultured for 6days, and supplemented with EPA or DHA (50μM). Liquid chromatography coupled to tandem mass spectrometry with electrospray ionisation was used to assess the prevalence of 321 individual ceramide species, and a number of sphingoid bases, phosphorylated sphingoid bases, and phosphorylated ceramides, within the dermis and epidermis. EPA augmented dermal production of members of the ceramide families containing Non-hydroxy fatty acids and Sphingosine or Dihydrosphingosine bases (CER[NS] and CER[NDS], respectively), while epidermal CER[EOH], CER[EOS] and CER[EOP] ceramides were not affected. DHA did not significantly affect ceramide production. Ceramide-1-phosphate levels in

  5. Influence of barium substitution on bioactivity, thermal and physico-mechanical properties of bioactive glass

    Energy Technology Data Exchange (ETDEWEB)

    Arepalli, Sampath Kumar, E-mail: askumar.rs.cer11@iitbhu.ac.in; Tripathi, Himanshu; Vyas, Vikash Kumar; Jain, Shubham; Suman, Shyam Kumar; Pyare, Ram; Singh, S.P., E-mail: spsinghceram@gmail.com

    2015-04-01

    Barium with low concentration in the glasses acts as a muscle stimulant and is found in human teeth. We have made a primary study by substituting barium in the bioactive glass. The chemical composition containing (46.1 − X) SiO{sub 2−}–24.3 Na{sub 2}O–26.9 CaO–2.6 P{sub 2}O{sub 5}, where X = 0, 0.4, 0.8, 1.2 and 1.6 mol% of BaO was chosen and melted in an electric furnace at 1400 ± 5 °C. The glasses were characterized to determine their use in biomedical applications. The nucleation and crystallization regimes were determined by DTA and the controlled crystallization was carried out by suitable heat treatment. The crystalline phase formed was identified by using XRD technique. Bioactivity of these glasses was assessed by immersion in simulated body fluid (SBF) for various time periods. The formation of hydroxy carbonate apatite (HCA) layer was identified by FTIR spectrometry, scanning electron microscope (SEM) and XRD which showed the presence of HCA as the main phase in all tested bioactive glass samples. Flexural strength and densities of bioactive glasses have been measured and found to increase with increasing the barium content. The human blood compatibility of the samples was evaluated and found to be pertinent. - Highlights: • In vitro bioactivity of soda-lime–baria-phospho-silicate glass was investigated. • HCA formed on surface of glasses was confirmed by XRD, SEM and FTIR spectrometry. • Mechanical properties of glasses were found to increase with barium addition. • Hemolysis showed that 1.2 mol% BaO bioactive glass exhibited better biocompatibility. • Barium substituted bioactive glasses can be used as bone implants.

  6. Discovery of Bioactive Metabolites in Biofuel Microalgae That Offer Protection against Predatory Bacteria

    Directory of Open Access Journals (Sweden)

    Christopher eBagwell

    2016-04-01

    Full Text Available Microalgae could become an important resource for addressing increasing global demand for food, energy, and commodities while helping to reduce atmospheric greenhouse gases. Even though Chlorophytes are generally regarded safe for human consumption, there is still much we do not understand about the metabolic and biochemical potential of microscopic algae. The aim of this study was to evaluate biofuel candidate strains of Chlorella and Scenedesmus for the potential to produce bioactive metabolites when grown under nutrient depletion regimes intended to stimulate production of triacylglycerides (TAG. Strain specific combinations of macro- and micro-nutrient restricted growth media did stimulate neutral lipid accumulation by microalgal cultures. However, cultures that were restricted for iron consistently and reliably tested positive for cytotoxicity by in vivo bioassays. The addition of iron back to these cultures resulted in the disappearance of the bioactive components by LC/MS fingerprinting and loss of cytotoxicity by in vivo bioassay. Incomplete NMR characterization of the most abundant cytotoxic fractions suggested that small molecular weight peptides and glycosides could be responsible for Chlorella cytotoxicity. Experiments were conducted to determine if the bioactive metabolites induced by Fe-limitation in Chlorella sp. cultures would elicit protection against Vampirovibrio chlorellavorus, an obligate predator of Chlorella. Introduction of V. chlorellavorus resulted in a 72% decrease in algal biomass in the experimental controls after 7 days. Conversely, only slight losses of algal biomass were measured for the iron limited Chlorella cultures (0 - 9 %. This study demonstrates a causal linkage between iron bioavailability and bioactive metabolite production in strains of Chlorella and Scenedesmus. Further study of this phenomenon could contribute to the development of new strategies to extend algal production cycles in open, outdoor

  7. Imbalanced Hemolymph Lipid Levels Affect Feeding Motivation in the Two-Spotted Cricket, Gryllus bimaculatus.

    Directory of Open Access Journals (Sweden)

    Takahiro Konuma

    Full Text Available Insect feeding behavior is regulated by many intrinsic factors, including hemolymph nutrient levels. Adipokinetic hormone (AKH is a peptide factor that modulates hemolymph nutrient levels and regulates the nutritional state of insects by triggering the transfer of lipids into the hemolymph. We recently demonstrated that RNA interference (RNAi-mediated knockdown of the AKH receptor (AKHR reduces hemolymph lipid levels, causing an increase in the feeding frequency of the two-spotted cricket, Gryllus bimaculatus. This result indicated that reduced hemolymph lipid levels might motivate crickets to feed. In the present study, to elucidate whether hemolymph lipid levels contribute to insect feeding behavior, we attempted to manipulate hemolymph lipid levels via the lipophorin (Lp-mediated lipid transferring system in G. bimaculatus. Of the constituent proteins in Lp, we focused on apolipophorin-III (GrybiApoLp-III because of its possible role in facilitating lipid mobilization. First, we used RNAi to reduce the expression of GrybiApoLp-III. RNAi-mediated knockdown of GrybiApoLp-III had little effect on basal hemolymph lipid levels and the amount of food intake. In addition, hemolymph lipid levels remained static even after injecting AKH into GrybiApoLp-IIIRNAi crickets. These observations indicated that ApoLp-III does not maintain basal hemolymph lipid levels in crickets fed ad libitum, but is necessary for mobilizing lipid transfer into the hemolymph following AKH stimulation. Second, Lp (containing lipids was injected into the hemolymph to induce a temporary increase in hemolymph lipid levels. Consequently, the initiation of feeding was delayed in a dose-dependent manner, indicating that increased hemolymph lipid levels reduced the motivation to feed. Taken together, these data validate the importance of basal hemolymph lipid levels in the control of energy homeostasis and for regulating feeding behavior in crickets.

  8. Perspectives on marine zooplankton lipids

    DEFF Research Database (Denmark)

    Kattner, G.; Hagen, W.; Lee, R.F.

    2007-01-01

    We developed new perspectives to identify important questions and to propose approaches for future research on marine food web lipids. They were related to (i) structure and function of lipids, (ii) lipid changes during critical life phases, (iii) trophic marker lipids, and (iv) potential impact...... of climate change. The first addresses the role of lipids in membranes, storage lipids, and buoyancy with the following key question: How are the properties of membranes and deposits affected by the various types of lipids? The second deals with the importance of various types of lipids during reproduction......, development, and resting phases and addresses the role of the different storage lipids during growth and dormancy. The third relates to trophic marker lipids, which are an important tool to follow lipid and energy transfer through the food web. The central question is how can fatty acids be used to identify...

  9. Unusual lipid structures selectively reduce the toxicity of amphotericin B

    International Nuclear Information System (INIS)

    Janoff, A.S.; Boni, L.T.; Popescu, M.C.

    1988-01-01

    Ribbon-like structures result when amphotericin B interacts with lipid in an aqueous environment. At high ratios of amphotericin to lipid these structures, which are lipid-stabilized amphotericin aggregates, become prevalent resulting in a dramatic attenuation of amphotericin-mediated mammalian cell, but not fungal cell, toxicity. Studies utilizing freeze-etch electron microscopy, differential scanning calorimetry, 31 P NMR, x-ray diffraction, and optical spectroscopy revealed that this toxicity attenuation is related to the macromolecular structure of the complexes in a definable fashion. It is likely that amphotericin in this specific form will have a much improved therapeutic utility

  10. A novel theory: biological processes mostly involve two types of mediators, namely general and specific mediators Endogenous small radicals such as superoxide and nitric oxide may play a role of general mediator in biological processes.

    Science.gov (United States)

    Mo, Jian

    2005-01-01

    A great number of papers have shown that free radicals as well as bioactive molecules can play a role of mediator in a wide spectrum of biological processes, but the biological actions and chemical reactivity of the free radicals are quite different from that of the bioactive molecules, and that a wide variety of bioactive molecules can be easily modified by free radicals due to having functional groups sensitive to redox, and the significance of the interaction between the free radicals and the bioactive molecules in biological processes has been confirmed by the results of some in vitro and in vivo studies. Based on these evidence, this article presented a novel theory about the mediators of biological processes. The essentials of the theory are: (a) mediators of biological processes can be classified into general and specific mediators; the general mediators include two types of free radicals, namely superoxide and nitric oxide; the specific mediators include a wide variety of bioactive molecules, such as specific enzymes, transcription factors, cytokines and eicosanoids; (b) a general mediator can modify almost any class of the biomolecules, and thus play a role of mediator in nearly every biological process via diverse mechanisms; a specific mediator always acts selectively on certain classes of the biomolecules, and may play a role of mediator in different biological processes via a same mechanism; (c) biological processes are mostly controlled by networks of their mediators, so the free radicals can regulate the last consequence of a biological process by modifying some types of the bioactive molecules, or in cooperation with these bioactive molecules; the biological actions of superoxide and nitric oxide may be synergistic or antagonistic. According to this theory, keeping the integrity of these networks and the balance between the free radicals and the bioactive molecules as well as the balance between the free radicals and the free radical scavengers

  11. Bioactive Compounds in Functional Meat Products.

    Science.gov (United States)

    Pogorzelska-Nowicka, Ewelina; Atanasov, Atanas G; Horbańczuk, Jarosław; Wierzbicka, Agnieszka

    2018-01-31

    Meat and meat products are a good source of bioactive compounds with positive effect on human health such as vitamins, minerals, peptides or fatty acids. Growing food consumer awareness and intensified global meat producers competition puts pressure on creating new healthier meat products. In order to meet these expectations, producers use supplements with functional properties for animal diet and as direct additives for meat products. In the presented work seven groups of key functional constituents were chosen: (i) fatty acids; (ii) minerals; (iii) vitamins; (iv) plant antioxidants; (v) dietary fibers; (vi) probiotics and (vii) bioactive peptides. Each of them is discussed in term of their impact on human health as well as some quality attributes of the final products.

  12. Microgreens: Production, shelf life, and bioactive components.

    Science.gov (United States)

    Mir, Shabir Ahmad; Shah, Manzoor Ahmad; Mir, Mohammad Maqbool

    2017-08-13

    Microgreens are emerging specialty food products which are gaining popularity and increased attention nowadays. They are young and tender cotyledonary leafy greens that are found in a pleasing palette of colors, textures, and flavors. Microgreens are a new class of edible vegetables harvested when first leaves have fully expanded and before true leaves have emerged. They are gaining popularity as a new culinary ingredient. They are used to enhance salads or as edible garnishes to embellish a wide variety of other dishes. Common microgreens are grown mainly from mustard, cabbage, radish, buckwheat, lettuce, spinach, etc. The consumption of microgreens has nowadays increased due to higher concentrations of bioactive components such as vitamins, minerals, and antioxidants than mature greens, which are important for human health. However, they typically have a short shelf life due to rapid product deterioration. This review aimed to evaluate the postharvest quality, potential bioactive compounds, and shelf life of microgreens for proper management of this specialty produce.

  13. A new look at lipid-membrane structure in relation to drug research

    DEFF Research Database (Denmark)

    Mouritsen, Ole G.; Jørgensen, Kent

    1998-01-01

    Lipid-bilayer membranes are key objects in drug research in relation to (i) interaction of drugs with membrane-bound receptors, (ii) drug targeting, penetration, and permeation of cell membranes, and (iii) use of liposomes in micro-encapsulation technologies for drug delivery. Rational design...... of new drugs and drug-delivery systems therefore requries insight into the physical properties of lipid-bilayer membranes. This mini-review provides a perspective on the current view of lipid-bilayer structure and dynamics based on information obtained from a variety of recent experimental...... and theoretical studies. Special attention is paid to trans-bilayer structure, lateral molecular organization of the lipid bilayer, lipid-mediated protein assembly, and lipid-bilayer permeability. It is argued that lipids play a major role in lipid membrane-organization and functionality....

  14. The role of red blood cell S-nitrosation in nitrite bioactivation and its modulation by leucine and glucose

    Directory of Open Access Journals (Sweden)

    Nadeem Wajih

    2016-08-01

    Full Text Available Previous work has shown that red blood cells (RBCs reduce nitrite to NO under conditions of low oxygen. Strong support for the ability of red blood cells to promote nitrite bioactivation comes from using platelet activation as a NO-sensitive process. Whereas addition of nitrite to platelet rich plasma in the absence of RBCs has no effect on inhibition of platelet activation, when RBCs are present platelet activation is inhibited by an NO-dependent mechanism that is potentiated under hypoxia. In this paper, we demonstrate that nitrite bioactivation by RBCs is blunted by physiologically-relevant concentrations of nutrients including glucose and the important signaling amino acid leucine. Our mechanistic investigations demonstrate that RBC mediated nitrite bioactivation is largely dependent on nitrosation of RBC surface proteins. These data suggest a new expanded paradigm where RBC mediated nitrite bioactivation not only directs blood flow to areas of low oxygen but also to areas of low nutrients. Our findings could have profound implications for normal physiology as well as pathophysiology in a variety of diseases including diabetes, sickle cell disease, and arteriosclerosis.

  15. Nanoencapsulation of bioactive compounds for food applications

    OpenAIRE

    Sessa, Mariarenata

    2012-01-01

    2010 - 2011 The increase in dietary-intake-related illnesses, such as obesity, cardiovascular diseases, hypertension, diabetes and cancer, have made in recent years the development of health-and-wellness promoting foods a priority of the food industry. Clinical studies have demonstrated tangible health benefits that may be derived from the intake of bioactive compounds. However many difficulties are associated with their inclusion in food matrices, due to a very low solubility in water and...

  16. Bioactive Compounds in Functional Meat Products

    OpenAIRE

    Ewelina Pogorzelska-Nowicka; Atanas G. Atanasov; Jarosław Horbańczuk; Agnieszka Wierzbicka

    2018-01-01

    Meat and meat products are a good source of bioactive compounds with positive effect on human health such as vitamins, minerals, peptides or fatty acids. Growing food consumer awareness and intensified global meat producers competition puts pressure on creating new healthier meat products. In order to meet these expectations, producers use supplements with functional properties for animal diet and as direct additives for meat products. In the presented work seven groups of key functional cons...

  17. Secondary metabolites and bioactivities of Myrtus communis

    OpenAIRE

    Mahmoud I Nassar; El-Sayed A Aboutabl; Rania F Ahmed; Ezzel-Din A El-Khrisy; Khaled M Ibrahim; Amany A Sleem

    2010-01-01

    Background: Myrtus species are characterized by the presence of phenolic acids, flavonoids, tannins, volatile oils and fatty acids. They are remedies for variety of ailments. This study therefore investigated medicinal effects of Myrtus communis L. Methods: Bioactivity studies of Myrtus communis L. leaves were carried out on volatile oil, 7% methanol and aqueous extracts and the isolated compounds myricetin 3-O-β-glucopyranoside, myricetin 3-O-∝-rhamnopyranoside and gallic acid. Results: Dete...

  18. Seminal Fluid-Mediated Inflammation in Physiology and Pathology of the Female Reproductive Tract

    Directory of Open Access Journals (Sweden)

    Anthonio O. Adefuye

    2016-01-01

    Full Text Available Inflammation is a multifaceted process involving a host of resident and recruited immune cells that eliminate the insult or injury and initiate tissue repair. In the female reproductive tract (FMRT, inflammation-mediated alterations in epithelial, vascular, and immune functions are important components of complex physiological processes and many local and systemic pathologies. It is well established that intracoital and postcoital function of seminal fluid (SF goes beyond nutritive support for the spermatozoa cells. SF, in particular, the inflammatory bioactive lipids, and prostaglandins present in vast quantities in SF, have a role in localized immune modulation and regulation of pathways that can exacerbate inflammation in the FMRT. In sexually active women SF-mediated inflammation has been implicated in physiologic processes such as ovulation, implantation, and parturition while also enhancing tumorigenesis and susceptibility to infection. This review highlights the molecular mechanism by which SF regulates inflammatory pathways in the FMRT and how alterations in these pathways contribute to physiology and pathology of the female reproductive function. In addition, based on findings from TaqMan® 96-Well Plate Arrays, on neoplastic cervical cells treated with SF, we discuss new findings on the role of SF as a potent driver of inflammatory and tumorigenic pathways in the cervix.

  19. Analysis of commercial and public bioactivity databases.

    Science.gov (United States)

    Tiikkainen, Pekka; Franke, Lutz

    2012-02-27

    Activity data for small molecules are invaluable in chemoinformatics. Various bioactivity databases exist containing detailed information of target proteins and quantitative binding data for small molecules extracted from journals and patents. In the current work, we have merged several public and commercial bioactivity databases into one bioactivity metabase. The molecular presentation, target information, and activity data of the vendor databases were standardized. The main motivation of the work was to create a single relational database which allows fast and simple data retrieval by in-house scientists. Second, we wanted to know the amount of overlap between databases by commercial and public vendors to see whether the former contain data complementing the latter. Third, we quantified the degree of inconsistency between data sources by comparing data points derived from the same scientific article cited by more than one vendor. We found that each data source contains unique data which is due to different scientific articles cited by the vendors. When comparing data derived from the same article we found that inconsistencies between the vendors are common. In conclusion, using databases of different vendors is still useful since the data overlap is not complete. It should be noted that this can be partially explained by the inconsistencies and errors in the source data.

  20. A new bio-active glass ceramic

    International Nuclear Information System (INIS)

    Shamim, A.; Arif, I.; Suleman, M.; Hussain, K.; Shah, W.A.

    1995-01-01

    Since 1960 fine ceramics such as alumina have been used side by side with metallic materials for bone and joint replacement. They have high mechanical strength and are free from corrosion problem faced by metals. However they don't bond to the natural living bone and hence are called bio-inactive. This was followed by the development of bio-active glasses and glass-ceramics which bond to the natural bone but have low mechanical strength. In the present work a new bio-active glass-ceramic, based on CaO-SiO/sub 2/-P/sub 2/O/sub 3/-MgO composition, has been developed which has mechanical strength compared to that of a bio-inactive glass ceramic and also bonds strongly to the natural bone. X-ray diffraction analysis reveals wollastanite and apatite phases in the glass ceramic. A new bio-active cement has also been developed which can be used to join broken pieces of bone or by itself at a filler. (author)

  1. Adhesive Bioactive Coatings Inspired by Sea Life.

    Science.gov (United States)

    Rego, Sónia J; Vale, Ana C; Luz, Gisela M; Mano, João F; Alves, Natália M

    2016-01-19

    Inspired by nature, in particular by the marine mussels adhesive proteins (MAPs) and by the tough brick-and-mortar nacre-like structure, novel multilayered films are prepared in the present work. Organic-inorganic multilayered films, with an architecture similar to nacre based on bioactive glass nanoparticles (BG), chitosan, and hyaluronic acid modified with catechol groups, which are the main components responsible for the outstanding adhesion in MAPs, are developed for the first time. The biomimetic conjugate is prepared by carbodiimide chemistry and analyzed by ultraviolet-visible spectrophotometry. The buildup of the multilayered films is monitored with a quartz crystal microbalance with dissipation monitoring, and their topography is characterized by atomic force microscopy. The mechanical properties reveal that the films containing catechol groups and BG present an enhanced adhesion. Moreover, the bioactivity of the films upon immersion in a simulated body fluid solution is evaluated by scanning electron microscopy coupled with energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. It was found that the constructed films promote the formation of bonelike apatite in vitro. Such multifunctional mussel inspired LbL films, which combine enhanced adhesion and bioactivity, could be potentially used as coatings of a variety of implants for orthopedic applications.

  2. Human Milk Composition: Nutrients and Bioactive Factors

    Science.gov (United States)

    Ballard, Olivia; Morrow, Ardythe L.

    2013-01-01

    Synopsis The composition of human milk is the biologic norm for infant nutrition. Human milk also contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Some of these molecules, e.g., lactoferrin, are being investigated as novel therapeutic agents. A dynamic, bioactive fluid, human milk changes in composition from colostrum to late lactation, and varies within feeds, diurnally, and between mothers. Feeding infants with expressed human milk is increasing. Pasteurized donor milk is now commonly provided to high risk infants and most mothers in the U.S. express and freeze their milk at some point in lactation for future infant feedings. Many milk proteins are degraded by heat treatment and freeze-thaw cycles may not have the same bioactivity after undergoing these treatments. This article provides an overview of the composition of human milk, sources of its variation, and its clinical relevance. PMID:23178060

  3. Ultrasound assisted extraction of bioactive compounds

    Directory of Open Access Journals (Sweden)

    Helena Drmić

    2010-01-01

    Full Text Available Many novel and innovative techniques are nowadays researched and explored in order to replace or improve classical, thermal processing technologies. One of newer technique is technique of minimal food processing, under what we assume ultrasound processing. Ultrasound technology can be very useful for minimal food processing because transmission of acoustic energy through product is fast and complete, which allows reduction in total processing time, and therefore lower energy consumption. Industrial processing is growing more and more waste products, and in desire of preservation of global recourses and energy efficiency, several ways of active compounds extraction techniques are now explored. The goal is to implement novel extraction techniques in food and pharmaceutical industry as well in medicine. Ultrasound assisted extraction of bioactive compounds offers increase in yield, and reduction or total avoiding of solvent usage. Increase in temperature of treatment is controlled and restricted, thereby preserving extracted bioactive compounds. In this paper, several methods of ultrasound assisted extraction of bioactive compounds from plant materials are shown. Ultrasound can improve classic mechanisms of extraction, and thereby offer novel possibilities of commercial extraction of desired compounds. Application of sonochemistry (ultrasound chemistry is providing better yield in desired compounds and reduction in treatment time.

  4. Acyl-Lipid Metabolism

    Science.gov (United States)

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2013-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

  5. Hippocampal lipid differences in Alzheimer's disease: a human brain study using matrix?assisted laser desorption/ionization?imaging mass spectrometry

    OpenAIRE

    Mendis, Lakshini H. S.; Grey, Angus C.; Faull, Richard L. M.; Curtis, Maurice A.

    2016-01-01

    Abstract Introduction Alzheimer's disease (AD), the leading cause of dementia, is pathologically characterized by ??amyloid plaques and tau tangles. However, there is also evidence of lipid dyshomeostasis?mediated AD pathology. Given the structural diversity of lipids, mass spectrometry is a useful tool for studying lipid changes in AD. Although there have been a few studies investigating lipid changes in the human hippocampus in particular, there are few reports on how lipids change in each ...

  6. EFFECTS OF INCORPORATING NATURAL MINERALS ON PRODUCTION AND BIOACTIVITY OF BIOACTIVE GLASS CERAMICS

    Directory of Open Access Journals (Sweden)

    Franco Matias Stabile

    2016-07-01

    Full Text Available Two glass-ceramics composition were produced from natural minerals. Quartzes and feldspars were pre-selected on the basis of their purities studied by X-ray diffraction (XRD and chemical analysis. Prepared compositions of glasses precursors were two different theoretical leucite (KAlSi₂O₆ /Bioglass 45S5 (L/Bg ratios. Transformations of raw materials mixtures and glass precursors were studied by differential thermal analyses. On the basis of thermal analysis results, glass ceramics were produced and characterized by XRD. Glass-ceramics were composed of two major crystalline phases, leucite and sodium calcium silicate. Bioactivity tests were performed submerging the glass-ceramics into simulated body fluid (SBF for different periods (1, 5 and 10 days. Bioactive behavior was monitored by XRD and scanning electron microscopy (SEM. Studied samples were found to be bioactive, in which hydroxyapatite layer was developed within 5 days of contact with SBF.

  7. Assay of mast cell mediators

    DEFF Research Database (Denmark)

    Rådinger, Madeleine; Jensen, Bettina M; Swindle, Emily

    2015-01-01

    Mediator release from activated mast cells is a major initiator of the symptomology associated with allergic disorders such as anaphylaxis and asthma. Thus, methods to monitor the generation and release of such mediators have widespread applicability in studies designed to understand the processes...... regulating mast cell activation and for the identification of therapeutic approaches to block mast cell-driven disease. In this chapter, we discuss approaches used for the determination of mast cell degranulation, lipid-derived inflammatory mediator production, and cytokine/chemokine gene expression as well...

  8. Bioactive glasses and glass-ceramics

    Directory of Open Access Journals (Sweden)

    de Aza, P. N.

    2007-04-01

    Full Text Available Since the late 1960´s, a great interest in the use of bioceramic materials for biomedical applications has been developed. In a previous paper, the authors reviewed crystalline bioceramic materials “sensus stricto”, it is to say, those ceramic materials, constituted for non-metallic inorganic compounds, crystallines and consolidates by thermal treatment of powders at high temperature. In the present review, the authors deal with those called bioactive glasses and glassceramics. Although all of them are also obtained by thermal treatment at high temperature, the first are amorphous and the second are obtained by devitrification of a glass, although the vitreous phase normally prevails on the crystalline phases. After an introduction to the concept of bioactive materials, a short historical review of the bioactive glasses development is made. Its preparation, reactivity in physiological media, mechanism of bonding to living tissues and mechanical strength of the bone-implant interface is also reported. Next, the concept of glass-ceramic and the way of its preparation are exposed. The composition, physicochemical properties and biological behaviour of the principal types of bioactive glasses and glass-ceramic materials: Bioglass®, Ceravital®, Cerabone®, Ilmaplant® and Bioverit® are also reviewed. Finally, a short review on the bioactive-glass coatings and bioactive-composites and most common uses of bioactive-glasses and glass-ceramics are carried out too.

    Desde finales de los años sesenta, se ha despertado un gran interés por el uso de los materiales biocerámicos para aplicaciones biomédicas. En un trabajo previo, los autores hicieron una revisión de los denominados materiales biocerámicos cristalinos en sentido estricto, es decir, de aquellos materiales, constituidos por compuestos inorgánicos no metálicos, cristalinos y consolidados mediante tratamientos térmicos a altas temperaturas. En el presente trabajo, los autores

  9. Bioactivity and properties of a dental adhesive functionalized with polyhedral oligomeric silsesquioxanes (POSS) and bioactive glass.

    Science.gov (United States)

    Rizk, Marta; Hohlfeld, Lisa; Thanh, Loan Tao; Biehl, Ralf; Lühmann, Nicole; Mohn, Dirk; Wiegand, Annette

    2017-09-01

    This study aimed to analyze the effect of infiltrating a commercial adhesive with nanosized bioactive glass (BG-Bi) particles or methacryl-functionalized polyhedral oligomeric silsesquioxanes (POSS) on material properties and bioactivity. An acetone-based dental adhesive (Solobond Plus adhesive, VOCO GmbH, Cuxhaven, Germany) was infiltrated with nanosized bioactive glass particles (0.1 or 1wt%), or with monofunctional or multifunctional POSS particles (10 or 20wt%). Unfilled adhesive served as control. Dispersion and hydrodynamic radius of the nanoparticles were studied by dynamic light scattering. Set specimens were immersed for 28days in artificial saliva at 37°C, and surfaces were mapped for the formation of calcium phospate (Ca/P) precipitates (scanning electron microscopy/energy-dispersive X-ray spectroscopy). Viscosity (rheometry) and the structural characteristic of the networks were studied, such as degree of conversion (FTIR spectroscopy), sol fraction and water sorption. POSS particles showed a good dispersion of the particles for both types of particles being smaller than 3nm, while the bioactive glass particles had a strong tendency to agglomerate. All nanoparticles induced the formation of Ca/P precipitates. The viscosity of the adhesive was not or only slightly increased by POSS particle addition but strongly increased by the bioactive glass particles. The degree of conversion, water sorption and sol fraction showed a maintained or improved network structure and properties when filled with BG-Bi and multifunctional POSS, however, less polymerization was found when loading a monofunctional POSS. Multifunctional POSS may be incorporated into dental adhesives to provide a bioactive potential without changing material properties adversely. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  10. Bioactive glass coupling with natural polyphenols: Surface modification, bioactivity and anti-oxidant ability

    Energy Technology Data Exchange (ETDEWEB)

    Cazzola, Martina [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy); Corazzari, Ingrid [Università degli Studi di Torino, Department of Chemistry, Via Pietro Giuria 7, Torino 10125 (Italy); Centro Interdipartimentale “G. Scansetti” per lo studio degli amianti e di altri particolati nocivi, Via Pietro Giuria 9, 10125 Torino (Italy); Prenesti, Enrico [Università degli Studi di Torino, Department of Chemistry, Via Pietro Giuria 7, Torino 10125 (Italy); Bertone, Elisa [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy); Vernè, Enrica, E-mail: enrica.verne@polito.it [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy); Ferraris, Sara [Politecnico di Torino, Department of Applied Science and Technology, Institute of Materials Physics and Engineering, C.so Duca degli Abruzzi 24, Torino 10129 (Italy)

    2016-03-30

    Graphical abstract: - Highlights: • Surface functionalization of bioactive glass with biomolecules has been optimized. • Biomolecules are present and active on the glass surface after functionalization. • Biomolecules affect deposition kinetics and morphology of hydroxyapatite. • Free radical scavenging activity is seen for the first time on bioactive glasses. - Abstract: Polyphenols are actually achieving an increasing interest due to their potential health benefits, such as antioxidant, anticancer, antibacterial and bone stimulation abilities. However their poor bioavailability and stability hamper an effective clinical application as therapeutic principles. The opportunity to couple these biomolecules with synthetic biomaterials, in order to obtain local delivery at the site of interest, improve their bioavailability and stability and combine their properties with the ones of the substrate, is a challenging opportunity for the biomedical research. A silica based bioactive glass, CEL2, has been successfully coupled with gallic acid and natural polyphenols extracted from red grape skins and green tea leaves. The effectiveness of grafting has been verified by means of XPS analyses and the Folin&Ciocalteu tests. In vitro bioactivity has been investigated by soaking in simulated body fluid (SBF). Surface modification after functionalization and early stage reactivity in SBF have been studied by means of zeta potential electrokinetic measurements in KCl and SBF. Finally the antioxidant properties of bare and modified bioactive glasses has been investigated by means of the evaluation of free radical scavenging activity by Electron Paramagnetic Resonance (EPR)/spin trapping technique after UV photolysis of H{sub 2}O{sub 2} highlighting scavenging activity of the bioactive glass.

  11. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  12. Plasma membrane lipids and their role in fungal virulence.

    Science.gov (United States)

    Rella, Antonella; Farnoud, Amir M; Del Poeta, Maurizio

    2016-01-01

    There has been considerable evidence in recent years suggesting that plasma membrane lipids are important regulators of fungal pathogenicity. Various glycolipids have been shown to impart virulent properties in several fungal species, while others have been shown to play a role in host defense. In addition to their role as virulence factors, lipids also contribute to other virulence mechanisms such as drug resistance, biofilm formation, and release of extracellular vesicles. In addition, lipids also affect the mechanical properties of the plasma membrane through the formation of packed microdomains composed mainly of sphingolipids and sterols. Changes in the composition of lipid microdomains have been shown to disrupt the localization of virulence factors and affect fungal pathogenicity. This review gathers evidence on the various roles of plasma membrane lipids in fungal virulence and how lipids might contribute to the different processes that occur during infection and treatment. Insight into the role of lipids in fungal virulence can lead to an improved understanding of the process of fungal pathogenesis and the development of new lipid-mediated therapeutic strategies. Published by Elsevier Ltd.

  13. The Correlation of Pore Size and Bioactivity of Spray-Pyrolyzed Mesoporous Bioactive Glasses

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chou

    2017-05-01

    Full Text Available SiO2–CaO–P2O5-based mesoporous bioactive glasses (MBGs were synthesized by spray pyrolysis in this study. Three commonly used non-ionic tri-block copolymers (L121, P123, and F127 with various lengths of hydrophilic chains were applied as structural templates to achieve different pore sizes. A mesoporous structure was observed in each as-prepared specimen, and the results showed that the L121-treated MBG had the largest pore size. The results of bioactivity tests indicated that the growth of hydroxyapatite is related to the pore size of the materials.

  14. Interaction pathways between soft lipid nanodiscs and plasma membranes: A molecular modeling study.

    Science.gov (United States)

    Li, Shixin; Luo, Zhen; Xu, Yan; Ren, Hao; Deng, Li; Zhang, Xianren; Huang, Fang; Yue, Tongtao

    2017-10-01

    Lipid nanodisc, a model membrane platform originally synthesized for study of membrane proteins, has recently been used as the carrier to deliver amphiphilic drugs into target tumor cells. However, the central question of how cells interact with such emerging nanomaterials remains unclear and deserves our research for both improving the delivery efficiency and reducing the side effect. In this work, a binary lipid nanodisc is designed as the minimum model to investigate its interactions with plasma membranes by using the dissipative particle dynamics method. Three typical interaction pathways, including the membrane attachment with lipid domain exchange of nanodiscs, the partial membrane wrapping with nanodisc vesiculation, and the receptor-mediated endocytosis, are discovered. For the first pathway, the boundary normal lipids acting as ligands diffuse along the nanodisc rim to gather at the membrane interface, repelling the central bola lipids to reach a stable membrane attachment. If bola lipids are positioned at the periphery and act as ligands, they diffuse to form a large aggregate being wrapped by the membrane, leaving the normal lipids exposed on the membrane exterior by assembling into a vesicle. Finally, by setting both central normal lipids and boundary bola lipids as ligands, the receptor-mediated endocytosis occurs via both deformation and self-rotation of the nanodiscs. All above pathways for soft lipid nanodiscs are quite different from those for rigid nanoparticles, which may provide useful guidelines for design of soft lipid nanodiscs in widespread biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Membrane Contact Sites: Complex Zones for Membrane Association and Lipid Exchange

    Science.gov (United States)

    Quon, Evan; Beh, Christopher T.

    2015-01-01

    Lipid transport between membranes within cells involves vesicle and protein carriers, but as agents of nonvesicular lipid transfer, the role of membrane contact sites has received increasing attention. As zones for lipid metabolism and exchange, various membrane contact sites mediate direct associations between different organelles. In particular, membrane contact sites linking the plasma membrane (PM) and the endoplasmic reticulum (ER) represent important regulators of lipid and ion transfer. In yeast, cortical ER is stapled to the PM through membrane-tethering proteins, which establish a direct connection between the membranes. In this review, we consider passive and facilitated models for lipid transfer at PM–ER contact sites. Besides the tethering proteins, we examine the roles of an additional repertoire of lipid and protein regulators that prime and propagate PM–ER membrane association. We conclude that instead of being simple mediators of membrane association, regulatory components of membrane contact sites have complex and multilayered functions. PMID:26949334

  16. Lipid Cell Biology: A Focus on Lipids in Cell Division.

    Science.gov (United States)

    Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S

    2018-06-20

    Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

  17. Protein/lipid coaggregates are formed during α-synuclein-induced disruption of lipid bilayers

    DEFF Research Database (Denmark)

    van Maarschalkerweerd, Andreas; Vetri, Valeria; Langkilde, Annette Eva

    2014-01-01

    Amyloid formation is associated with neurodegenerative diseases such as Parkinson's disease (PD). Significant α-synuclein (αSN) deposition in lipid-rich Lewy bodies is a hallmark of PD. Nonetheless, an unraveling of the connection between neurodegeneration and amyloid fibrils, including the molec......Amyloid formation is associated with neurodegenerative diseases such as Parkinson's disease (PD). Significant α-synuclein (αSN) deposition in lipid-rich Lewy bodies is a hallmark of PD. Nonetheless, an unraveling of the connection between neurodegeneration and amyloid fibrils, including...... the molecular mechanisms behind potential amyloid-mediated toxic effects, is still missing. Interaction between amyloid aggregates and the lipid cell membrane is expected to play a key role in the disease progress. Here, we present experimental data based on hybrid analysis of two-photon-microscopy, solution...... small-angle X-ray scattering and circular dichroism data. Data show in real time changes in liposome morphology and stability upon protein addition and reveal that membrane disruption mediated by amyloidogenic αSN is associated with dehydration of anionic lipid membranes and stimulation of protein...

  18. Alkali-free bioactive glasses for bone regeneration

    OpenAIRE

    Kapoor, Saurabh

    2014-01-01

    Bioactive glasses and glass-ceramics are a class of third generation biomaterials which elicit a special response on their surface when in contact with biological fluids, leading to strong bonding to living tissues. The purpose of the present study was to develop diopside based alkali-free bioactive glasses in order to achieve good sintering behaviour, high bioactivity, and a dissolution/ degradation rates compatible with the target applications in bone regeneration and tiss...

  19. Hierarchically Nanoporous Bioactive Glasses for High Efficiency Immobilization of Enzymes

    DEFF Research Database (Denmark)

    He, W.; Min, D.D.; Zhang, X.D.

    2014-01-01

    Bioactive glasses with hierarchical nanoporosity and structures have been heavily involved in immobilization of enzymes. Because of meticulous design and ingenious hierarchical nanostructuration of porosities from yeast cell biotemplates, hierarchically nanostructured porous bioactive glasses can...... and products of catalytic reactions can freely diffuse through open mesopores (2–40 nm). The formation mechanism of hierarchically structured porous bioactive glasses, the immobilization mechanism of enzyme and the catalysis mechanism of immobilized enzyme are then discussed. The novel nanostructure...

  20. Protein-lipid nanohybrids as emerging platforms for drug and gene delivery: Challenges and outcomes.

    Science.gov (United States)

    Gaber, Mohamed; Medhat, Waseem; Hany, Mark; Saher, Nourhan; Fang, Jia-You; Elzoghby, Ahmed

    2017-05-28

    Nanoparticulate drug delivery systems have been long used to deliver a vast range of drugs and bioactives owing to their ability to demonstrate novel physical, chemical, and/or biological properties. An exponential growth has spurred in research and development of these nanocarriers which led to the evolution of a great number of diverse nanosystems including liposomes, nanoemulsions, solid lipid nanoparticles (SLNs), micelles, dendrimers, polymeric nanoparticles (NPs), metallic NPs, and carbon nanotubes. Among them, lipid-based nanocarriers have made the largest progress whether commercially or under development. Despite this progress, these lipid-based nanocarriers suffer from several limitations that led to the development of many protein-coated lipid nanocarriers. To less extent, protein-based nanocarriers suffer from limitations that led to the fabrication of some lipid bilayer enveloping protein nanocarriers. This review discusses in-depth some limitations associated with the lipid-based or protein-based nanocarriers and the fruitful outcomes brought by protein-lipid hybridization. Also discussed are the various hybridization techniques utilized to formulate these protein-lipid nanohybrids and the mechanisms involved in the drug loading process. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Pharmacogenetics of lipid diseases

    Directory of Open Access Journals (Sweden)

    Ordovas Jose M

    2004-01-01

    Full Text Available Abstract The genetic basis for most of the rare lipid monogenic disorders have been elucidated, but the challenge remains in determining the combination of genes that contribute to the genetic variability in lipid levels in the general population; this has been estimated to be in the range of 40-60 per cent of the total variability. Therefore, the effect of common polymorphisms on lipid phenotypes will be greatly modulated by gene-gene and gene-environment interactions. This approach can also be used to characterise the individuality of the response to lipid-lowering therapies, whether using drugs (pharmacogenetics or dietary interventions (nutrigenetics. In this regard, multiple studies have already described significant interactions between candidate genes for lipid and drug metabolism that modulate therapeutic response--although the outcomes of these studies have been controversial and call for more rigorous experimental design and analytical approaches. Once solid evidence about the predictive value of genetic panels is obtained, risk and therapeutic algorithms can begin to be generated that should provide an accurate measure of genetic predisposition, as well as targeted behavioural modifications or drugs of choice and personalised dosages of these drugs.

  2. Extended synaptotagmins are Ca2+-dependent lipid transfer proteins at membrane contact sites.

    Science.gov (United States)

    Yu, Haijia; Liu, Yinghui; Gulbranson, Daniel R; Paine, Alex; Rathore, Shailendra S; Shen, Jingshi

    2016-04-19

    Organelles are in constant communication with each other through exchange of proteins (mediated by trafficking vesicles) and lipids [mediated by both trafficking vesicles and lipid transfer proteins (LTPs)]. It has long been known that vesicle trafficking can be tightly regulated by the second messenger Ca(2+), allowing membrane protein transport to be adjusted according to physiological demands. However, it remains unclear whether LTP-mediated lipid transport can also be regulated by Ca(2+) In this work, we show that extended synaptotagmins (E-Syts), poorly understood membrane proteins at endoplasmic reticulum-plasma membrane contact sites, are Ca(2+)-dependent LTPs. Using both recombinant and endogenous mammalian proteins, we discovered that E-Syts transfer glycerophospholipids between membrane bilayers in the presence of Ca(2+) E-Syts use their lipid-accommodating synaptotagmin-like mitochondrial lipid binding protein (SMP) domains to transfer lipids. However, the SMP domains themselves cannot transport lipids unless the two membranes are tightly tethered by Ca(2+)-bound C2 domains. Strikingly, the Ca(2+)-regulated lipid transfer activity of E-Syts was fully recapitulated when the SMP domain was fused to the cytosolic domain of synaptotagmin-1, the Ca(2+)sensor in synaptic vesicle fusion, indicating that a common mechanism of membrane tethering governs the Ca(2+)regulation of lipid transfer and vesicle fusion. Finally, we showed that microsomal vesicles isolated from mammalian cells contained robust Ca(2+)-dependent lipid transfer activities, which were mediated by E-Syts. These findings established E-Syts as a novel class of LTPs and showed that LTP-mediated lipid trafficking, like vesicular transport, can be subject to tight Ca(2+)regulation.

  3. Cellular Lipid Extraction for Targeted Stable Isotope Dilution Liquid Chromatography-Mass Spectrometry Analysis

    Science.gov (United States)

    Gelhaus, Stacy L.; Mesaros, A. Clementina; Blair, Ian A.

    2011-01-01

    The metabolism of fatty acids, such as arachidonic acid (AA) and linoleic acid (LA), results in the formation of oxidized bioactive lipids, including numerous stereoisomers1,2. These metabolites can be formed from free or esterified fatty acids. Many of these oxidized metabolites have biological activity and have been implicated in various diseases including cardiovascular and neurodegenerative diseases, asthma, and cancer3-7. Oxidized bioactive lipids can be formed enzymatically or by reactive oxygen species (ROS). Enzymes that metabolize fatty acids include cyclooxygenase (COX), lipoxygenase (LO), and cytochromes P450 (CYPs)1,8. Enzymatic metabolism results in enantioselective formation whereas ROS oxidation results in the racemic formation of products. While this protocol focuses primarily on the analysis of AA- and some LA-derived bioactive metabolites; it could be easily applied to metabolites of other fatty acids. Bioactive lipids are extracted from cell lysate or media using liquid-liquid (l-l) extraction. At the beginning of the l-l extraction process, stable isotope internal standards are added to account for errors during sample preparation. Stable isotope dilution (SID) also accounts for any differences, such as ion suppression, that metabolites may experience during the mass spectrometry (MS) analysis9. After the extraction, derivatization with an electron capture (EC) reagent, pentafluorylbenzyl bromide (PFB) is employed to increase detection sensitivity10,11. Multiple reaction monitoring (MRM) is used to increase the selectivity of the MS analysis. Before MS analysis, lipids are separated using chiral normal phase high performance liquid chromatography (HPLC). The HPLC conditions are optimized to separate the enantiomers and various stereoisomers of the monitored lipids12. This specific LC-MS method monitors prostaglandins (PGs), isoprostanes (isoPs), hydroxyeicosatetraenoic acids (HETEs), hydroxyoctadecadienoic acids (HODEs), oxoeicosatetraenoic

  4. Bioactive Peptides from Muscle Sources: Meat and Fish

    Directory of Open Access Journals (Sweden)

    Catherine Stanton

    2011-08-01

    Full Text Available Bioactive peptides have been identified in a range of foods, including plant, milk and muscle, e.g., beef, chicken, pork and fish muscle proteins. Bioactive peptides from food proteins offer major potential for incorporation into functional foods and nutraceuticals. The aim of this paper is to present an outline of the bioactive peptides identified in the muscle protein of meat to date, with a focus on muscle protein from domestic animals and fish. The majority of research on bioactives from meat sources has focused on angiotensin-1-converting enzyme (ACE inhibitory and antioxidant peptides.

  5. StraPep: a structure database of bioactive peptides

    Science.gov (United States)

    Wang, Jian; Yin, Tailang; Xiao, Xuwen; He, Dan; Xue, Zhidong; Jiang, Xinnong; Wang, Yan

    2018-01-01

    Abstract Bioactive peptides, with a variety of biological activities and wide distribution in nature, have attracted great research interest in biological and medical fields, especially in pharmaceutical industry. The structural information of bioactive peptide is important for the development of peptide-based drugs. Many databases have been developed cataloguing bioactive peptides. However, to our knowledge, database dedicated to collect all the bioactive peptides with known structure is not available yet. Thus, we developed StraPep, a structure database of bioactive peptides. StraPep holds 3791 bioactive peptide structures, which belong to 1312 unique bioactive peptide sequences. About 905 out of 1312 (68%) bioactive peptides in StraPep contain disulfide bonds, which is significantly higher than that (21%) of PDB. Interestingly, 150 out of 616 (24%) bioactive peptides with three or more disulfide bonds form a structural motif known as cystine knot, which confers considerable structural stability on proteins and is an attractive scaffold for drug design. Detailed information of each peptide, including the experimental structure, the location of disulfide bonds, secondary structure, classification, post-translational modification and so on, has been provided. A wide range of user-friendly tools, such as browsing, sequence and structure-based searching and so on, has been incorporated into StraPep. We hope that this database will be helpful for the research community. Database URL: http://isyslab.info/StraPep PMID:29688386

  6. Fruit and cereal bioactives: sources, chemistry, and applications

    National Research Council Canada - National Science Library

    Tokusoglu, Ozlem; Hall, Clifford, III

    2011-01-01

    .... It provides detailed information on both beneficial bioactives such as phenolics, flavonoids, tocols, carotenoids, phytosterols, and avenanthramides and toxicant compounds including mycotoxins...

  7. Bioactivity of flours of seeds of leguminous crops Pisum sativum ...

    African Journals Online (AJOL)

    Bioactivity of flours of seeds of leguminous crops Pisum sativum, Phaseolus vulgaris and Glycine max used as botanical insecticides against Sitophilus oryzae Linnaeus (Coleoptera: Curculionidae) on sorghum grains.

  8. Lipids, lipid bilayers and vesicles as seen by neutrons

    International Nuclear Information System (INIS)

    Seto, Hideki

    2011-01-01

    Lipid molecules self-assemble into bilayers in water with their hydrocarbon chains facing inward due to their amphiphilic nature. The structural and dynamical properties of lipids and lipid bilayers have been studied by neutron scattering intensively. In this article, 3 topics are shown as typical examples. 1) a time-resolved small-angle neutron scattering on uni-lamellar vesicles composed of deuterated and protonated lipids to determine lipid kinetics, 2) small-angle neutron scattering to investigate spontaneous formation of nanopores on uni-lamellar vesicles, and 3) neutron spin echo study to determine bending modulus of lipid bilayers. (author)

  9. Endoplasmic Reticulum Lipid Flux Influences Enterocyte Nuclear Morphology and Lipid-dependent Transcriptional Responses.

    Science.gov (United States)

    Zeituni, Erin M; Wilson, Meredith H; Zheng, Xiaobin; Iglesias, Pablo A; Sepanski, Michael A; Siddiqi, Mahmud A; Anderson, Jennifer L; Zheng, Yixian; Farber, Steven A

    2016-11-04

    Responding to a high-fat meal requires an interplay between multiple digestive tissues, sympathetic response pathways, and the gut microbiome. The epithelial enterocytes of the intestine are responsible for absorbing dietary nutrients and preparing them for circulation to distal tissues, which requires significant changes in cellular activity, including both morphological and transcriptional responses. Following a high-fat meal, we observe morphological changes in the enterocytes of larval zebrafish, including elongation of mitochondria, formation and expansion of lipid droplets, and the rapid and transient ruffling of the nuclear periphery. Dietary and pharmacological manipulation of zebrafish larvae demonstrated that these subcellular changes are specific to triglyceride absorption. The transcriptional changes that occur simultaneously with these morphological changes were determined using RNA sequencing, revealing a cohort of up-regulated genes associated with lipid droplet formation and lipid transport via lipoprotein particles. Using a microsomal triglyceride transfer protein (MTP) inhibitor to block β-lipoprotein particle formation, we demonstrate that the transcriptional response to a high-fat meal is associated with the transfer of ER triglyceride to nascent β-lipoproteins, possibly through the activation of Creb3l3/cyclic AMP-responsive element-binding protein. These data suggest that a transient increase in ER lipids is the likely mediator of the initial physiological response of intestinal enterocytes to dietary lipid. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Endoplasmic Reticulum Lipid Flux Influences Enterocyte Nuclear Morphology and Lipid-dependent Transcriptional Responses*

    Science.gov (United States)

    Zeituni, Erin M.; Wilson, Meredith H.; Zheng, Xiaobin; Iglesias, Pablo A.; Sepanski, Michael A.; Siddiqi, Mahmud A.; Anderson, Jennifer L.; Zheng, Yixian; Farber, Steven A.

    2016-01-01

    Responding to a high-fat meal requires an interplay between multiple digestive tissues, sympathetic response pathways, and the gut microbiome. The epithelial enterocytes of the intestine are responsible for absorbing dietary nutrients and preparing them for circulation to distal tissues, which requires significant changes in cellular activity, including both morphological and transcriptional responses. Following a high-fat meal, we observe morphological changes in the enterocytes of larval zebrafish, including elongation of mitochondria, formation and expansion of lipid droplets, and the rapid and transient ruffling of the nuclear periphery. Dietary and pharmacological manipulation of zebrafish larvae demonstrated that these subcellular changes are specific to triglyceride absorption. The transcriptional changes that occur simultaneously with these morphological changes were determined using RNA sequencing, revealing a cohort of up-regulated genes associated with lipid droplet formation and lipid transport via lipoprotein particles. Using a microsomal triglyceride transfer protein (MTP) inhibitor to block β-lipoprotein particle formation, we demonstrate that the transcriptional response to a high-fat meal is associated with the transfer of ER triglyceride to nascent β-lipoproteins, possibly through the activation of Creb3l3/cyclic AMP-responsive element-binding protein. These data suggest that a transient increase in ER lipids is the likely mediator of the initial physiological response of intestinal enterocytes to dietary lipid. PMID:27655916

  11. Lipid management in ramadan.

    Science.gov (United States)

    Slim, Ines; Ach, Koussay; Chaieb, Larbi

    2015-05-01

    During Ramadan fast, Muslims must refrain from smoking, eating, drinking, having sexual activity, and consuming oral medications from sunrise to sunset. It has been previously shown that Ramadan fasting induces favourable changes on metabolic parameters, reduces oxidative stress and inflammation and promotes cardiovascular benefits. Although ill people are exempted from fasting, most patients with chronic diseases are keen on performing this Islamic-ritual. During recent years, Risk stratification and treatment adjustment during Ramadan are well known and structured in several guidelines for patients with diabetes mellitus. Data related to the effect of Ramadan fast on lipid profiles are less known and several controversies have been reported. Here, we focus on lipid profile and lipid management during Ramadan taking into account comorbidities and cardiovascular risk.

  12. Heart, lipids and hormones

    Directory of Open Access Journals (Sweden)

    Peter Wolf

    2017-05-01

    Full Text Available Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.

  13. Bioactive and inert dental glass-ceramics.

    Science.gov (United States)

    Montazerian, Maziar; Zanotto, Edgar Dutra

    2017-02-01

    The global market for dental materials is predicted to exceed 10 billion dollars by 2020. The main drivers for this growth are easing the workflow of dentists and increasing the comfort of patients. Therefore, remarkable research projects have been conducted and are currently underway to develop improved or new dental materials with enhanced properties or that can be processed using advanced technologies, such as CAD/CAM or 3D printing. Among these materials, zirconia, glass or polymer-infiltrated ceramics, and glass-ceramics (GCs) are of great importance. Dental glass-ceramics are highly attractive because they are easy to process and have outstanding esthetics, translucency, low thermal conductivity, high strength, chemical durability, biocompatibility, wear resistance, and hardness similar to that of natural teeth, and, in certain cases, these materials are bioactive. In this review article, we divide dental GCs into the following two groups: restorative and bioactive. Most restorative dental glass-ceramics (RDGCs) are inert and biocompatible and are used in the restoration and reconstruction of teeth. Bioactive dental glass-ceramics (BDGCs) display bone-bonding ability and stimulate positive biological reactions at the material/tissue interface. BDGCs are suggested for dentin hypersensitivity treatment, implant coating, bone regeneration and periodontal therapy. Throughout this paper, we elaborate on the history, processing, properties and applications of RDGCs and BDGCs. We also report on selected papers that address promising types of dental glass-ceramics. Finally, we include trends and guidance on relevant open issues and research possibilities. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 619-639, 2017. © 2016 Wiley Periodicals, Inc.

  14. Bioactive compounds: historical perspectives, opportunities, and challenges.

    Science.gov (United States)

    Patil, Bhimanagouda S; Jayaprakasha, G K; Chidambara Murthy, K N; Vikram, Amit

    2009-09-23

    Mom's conventional wisdom of eating fruits and vegetables to lead a healthy life has evolved with scientific, fact-finding research during the past four decades due to advances in science of "Foods for Health". Epidemiological and prospective studies have demonstrated the vital role of fruits, vegetables, and nuts in reducing the risk of cancer and cardiovascular diseases. In recent years, several meta-analyses strongly suggested that by adding one serving of fruits and vegetables to daily diet, the risk of cardiovascular diseases will be decreased up to 7%. The multidisciplinary and partnership efforts of agriculture and medical scientists across the globe stimulated interest in establishing certain interdisciplinary centers and institutes focusing on "Foods for Health". While the consumption of various healthy foods continues, several questions about toxicity, bioavailability, and food-drug interactions of bioactive compounds are yet to be fully understood on the basis of scientific evidence. Recent research on elucidation of the molecular mechanisms to understand the "proof of the concept" will provide the perfect answer when consumers are ready for a "consumer-to-farm" rather than the current "farm-to-consumer" approach. The multidisciplinary research and educational efforts will address the role of healthy foods to improve eye, brain, and heart health while reducing the risk of cancer. Through this connection, this review is an attempt to provide insight and historical perspectives on some of the bioactive compounds from the day of discovery to their current status. The bioactive compounds discussed in this review are flavonoids, carotenoids, curcumin, ascorbic acid, and citrus limonoids.

  15. LASER-INDUCED BIOACTIVITY IN DENTAL PORCELAIN MODIFIED BY BIOACTIVE GLASS

    Directory of Open Access Journals (Sweden)

    ANASTASIA BEKETOVA

    2012-12-01

    Full Text Available The aim of this study was to investigate the impact of laser-liquid-solid interaction method in the bioactivity of dental porcelain modified by bioactive glass. Forty sol-gel derived specimens were immersed in Dulbecco's Modified Eagle's Medium, 31 and 9 specimens of which were treated with Er:YAG and Nd:YAG laser respectively. Untreated specimens served as controls. Incubation of specimens followed. Bioactivity was evaluated, using Fourier Transform Infrared spectroscopy (FTIR, Scanning Electron Microscopy (SEM/Energy Dispersive Spectroscopy (EDS and Transmission Electron Microscopy (TEM. FTIR detected peaks associated with hydroxyapatite on 1 Nd:YAG- and 4 Er:YAG-treated specimens. SEM analysis revealed that Er:YAG-treated specimens were covered by granular hydroxyapatite layer, while Nd:YAG treated specimen presented growth of flake-like hydroxyapatite. TEM confirmed the results. The untreated controls presented delayed bioactivity. In conclusion, Nd:YAG and Er:YAG laser treatment of the material, under certain fluencies, accelerates hydroxyapatite formation. Nd:YAG laser treatment of specific parameters causes the precipitation of flake-like hydroxyapatite in nano-scale.

  16. In vitro bioactivity and mechanical properties of bioactive glass nanoparticles/polycaprolactone composites.

    Science.gov (United States)

    Ji, Lijun; Wang, Wenjun; Jin, Duo; Zhou, Songtao; Song, Xiaoli

    2015-01-01

    Nanoparticles of bioactive glass (NBG) with a diameter of 50-90 nm were synthesized using the Stöber method. NBG/PCL composites with different NBG contents (0 wt.%, 10 wt.%, 20 wt.%, 30 wt.% and 40 wt.%) were prepared by a melt blending and thermal injection moulding technique, and characterized with XRD, FTIR, and SEM to study the effect of NBG on the mechanical properties and in vitro bioactivity of the NBG/PCL composites. In spite of the high addition up to 40 wt.%, the NBG could be dispersed homogeneously in the PCL matrix. The elastic modulus of the NBG/PCL composites was improved remarkably from 198±13 MPa to 851±43 MPa, meanwhile the tensile strength was retained in the range of 19-21.5 MPa. The hydrophilic property and degradation behavior of the NBG/PCL composites were also improved with the addition of the NBG. Moreover, the composites with high NBG content showed outstanding in vitro bioactivity after being immersed in simulated body fluid, which could be attributed to the excellent bioactivity of the synthesized NBG. Copyright © 2014. Published by Elsevier B.V.

  17. Physicochemical properties and bioactivity of freeze-cast chitosan nanocomposite scaffolds reinforced with bioactive glass.

    Science.gov (United States)

    Pourhaghgouy, Masoud; Zamanian, Ali; Shahrezaee, Mostafa; Masouleh, Milad Pourbaghi

    2016-01-01

    Chitosan based nanocomposite scaffolds were prepared by freeze casting method through blending constant chitosan concentration with different portions of synthesized bioactive glass nanoparticles (BGNPs). Transmission Electron Microscopy (TEM) image showed that the particles size of bioactive glass (64SiO2.28CaO.8P2O5) prepared by sol-gel method was approximately less than 20 nm. Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray Diffraction (XRD) analysis showed proper interfacial bonding between BGNPs and chitosan polymers. Scanning Electron Microscopy (SEM) images depicted a unidirectional structure with homogenous distribution of BGNPs among chitosan matrix associated with the absence of pure chitosan scaffold's wall pores after addition of only 10 wt.% BGNPs. As the BGNP content increased from 0 to 50 wt.%, the compressive strength and compressive module values increased from 0.034 to 0.419 MPa and 0.41 to 10.77 MPa, respectively. Biodegradation study showed that increase in BGNP content leads to growth of weight loss amount. The in vitro biomineralization studies confirmed the bioactive nature of all nanocomposites. Amount of 30 wt.% BGNPs represented the best concentration for absorption capacity and bioactivity behaviors. Copyright © 2015. Published by Elsevier B.V.

  18. Influence of barium substitution on bioactivity, thermal and physico-mechanical properties of bioactive glass.

    Science.gov (United States)

    Arepalli, Sampath Kumar; Tripathi, Himanshu; Vyas, Vikash Kumar; Jain, Shubham; Suman, Shyam Kumar; Pyare, Ram; Singh, S P

    2015-04-01

    Barium with low concentration in the glasses acts as a muscle stimulant and is found in human teeth. We have made a primary study by substituting barium in the bioactive glass. The chemical composition containing (46.1-X) SiO2--24.3 Na2O-26.9 CaO-2.6 P2O5, where X=0, 0.4, 0.8, 1.2 and 1.6mol% of BaO was chosen and melted in an electric furnace at 1400±5°C. The glasses were characterized to determine their use in biomedical applications. The nucleation and crystallization regimes were determined by DTA and the controlled crystallization was carried out by suitable heat treatment. The crystalline phase formed was identified by using XRD technique. Bioactivity of these glasses was assessed by immersion in simulated body fluid (SBF) for various time periods. The formation of hydroxy carbonate apatite (HCA) layer was identified by FTIR spectrometry, scanning electron microscope (SEM) and XRD which showed the presence of HCA as the main phase in all tested bioactive glass samples. Flexural strength and densities of bioactive glasses have been measured and found to increase with increasing the barium content. The human blood compatibility of the samples was evaluated and found to be pertinent. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Bioactive glass coupling with natural polyphenols: Surface modification, bioactivity and anti-oxidant ability

    Science.gov (United States)

    Cazzola, Martina; Corazzari, Ingrid; Prenesti, Enrico; Bertone, Elisa; Vernè, Enrica; Ferraris, Sara

    2016-03-01

    Polyphenols are actually achieving an increasing interest due to their potential health benefits, such as antioxidant, anticancer, antibacterial and bone stimulation abilities. However their poor bioavailability and stability hamper an effective clinical application as therapeutic principles. The opportunity to couple these biomolecules with synthetic biomaterials, in order to obtain local delivery at the site of interest, improve their bioavailability and stability and combine their properties with the ones of the substrate, is a challenging opportunity for the biomedical research. A silica based bioactive glass, CEL2, has been successfully coupled with gallic acid and natural polyphenols extracted from red grape skins and green tea leaves. The effectiveness of grafting has been verified by means of XPS analyses and the Folin&Ciocalteu tests. In vitro bioactivity has been investigated by soaking in simulated body fluid (SBF). Surface modification after functionalization and early stage reactivity in SBF have been studied by means of zeta potential electrokinetic measurements in KCl and SBF. Finally the antioxidant properties of bare and modified bioactive glasses has been investigated by means of the evaluation of free radical scavenging activity by Electron Paramagnetic Resonance (EPR)/spin trapping technique after UV photolysis of H2O2 highlighting scavenging activity of the bioactive glass.

  20. Marine Nucleosides: Structure, Bioactivity, Synthesis and Biosynthesis

    Directory of Open Access Journals (Sweden)

    Ri-Ming Huang

    2014-12-01

    Full Text Available Nucleosides are glycosylamines that structurally form part of nucleotide molecules, the building block of DNA and RNA. Both nucleosides and nucleotides are vital components of all living cells and involved in several key biological processes. Some of these nucleosides have been obtained from a variety of marine resources. Because of the biological importance of these compounds, this review covers 68 marine originated nucleosides and their synthetic analogs published up to June 2014. The review will focus on the structures, bioactivities, synthesis and biosynthetic processes of these compounds.

  1. Nanostructuring Biomaterials with Specific Activities towards Digestive Enzymes for Controlled Gastrointestinal Absorption of Lipophilic Bioactive Molecules.

    Science.gov (United States)

    Joyce, Paul; Whitby, Catherine P; Prestidge, Clive A

    2016-11-01

    This review describes the development of novel lipid-based biomaterials that modulate fat digestion for the enhanced uptake of encapsulated lipophilic bioactive compounds (e.g. drugs and vitamins). Specific focus is directed towards analysing how key material characteristics affect the biological function of digestive lipases and manipulate lipolytic digestion. The mechanism of lipase action is a complex, interfacial process, whereby hydrolysis can be controlled by the ability for lipase to access and adsorb to the lipid-in-water interface. However, significant conjecture exists within the literature regarding parameters that influence the activities of digestive lipases. Important findings from recent investigations that strategically examined the interplay between the interfacial composition of the lipid microenvironment and lipolysis kinetics in simulated biophysical environments are presented. The correlation between lipolysis and the rate of solubilisation and absorption of lipophilic compounds in the gastrointestinal tract (GIT) is detailed. Greater insights into the mechanism of lipase action have provided a new approach for designing colloidal carriers that orally deliver poorly soluble compounds, directly impacting the pharmaceutical and food industries. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Composite bone cements loaded with a bioactive and ferrimagnetic glass-ceramic: Leaching, bioactivity and cytocompatibility

    International Nuclear Information System (INIS)

    Verné, Enrica; Bruno, Matteo; Miola, Marta; Maina, Giovanni; Bianco, Carlotta; Cochis, Andrea; Rimondini, Lia

    2015-01-01

    In this work, composite bone cements, based on a commercial polymethylmethacrylate matrix (Palamed®) loaded with ferrimagnetic bioactive glass-ceramic particles (SC45), were produced and characterized in vitro. The ferrimagnetic bioactive glass-ceramic belongs to the system SiO 2 –Na 2 O–CaO–P 2 O 5 –FeO–Fe 2 O 3 and contains magnetite (Fe 3 O 4 ) crystals into a residual amorphous bioactive phase. Three different formulations (containing 10, 15 and 20 wt.% of glass-ceramic particles respectively) have been investigated. These materials are intended to be applied as bone fillers for the hyperthermic treatment of bone tumors. The morphological, compositional, calorimetric and mechanical properties of each formulation have been already discussed in a previous paper. The in vitro properties of the composite bone cements described in the present paper are related to iron ion leaching test (by graphite furnace atomic absorption spectrometer), bioactivity (i.e. the ability to stimulate the formation of a hydroxyapatite – HAp – layer on their surface after soaking in simulated body fluid SBF) and cytocompatibility toward human osteosarcoma cells (ATCC CRL-1427, Mg63). Morphological and chemical characterizations by scanning electron microscopy and energy dispersion spectrometry have been performed on the composite samples after each test. The iron release was negligible and all the tested samples showed the growth of HAp on their surface after 28 days of immersion in a simulated body fluid (SBF). Cells showed good viability, morphology, adhesion, density and the ability to develop bridge-like structures on all investigated samples. A synergistic effect between bioactivity and cell mineralization was also evidenced. - Highlights: • An in vitro biological characterization was carried out on ferromagnetic and bioactive composite cements. • No release of iron was revealed in the physiological solution. • Bioactivity tests show hydroxyapatite precipitates

  3. Effect of nitrogen and fluorine on mechanical properties and bioactivity in two series of bioactive glasses.

    Science.gov (United States)

    Bachar, Ahmed; Mercier, Cyrille; Tricoteaux, Arnaud; Hampshire, Stuart; Leriche, Anne; Follet, Claudine

    2013-07-01

    Bioactive glasses are able to bond to bone through formation of carbonated hydroxyapatite in body fluids, and fluoride-releasing bioactive glasses are of interest for both orthopaedic and, in particular, dental applications for caries inhibition. However, because of their poor strength their use is restricted to non-load-bearing applications. In order to increase their mechanical properties, doping with nitrogen has been performed on two series of bioactive glasses: series (I) was a "bioglass" composition (without P2O5) within the quaternary system SiO2-Na2O-CaO-Si3N4 and series (II) was a simple substitution of CaF2 for CaO in series (I) glasses keeping the Na:Ca ratio constant. The objective of this work was to evaluate the effect of the variation in nitrogen and fluorine content on the properties of these glasses. The density, glass transition temperature, hardness and elastic modulus all increased linearly with nitrogen content which indicates that the incorporation of nitrogen stiffens the glass network because N is mainly in 3-fold coordination with Si atoms. Fluorine addition significantly decreases the thermal property values but the mechanical properties of these glasses remain unchanged with fluorine. The combination of both nitrogen and fluorine in oxyfluoronitride glasses gives better mechanical properties at much lower melting temperatures since fluorine reduces the melting point, allows higher solubility of nitrogen and does not affect the higher mechanical properties arising from incorporation of nitrogen. The characterization of these N and F substituted bioactive glasses using (29)Si MAS NMR has shown that the increase in rigidity of the glass network can be explained by the formation of SiO3N, SiO2N2 tetrahedra and Q(4) units with extra bridging anions at the expense of Q(3) units. Bioactivity of the glasses was investigated in vitro by examining apatite formation on the surface of glasses treated in acellular simulated body fluid (SBF) with ion

  4. Composite bone cements loaded with a bioactive and ferrimagnetic glass-ceramic: Leaching, bioactivity and cytocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Verné, Enrica, E-mail: enrica.verne@polito.it [Institute of Materials Physics and Engineering, Applied Science and Technology Department, Politecnico di Torino, C. so Duca degli Abruzzi 24, 10129 Torino (Italy); Bruno, Matteo [Institute of Materials Physics and Engineering, Applied Science and Technology Department, Politecnico di Torino, C. so Duca degli Abruzzi 24, 10129 Torino (Italy); Miola, Marta [Institute of Materials Physics and Engineering, Applied Science and Technology Department, Politecnico di Torino, C. so Duca degli Abruzzi 24, 10129 Torino (Italy); Department of Health Sciences, Università del Piemonte Orientale “Amedeo Avogadro”, Via Solaroli 17, 28100 Novara (Italy); Maina, Giovanni; Bianco, Carlotta [Traumatology Orthopedics and Occupational Medicine Dept., Università di Torino, Via G. Zuretti 29, 10126 Torino (Italy); Cochis, Andrea [Department of Health Sciences, Università del Piemonte Orientale “Amedeo Avogadro”, Via Solaroli 17, 28100 Novara (Italy); Rimondini, Lia [Department of Health Sciences, Università del Piemonte Orientale “Amedeo Avogadro”, Via Solaroli 17, 28100 Novara (Italy); Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali, Via G. Giusti, 9, 50121 Firenze (Italy)

    2015-08-01

    In this work, composite bone cements, based on a commercial polymethylmethacrylate matrix (Palamed®) loaded with ferrimagnetic bioactive glass-ceramic particles (SC45), were produced and characterized in vitro. The ferrimagnetic bioactive glass-ceramic belongs to the system SiO{sub 2}–Na{sub 2}O–CaO–P{sub 2}O{sub 5}–FeO–Fe{sub 2}O{sub 3} and contains magnetite (Fe{sub 3}O{sub 4}) crystals into a residual amorphous bioactive phase. Three different formulations (containing 10, 15 and 20 wt.% of glass-ceramic particles respectively) have been investigated. These materials are intended to be applied as bone fillers for the hyperthermic treatment of bone tumors. The morphological, compositional, calorimetric and mechanical properties of each formulation have been already discussed in a previous paper. The in vitro properties of the composite bone cements described in the present paper are related to iron ion leaching test (by graphite furnace atomic absorption spectrometer), bioactivity (i.e. the ability to stimulate the formation of a hydroxyapatite – HAp – layer on their surface after soaking in simulated body fluid SBF) and cytocompatibility toward human osteosarcoma cells (ATCC CRL-1427, Mg63). Morphological and chemical characterizations by scanning electron microscopy and energy dispersion spectrometry have been performed on the composite samples after each test. The iron release was negligible and all the tested samples showed the growth of HAp on their surface after 28 days of immersion in a simulated body fluid (SBF). Cells showed good viability, morphology, adhesion, density and the ability to develop bridge-like structures on all investigated samples. A synergistic effect between bioactivity and cell mineralization was also evidenced. - Highlights: • An in vitro biological characterization was carried out on ferromagnetic and bioactive composite cements. • No release of iron was revealed in the physiological solution. • Bioactivity tests

  5. Bioactive vegetable proteins and peptides in lipid-lowering: nutraceutical potential

    OpenAIRE

    Ruiz Ruiz, Jorge Carlos; Betancur Ancona, David Abram; Segura Campos, Maira Rubi

    2014-01-01

    As the last century saw a decline in the burden of nutritional deficiency and infectious disease, the global burden of chronic disease, cardiovascular disease (CVD) in particular, is increasing. CVD is the leading cause of death in the developed countries. Significant research efforts on the prevention and treatment of this disease have identified elevated plasma cholesterol as a primary risk factor for CVD. Although CVD progresses with hypercholesterolemia, it seems possibility to delay and ...

  6. The Role of ATP-Binding Cassette Transporters in Neuro-Inflammation: Relevance for Bioactive Lipids

    NARCIS (Netherlands)

    Kooij, G.; van Horssen, J.; Bandaru, V.V.R.; Haughey, N.J.; de Vries, H.E.

    2012-01-01

    ATP-binding cassette (ABC) transporters are highly expressed by brain endothelial cells that form the blood-brain barrier (BBB). These efflux pumps play an important role in maintaining brain homeostasis as they actively hinder the entry of unwanted blood-derived compounds into the central nervous

  7. The Role of ATP-Binding Cassette Transporters in Neuro-Inflammation: Relevance for Bioactive Lipids

    OpenAIRE

    Kooij, Gijs; van Horssen, Jack; Bandaru, Veera Venkata Ratnam; Haughey, Norman J.; de Vries, Helga E.

    2012-01-01

    ATP-binding cassette (ABC) transporters are highly expressed by brain endothelial cells that form the blood-brain barrier (BBB). These efflux pumps play an important role in maintaining brain homeostasis as they actively hinder the entry of unwanted blood-derived compounds into the central nervous system (CNS). Consequently, their high activity at the BBB has been a major hurdle for the treatment of several brain diseases, as they prevent numerous drugs to reach their site of action within th...

  8. Bioactive Lipidic Extracts from Octopus (Paraoctopus limaculatus: Antimutagenicity and Antiproliferative Studies

    Directory of Open Access Journals (Sweden)

    Carolina Moreno-Félix

    2013-01-01

    Full Text Available Fractions from an organic extract from fresh octopus (Paraoctopus limaculatus were studied for biological activities such as antimutagenic and antiproliferative properties using Salmonella tester strains TA98 and TA100 with metabolic activation (S9 and a cancer cell line (B-cell lymphoma, respectively. A chloroform extract obtained from octopus tentacles was sequentially fractionated using thin layer chromatography (TLC, and each fraction was tested for antimutagenic and antiproliferative activities. Organic extract reduced the number of revertants caused by aflatoxin B1 showing a dose-response type of relationship. Sequential TLC fractionation of the active extracts produced several antimutagenic and/or antiproliferative fractions. Based on the results obtained, the isolated fractions obtained from octopus contain compounds with chemoprotective properties that reduce the mutagenicity of AFB1 and proliferation of cancer cell lines.

  9. Fabrication and bioactivity behavior of HA/bioactive glass composites in the presence of calcium hexaboride

    Energy Technology Data Exchange (ETDEWEB)

    El-Bassyouni, Gehan T.; Beherei, Hanan H. [Biomaterials Dept., National Research Centre (NRC), Dokki, Cairo (Egypt); Mohamed, Khaled R., E-mail: kh_rezk1966@yahoo.com [Biomaterials Dept., National Research Centre (NRC), Dokki, Cairo (Egypt); Kenawy, Sayed H. [Ceramics Dept., National Research Centre (NRC), Dokki, Cairo (Egypt)

    2016-06-01

    In the current study, composites were prepared using both the synthesized nano-sized hydroxyapatite (HA), bioactive glass (BG) powders (obtained by the traditional melt-quenching route) together with the purchased nano-sized calcium hexaboride (CB) with different ratios and were fired at 1250 °C. The structure and composition of the solid reaction products were analyzed using X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy; scanning electron microscope (SEM) coupled with energy dispersive spectroscopy (EDS), transmission electron microscope (TEM) techniques and compressive strength. The mechanical testing was to designate the role of the CB in improving the mechanical property of the prepared composites. In vitro bioactivity of the prepared composites was assessed by soaking in the simulated body fluid (SBF) at 37 ± 0.5 °°C for 10 days. The effect of different ratios of the three components (CB, HA & BG) on the bioactivity properties was assessed to explore the possibility of enhancing such property to perform in vitro imitations of in vivo conditions in the future. It can be pointed out that the Si-HA content in the composition showed outstanding in vitro bioactivity than pure hydroxyapatite which could be attributed to the excellent bioactivity of the synthesized composites. - Highlights: • The prepared of nano-composites containing CB, HA and BG powders were achieved. • The addition of CB powder enhanced the compressive strength for all the composites. • The composites containing high BG and CB contents improved formation of bone-like apatite layer.

  10. Composite bone cements loaded with a bioactive and ferrimagnetic glass-ceramic: Leaching, bioactivity and cytocompatibility.

    Science.gov (United States)

    Verné, Enrica; Bruno, Matteo; Miola, Marta; Maina, Giovanni; Bianco, Carlotta; Cochis, Andrea; Rimondini, Lia

    2015-08-01

    In this work, composite bone cements, based on a commercial polymethylmethacrylate matrix (Palamed®) loaded with ferrimagnetic bioactive glass-ceramic particles (SC45), were produced and characterized in vitro. The ferrimagnetic bioactive glass-ceramic belongs to the system SiO2-Na2O-CaO-P2O5-FeO-Fe2O3 and contains magnetite (Fe3O4) crystals into a residual amorphous bioactive phase. Three different formulations (containing 10, 15 and 20 wt.% of glass-ceramic particles respectively) have been investigated. These materials are intended to be applied as bone fillers for the hyperthermic treatment of bone tumors. The morphological, compositional, calorimetric and mechanical properties of each formulation have been already discussed in a previous paper. The in vitro properties of the composite bone cements described in the present paper are related to iron ion leaching test (by graphite furnace atomic absorption spectrometer), bioactivity (i.e. the ability to stimulate the formation of a hydroxyapatite - HAp - layer on their surface after soaking in simulated body fluid SBF) and cytocompatibility toward human osteosarcoma cells (ATCC CRL-1427, Mg63). Morphological and chemical characterizations by scanning electron microscopy and energy dispersion spectrometry have been performed on the composite samples after each test. The iron release was negligible and all the tested samples showed the growth of HAp on their surface after 28 days of immersion in a simulated body fluid (SBF). Cells showed good viability, morphology, adhesion, density and the ability to develop bridge-like structures on all investigated samples. A synergistic effect between bioactivity and cell mineralization was also evidenced. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Fabrication and bioactivity behavior of HA/bioactive glass composites in the presence of calcium hexaboride

    International Nuclear Information System (INIS)

    El-Bassyouni, Gehan T.; Beherei, Hanan H.; Mohamed, Khaled R.; Kenawy, Sayed H.

    2016-01-01

    In the current study, composites were prepared using both the synthesized nano-sized hydroxyapatite (HA), bioactive glass (BG) powders (obtained by the traditional melt-quenching route) together with the purchased nano-sized calcium hexaboride (CB) with different ratios and were fired at 1250 °C. The structure and composition of the solid reaction products were analyzed using X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy; scanning electron microscope (SEM) coupled with energy dispersive spectroscopy (EDS), transmission electron microscope (TEM) techniques and compressive strength. The mechanical testing was to designate the role of the CB in improving the mechanical property of the prepared composites. In vitro bioactivity of the prepared composites was assessed by soaking in the simulated body fluid (SBF) at 37 ± 0.5 °°C for 10 days. The effect of different ratios of the three components (CB, HA & BG) on the bioactivity properties was assessed to explore the possibility of enhancing such property to perform in vitro imitations of in vivo conditions in the future. It can be pointed out that the Si-HA content in the composition showed outstanding in vitro bioactivity than pure hydroxyapatite which could be attributed to the excellent bioactivity of the synthesized composites. - Highlights: • The prepared of nano-composites containing CB, HA and BG powders were achieved. • The addition of CB powder enhanced the compressive strength for all the composites. • The composites containing high BG and CB contents improved formation of bone-like apatite layer.

  12. An Efficient Glycoblotting-Based Analysis of Oxidized Lipids in Liposomes and a Lipoprotein.

    Science.gov (United States)

    Furukawa, Takayuki; Hinou, Hiroshi; Takeda, Seiji; Chiba, Hitoshi; Nishimura, Shin-Ichiro; Hui, Shu-Ping

    2017-10-05

    Although widely occurring lipid oxidation, which is triggered by reactive oxygen species (ROS), produces a variety of oxidized lipids, practical methods to efficiently analyze oxidized lipids remain elusive. Herein, it is shown that the glycoblotting platform can be used to analyze oxidized lipids. Analysis is based on the principle that lipid aldehydes, one of the oxidized lipid species, can be captured selectively, enriched, and detected. Moreover, 3-methyl-1-p-tolyltriazene (MTT) methylates phosphoric and carboxylic acids, and this MTT-mediated methylation is, in combination with conventional tandem mass spectrometry (MS/MS) analysis, an effective method for the structural analysis of oxidized lipids. By using three classes of standards, liposomes, and a lipoprotein, it is demonstrated that glycoblotting represents a powerful approach for focused lipidomics, even in complex macromolecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Affinity of four polar neurotransmitters for lipid bilayer membranes

    DEFF Research Database (Denmark)

    Wang, Chunhua; Ye, Fengbin; Valardez, Gustavo F.

    2011-01-01

    . The simulations suggest that this attraction mainly relies on electrostatic interactions of the amino group of the neurotransmitter and the lipid phosphate. We conclude that moderate attraction to lipid membranes occurs for some polar neurotransmitters and hence that one premise for a theory of bilayer-mediated......Weak interactions of neurotransmitters and the lipid matrix in the synaptic membrane have been hypothesized to play a role in synaptic transmission of nerve signals, particularly with respect to receptor desensitization (Cantor, R. S. Biochemistry 2003, 42, 11891). The strength of such interactions......, however, was not measured, and this is an obvious impediment for further evaluation and understanding of a possible role for desensitization. We have used dialysis equilibrium to directly measure the net affinity of selected neurotransmitters for lipid membranes and analyzed this affinity data...

  14. Bioactive Polymeric Materials for Tissue Repair

    Directory of Open Access Journals (Sweden)

    Diane R. Bienek

    2017-01-01

    Full Text Available Bioactive polymeric materials based on calcium phosphates have tremendous appeal for hard tissue repair because of their well-documented biocompatibility. Amorphous calcium phosphate (ACP-based ones additionally protect against unwanted demineralization and actively support regeneration of hard tissue minerals. Our group has been investigating the structure/composition/property relationships of ACP polymeric composites for the last two decades. Here, we present ACP’s dispersion in a polymer matrix and the fine-tuning of the resin affects the physicochemical, mechanical, and biological properties of ACP polymeric composites. These studies illustrate how the filler/resin interface and monomer/polymer molecular structure affect the material’s critical properties, such as ion release and mechanical strength. We also present evidence of the remineralization efficacy of ACP composites when exposed to accelerated acidic challenges representative of oral environment conditions. The utility of ACP has recently been extended to include airbrushing as a platform technology for fabrication of nanofiber scaffolds. These studies, focused on assessing the feasibility of incorporating ACP into various polymer fibers, also included the release kinetics of bioactive calcium and phosphate ions from nanofibers and evaluate the biorelevance of the polymeric ACP fiber networks. We also discuss the potential for future integration of the existing ACP scaffolds into therapeutic delivery systems used in the precision medicine field.

  15. Angiogenesis stimulated by novel nanoscale bioactive glasses

    International Nuclear Information System (INIS)

    Mao, Cong; Chen, Xiaofeng; Miao, Guohou; Lin, Cai

    2015-01-01

    The ability of biomaterials to induce rapid vascular formation is critical in tissue regeneration. Combining recombinant angiogenic growth factors with bioengineered constructs have proven to be difficult due to several issues, including the instability of recombinant proteins, the need for sustained delivery and the dosage of factors. New formulations of bioactive glass, 58S nanosized bioactive glass (58S-NBG), have been reported to enhance wound healing in animal models better than the first generation of 45S5 Bioglass. Therefore, we investigated the effects of extracts of 58S-NBG and 80S-NBG on cultures of human umbilical vein endothelial cells (HUVECs). Cell viability was assessed by MTS assay. In vitro angiogenesis was measured using an ECM gel tube formation assay, and levels of mRNAs for five angiogenic related genes were measured by qRT-PCR. Extracts of 58S-NBG and 80S-NBG stimulated the proliferation of HUVECs, accelerated cell migration, up-regulated expression of the vascular endothelial growth factor, basic fibroblast growth factor, their receptors, and endothelial nitric oxide synthase, resulting in enhanced tube formation in vitro. The enhanced angiogenic response correlated with increased levels of Ca and Si in the extracts of 58S-NBG and 80S-NBG. The ability of 58S-NBG and 80S-NBG to stimulate angiogenesis in vitro provides alternative approaches for stimulating neovascularization of tissue-engineered constructs. (paper)

  16. Bioactive endophytes warrant intensified exploration and conservation.

    Science.gov (United States)

    Smith, Stephen A; Tank, David C; Boulanger, Lori-Ann; Bascom-Slack, Carol A; Eisenman, Kaury; Kingery, David; Babbs, Beatrice; Fenn, Kathleen; Greene, Joshua S; Hann, Bradley D; Keehner, Jocelyn; Kelley-Swift, Elizabeth G; Kembaiyan, Vivek; Lee, Sun Jin; Li, Puyao; Light, David Y; Lin, Emily H; Ma, Cong; Moore, Emily; Schorn, Michelle A; Vekhter, Daniel; Nunez, Percy V; Strobel, Gary A; Donoghue, Michael J; Strobel, Scott A

    2008-08-25

    A key argument in favor of conserving biodiversity is that as yet undiscovered biodiversity will yield products of great use to humans. However, the link between undiscovered biodiversity and useful products is largely conjectural. Here we provide direct evidence from bioassays of endophytes isolated from tropical plants and bioinformatic analyses that novel biology will indeed yield novel chemistry of potential value. We isolated and cultured 135 endophytic fungi and bacteria from plants collected in Peru. nrDNAs were compared to samples deposited in GenBank to ascertain the genetic novelty of cultured specimens. Ten endophytes were found to be as much as 15-30% different than any sequence in GenBank. Phylogenetic trees, using the most similar sequences in GenBank, were constructed for each endophyte to measure phylogenetic distance. Assays were also conducted on each cultured endophyte to record bioactivity, of which 65 were found to be bioactive. The novelty of our contribution is that we have combined bioinformatic analyses that document the diversity found in environmental samples with culturing and bioassays. These results highlight the hidden hyperdiversity of endophytic fungi and the urgent need to explore and conserve hidden microbial diversity. This study also showcases how undergraduate students can obtain data of great scientific significance.

  17. Bioactive endophytes warrant intensified exploration and conservation.

    Directory of Open Access Journals (Sweden)

    Stephen A Smith

    2008-08-01

    Full Text Available A key argument in favor of conserving biodiversity is that as yet undiscovered biodiversity will yield products of great use to humans. However, the link between undiscovered biodiversity and useful products is largely conjectural. Here we provide direct evidence from bioassays of endophytes isolated from tropical plants and bioinformatic analyses that novel biology will indeed yield novel chemistry of potential value.We isolated and cultured 135 endophytic fungi and bacteria from plants collected in Peru. nrDNAs were compared to samples deposited in GenBank to ascertain the genetic novelty of cultured specimens. Ten endophytes were found to be as much as 15-30% different than any sequence in GenBank. Phylogenetic trees, using the most similar sequences in GenBank, were constructed for each endophyte to measure phylogenetic distance. Assays were also conducted on each cultured endophyte to record bioactivity, of which 65 were found to be bioactive.The novelty of our contribution is that we have combined bioinformatic analyses that document the diversity found in environmental samples with culturing and bioassays. These results highlight the hidden hyperdiversity of endophytic fungi and the urgent need to explore and conserve hidden microbial diversity. This study also showcases how undergraduate students can obtain data of great scientific significance.

  18. Recent advances on bioactivities of black rice.

    Science.gov (United States)

    Dias, Aécio L de S; Pachikian, Barbara; Larondelle, Yvan; Quetin-Leclercq, Joëlle

    2017-11-01

    Black rice has been consumed for centuries in Asian countries such as China, Korea or Japan. Nowadays, extracts and derivatives are considered as beneficial functional foods because of their high content in several bioactive molecules such as anthocyanins, other phenolics and terpenoids. The purpose of this review is to summarize and discuss recent developments on black rice bioactivities. Some sterols and triterpenoids with potential anticancer properties already tested in vitro and in vivo have been isolated and identified from bran extracts of black rice. Protection against osteoporosis has been suggested for the first time for black rice extracts. Because of its antioxidant and anti-inflammatory properties, black rice also protects liver and kidney from injuries. One clinical study reported the interest of black rice in case of alcohol withdrawal. Several advances have been recently achieved on the understanding of the potential biological effects of black rice and its derivatives. They further confirm that black rice should be considered as a promising source of health-promoting functional foods targeting a large set of noninfectious diseases. However, more clinical studies are needed to support the findings highlighted in this review.

  19. Bioactive Peptides in Animal Food Products

    Directory of Open Access Journals (Sweden)

    Marzia Albenzio

    2017-05-01

    Full Text Available Proteins of animal origin represent physiologically active components in the human diet; they exert a direct action or constitute a substrate for enzymatic hydrolysis upon food processing and consumption. Bioactive peptides may descend from the hydrolysis by digestive enzymes, enzymes endogenous to raw food materials, and enzymes from microorganisms added during food processing. Milk proteins have different polymorphisms for each dairy species that influence the amount and the biochemical characteristics (e.g., amino acid chain, phosphorylation, and glycosylation of the protein. Milk from other species alternative to cow has been exploited for their role in children with cow milk allergy and in some infant pathologies, such as epilepsy, by monitoring the immune status. Different mechanisms concur for bioactive peptides generation from meat and meat products, and their functionality and application as functional ingredients have proven effects on consumer health. Animal food proteins are currently the main source of a range of biologically-active peptides which have gained special interest because they may also influence numerous physiological responses in the organism. The addition of probiotics to animal food products represent a strategy for the increase of molecules with health and functional properties.

  20. Preparation of radiolabeled bioactive asbestos fibers

    Energy Technology Data Exchange (ETDEWEB)

    Tewson, T J; Francsechini, M P; Scheule, R K; Holian, A [Texas Univ., Houston, TX (USA). Health Science Center

    1991-01-01

    We have developed an efficient procedure to radiolabel asbestos fibers while retaining the bioactivity of the fibers. The fibers are labeled with {sup 68}Ge. The {sup 68}Ge decays into {sup 68}Ga, which then can be detected by its characteristic positron emission. Both chrysotile and crocidolite asbestos, a serpentine and an amphibole, respectively, were radiolabeled successfully. Mild reaction conditions and short reaction times were found under which {similar to}90% of the added {sup 68}Ge and {sup 68}Ga bound to the fibers. The radiolabel was retained even after washing the fibers extensively with physiologic buffers. The effects of the labeling on the bioactivity of the fibers were evaluated in an in vitro assay using guinea pig alveolar macrophages as a target cell. Labeled chrysotile fibers were found to retain >95% of their ability to stimulate these cells. The labeling procedure described in this study should be useful in preparing labeled fibers to investigate both in vitro and in vivo phenomena. (author).

  1. Lipid storage myopathies.

    Science.gov (United States)

    Bruno, Claudio; Dimauro, Salvatore

    2008-10-01

    The aim of this review is to provide an update on disorders of lipid metabolism affecting skeletal muscle exclusively or predominantly and to summarize recent clinical, genetic, and therapeutic studies in this field. Over the past 5 years, new clinical phenotypes and genetic loci have been described, unusual pathogenic mechanisms have been elucidated, and novel pharmacological approaches have been developed. At least one genetic defect responsible for the myopathic form of CoQ10 deficiency has been identified, causing a disorder that is allelic with the late-onset riboflavine-responsive form of multiple acyl-coenzyme A dehydrogenation deficiency. Novel mechanisms involved in the lipolytic breakdown of cellular lipid depots have been described and have led to the identification of genes and mutations responsible for multisystemic neutral lipid storage disorders, characterized by accumulation of triglyceride in multiple tissues, including muscle. Defects in lipid metabolism can affect either the mitochondrial transport and oxidation of exogenous fatty acid or the catabolism of endogenous triglycerides. These disorders impair energy production and almost invariably involve skeletal muscle, causing progressive myopathy with muscle weakness, or recurrent acute episodes of rhabdomyolysis triggered by exercise, fasting, or infections. Clinical and genetic characterization of these disorders has important implications both for accurate diagnostic approach and for development of therapeutic strategies.

  2. Lipids in airway secretions

    International Nuclear Information System (INIS)

    Bhaskar, K.R.; DeFeudis O'Sullivan, D.; Opaskar-Hincman, H.; Reid, L.M.

    1987-01-01

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO 2 , (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors 14 C acetate and 14 C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway. (author)

  3. Exogenous lipid pneumonia

    International Nuclear Information System (INIS)

    Bernasconi, A.; Gavelli, G.; Zompatori, M.; Galleri, C.; Zanasi, A.; Fabbri, M.; Bazzocchi, F.

    1988-01-01

    Exogenous lipid pneumonia (ELP) is caused by the aspiration of animal, vegetal or, more often, mineral oils. Even though it may also be acute, ELP is most frequently a chronic disease, affecting people with predisposing factors, such as neuromuscular disorders, structural abnormalities and so on; very often exogenous lipid pneumonia is found in tracheotomized patients. The pathology of lipid pneumonia is a chronic inflammatory process evolving in foreign-body-like reaction, and eventually in ''end-stage lung'' condition. Clinically, most patients are asymptomatic; few cases only present with cough, dyspnea and chest pain. Eight cases of ELP, studied over the past 3 years, are described in this paper. All the patients were examined by chest radiographs and standard tomograms; 3 patients underwent CT. X-ray features were mono/bilateral consolidation of the lower zones, with air bronchogram and variable reduction in volume. CT density was not specific for fat tissue. In all cases the diagnosis was confirmed at biopsy. In 5 patients, followed for at least one year, clinical-radiological features showed no change. Thus, complications of ELP (especially malignant evolution) could be excluded. The authors conclude that lipid pneumonia must be considered in differential diagnosis of patients with history of usage of oils and compatible X-ray findings. The usefulness of an accurate follow-up is stressed

  4. Lipid Therapy for Intoxications

    NARCIS (Netherlands)

    Robben, Joris Henricus; Dijkman, Marieke Annet

    This review discusses the use of intravenous lipid emulsion (ILE) in the treatment of intoxications with lipophilic agents in veterinary medicine. Despite growing scientific evidence that ILE has merit in the treatment of certain poisonings, there is still uncertainty on the optimal composition of

  5. Lipid Therapy for Intoxications

    NARCIS (Netherlands)

    Robben, Joris Henricus; Dijkman, Marieke Annet

    2017-01-01

    This review discusses the use of intravenous lipid emulsion (ILE) in the treatment of intoxications with lipophilic agents in veterinary medicine. Despite growing scientific evidence that ILE has merit in the treatment of certain poisonings, there is still uncertainty on the optimal composition of

  6. Bioavailability of bioactive food compounds: a challenging journey to bioefficacy

    Science.gov (United States)

    Rein, Maarit J.; Renouf, Mathieu; Cruz‐Hernandez, Cristina; Actis‐Goretta, Lucas; Thakkar, Sagar K.; da Silva Pinto, Marcia

    2013-01-01

    Bioavailability is a key step in ensuring bioefficacy of bioactive food compounds or oral drugs. Bioavailability is a complex process involving several different stages: liberation, absorption, distribution, metabolism and elimination phases (LADME). Bioactive food compounds, whether derived from various plant or animal sources, need to be bioavailable in order to exert any beneficial effects. Through a better understanding of the digestive fate of bioactive food compounds we can impact the promotion of health and improvement of performance. Many varying factors affect bioavailability, such as bioaccessibility, food matrix effect, transporters, molecular structures and metabolizing enzymes. Bioefficacy may be improved through enhanced bioavailability. Therefore, several technologies have been developed to improve the bioavailability of xenobiotics, including structural modifications, nanotechnology and colloidal systems. Due to the complex nature of food bioactive compounds and also to the different mechanisms of absorption of hydrophilic and lipophilic bioactive compounds, unravelling the bioavailability of food constituents is challenging. Among the food sources discussed during this review, coffee, tea, citrus fruit and fish oil were included as sources of food bioactive compounds (e.g. (poly)phenols and polyunsaturated fatty acids (PUFAs)) since they are examples of important ingredients for the food industry. Although there are many studies reporting on bioavailability and bioefficacy of these bioactive food components, understanding their interactions, metabolism and mechanism of action still requires extensive work. This review focuses on some of the major factors affecting the bioavailability of the aforementioned bioactive food compounds. PMID:22897361

  7. Bioactivity and chemical ecology of some intertidal animals

    Digital Repository Service at National Institute of Oceanography (India)

    Parulekar, A.H.; Shirwaikar, P.

    stream_size 7 stream_content_type text/plain stream_name Bioactive_Com_Mar_Org_1991_29.pdf.txt stream_source_info Bioactive_Com_Mar_Org_1991_29.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 ...

  8. Abrasive wear behaviour of bio-active glass ceramics containing ...

    Indian Academy of Sciences (India)

    In this study, abrasive wear behaviour of bio-active glass ceramic materials produced with two different processes is studied. Hot pressing process and conventional casting and controlled crystallization process were used to produce bio-active ceramics. Fracture toughness of studied material was calculated by fracture ...

  9. calcium sulphate hemihydrate and bioactive glass composites for ...

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science; Volume 41; Issue 2. In vitro bioactivity evaluation of α -calcium sulphate hemihydrate and bioactive glass composites for their potential use in bone regeneration. YANYAN ZHENG CHENGDONG XIONG DUJUAN ZHANG LIFANG ZHANG. Volume 41 Issue 2 April 2018 Article ID ...

  10. Bioactive Peptides in Milk Products. | Tirelli | Journal of Food ...

    African Journals Online (AJOL)

    Some peptides produced in vitro or in vivo by enzymatic hydrolysis of caseins and whey protein can affect some biological functions of the body and therefore they are called bioactive peptides. In this paper the physiological significance of bioactive peptides is reviewed and the analytical methods for their purification and ...

  11. Nutrient reference values for bioactives: new approaches needed?

    DEFF Research Database (Denmark)

    Biesalski, Hans Konrad; Erdman Jr., John W.; Hathcock, John

    2013-01-01

    Nutrients can be classified as either "essential" or "non-essential," the latter are also termed bioactive substances. Whereas the absence of essential nutrients from the diet results in overt deficiency often times with moderate to severe physiological decrements, the absence of bioactive substa...

  12. The ecological dynamics and trajectories of bioactive compounds in ...

    African Journals Online (AJOL)

    Result revealed seven bioactive compounds with anthraquinone totally absent from all the species in the four locations. The seven bioactive compounds were apparently more in the leaves than other parts of the plants. Among the four locations alkaloid, triterpene, glycoside, carbohydrate, flavonoid and tannin were high in ...

  13. Big, Fat World of Lipids

    Science.gov (United States)

    ... offered a more quantitative and systematic approach to lipids research. Much of the effort has been led by a research consortium called LIPID MAPS. With funding from the National Institutes of ...

  14. Amphotericin B Lipid Complex Injection

    Science.gov (United States)

    Amphotericin B lipid complex injection is used to treat serious, possibly life-threatening fungal infections in people who did ... respond or are unable to tolerate conventional amphotericin B therapy. Amphotericin B lipid complex injection is in ...

  15. Lipid status in phyisiological non-complicated pregnancy

    Directory of Open Access Journals (Sweden)

    Ardalić Daniela

    2016-01-01

    Full Text Available Specifically altered lipid profile and physiological hyperlipidemia during pregnancy are considered essential for the normal course of pregnancy and fetal development. This specific alteration of the lipid profile raises the questions about potential proaterogenic effect of these altered lipid parameters during pregnancy and its influence on the development of cardiovascular disease in women later in life. Research topic was also the association of altered lipid profile during pregnancy with the development of complications in pregnancy, especially gestational diabetes, hypertension and preeclampsia. Through the mediation of cholesterol ester transfer protein (CETP, the activity of which grows in mid-gestation, there are exchanges of the triglycerides between VLDL and LDL or HDL particle, which leads to increased accumulation of triglycerides in these particles, causes them to become smaller and denser with much greater atherogenic potential. These changes in lipid profile point out that a large number of pregnancies increase risk of development of cardiovascular diseases later in life. In order to optimize the predictive capacity of the lipid profile during pregnancy, it is recommended to determine the indexes of lipid.

  16. Synthesis and Structural Characterization of Bioactive PHA and γ-PGA Oligomers for Potential Applications as a Delivery System

    Directory of Open Access Journals (Sweden)

    Iwona Kwiecień

    2016-04-01

    Full Text Available The (transesterification reaction of bacterial biopolymers with a selected bioactive compound with a hydroxyl group was applied as a convenient method for obtaining conjugates of such compound. Tyrosol, a naturally occurring phenolic compound, was selected as a model of a bioactive compound with a hydroxyl group. Selected biodegradable polyester and polyamide, poly(3-hydroxybutyrate-co-4-hydroxybutyrate (P(3HB-co-4HB and poly-γ-glutamic acid (γ-PGA, respectively, were used. The (transesterification reactions were carried out in melt mediated by 4-toluenesulfonic acid monohydrate. The structures of (transesterification products were established at the molecular level with the aid of ESI-MS2 (electrospray ionization tandem mass spectrometry and/or 1H NMR (nuclear magnetic resonance techniques. Performed analyses confirmed that the developed method leads to the formation of conjugates in which bioactive compounds are covalently bonded to biopolymer chains. The amount of covalently bonded bioactive compounds in the resulting conjugates depends on the type of biopolymers applied in synthesis.

  17. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  18. The Evaluation and Utilization of Marine-derived Bioactive Compounds with Anti-obesity Effect.

    Science.gov (United States)

    Jin, Qiu; Yu, Huahua; Li, Pengcheng

    2018-01-01

    Obesity is a global epidemic throughout the world. There is thus increasing interest in searching for natural bioactive compounds with anti-obesity effect. A number of marine compounds have been regarded as potential sources of bioactive compounds and are associated with an anti-obesity effect. Marine-derived compounds with anti-obesity effect and their current applications, methods and indicators for the evaluation of anti-obesity activity are summarized in this review. in order to make contributions to the development of marine-derived functional food against obesity. In this review, an overview of marine-derived compounds with anti-obesity effect, including marine polysaccharides, marine lipid, marine peptides, marine carotenoids is intensively made with an emphasis on their efficacy and mechanism of action. Meanwhile, methods and indicators for the evaluation of anti-obesity activity are discussed. We summarize these methods into three categories: in vitro assay (including adsorption experiments and enzyme inhibitory assay), cell line study, animal experiments and clinical experiments. In addition, a brief introduction of the current applications of marine bioactive compounds with anti-obesity activity is discussed. Marine environment is a rich source of both biological and chemical diversity. In the past decades, numerous novel compounds with anti-obesity activity have been obtained from marine organisms, and many of them have been applied to industrial production such as functional foods and pharmaceuticals. Further studies are needed to explore the above-mentioned facts. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Centesimal composition and bioactive compounds in fruits of buriti collected in Pará

    Directory of Open Access Journals (Sweden)

    Luciana Ribeiro Trajano Manhães

    2011-12-01

    Full Text Available The link between diet and the incidence of chronic and degenerative diseases has already been established. The foods that play a role in preventing and/or treating these diseases are called functional foods. Buriti can be highlighted amongst these foods since it is an excellent source of vegetable oil, which is rich in β-carotene and oleic acid. This research evaluated the potential of the pulp of this fruit as a functional food focusing on its incorporation to the diet. Buriti pulp presented 62.93% moisture, 8.25% total carbohydrates, and 2.10% protein. The lipid fraction corresponded to 13.85%, and oleic acid was the main fatty acid. It also contained 0.94% total mineral content. Based on the results obtained, it can be said that the pulp of buriti may contain bioactive compounds with functional activities, but further research is needed to assess such potential.

  20. Bioactivity-guided fractionation of the triglyceride-lowering component and in vivo and in vitro evaluation of hypolipidemic effects of Calyx seu Fructus Physalis.

    Science.gov (United States)

    Yang, Yihui; Piao, Xianmei; Zhang, Mingyu; Wang, Xiaodan; Xu, Bing; Zhu, Jiuxin; Fang, Zhiwei; Hou, Yunlong; Lu, Yanjie; Yang, Baofeng

    2012-03-14

    In folklore, some people take the decoction of Calyx seu Fructus Physalis (CSFP) for lowering blood lipids. The present study is designed to evaluate the lipid-lowering activities of CSFP, and search for its pharmacodynamical material. CSFP was extracted by water and 75% ethanol, respectively. The extracts of CSFP for reducing serum lipid levels were evaluated on mouse model of hyperlipidemia. The optimized extract was subjected to the bioactivity-guided fractionation in which the liquid-liquid extraction, collumn chromatography, the in vivo and in vitro models of hyperlipidemia were utilized. The structure of active component was determined by ¹³C-NMR and ¹H-NMR. The 75% ethanol extract of CSFP decreased the serum total cholesterol (TC) and triglyceride (TG) levels in mouse model of hyperlipidemia. Followed a separation process for the 75% ethanol extract of CSFP, the fraction B was proved to be an active fraction for lowering lipid in vivo and in vitro experiments, which could significantly decrease the serum TC and TG levels in mouse model of hyperlipidemia, and remarkably decrease the increase of TG in primary mouse hepatocytes induced by high glucose and the increase of TG in HepG2 cells induced by oleic acid. The fraction B2, isolated from B on bioactivity-guided fractionation, could significantly decrease TG level in HepG2 cells. One compound with the highest content in B2 was isolated and determined as luteolin-7-O-beta-D-glucopyranoside by NMR spectra. It could significantly reduce the TG level in HepG2 cells, and inhibited the accumulation of lipids by oil red O stain. Our results demonstrated that the 75% ethanol extract of CSFP could improve in vitro and in vivo lipid accumulation. Luteolin-7-O-beta-D-glucopyranoside might be a leading pharmacodynamical material of CSFP for lowering lipids.

  1. The lipid fraction of human milk initiates adipocyte differentiation in 3T3-L1 cells.

    Science.gov (United States)

    Fujisawa, Yasuko; Yamaguchi, Rie; Nagata, Eiko; Satake, Eiichiro; Sano, Shinichiro; Matsushita, Rie; Kitsuta, Kazunobu; Nakashima, Shinichi; Nakanishi, Toshiki; Nakagawa, Yuichi; Ogata, Tsutomu

    2013-09-01

    The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood. We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined. We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail. These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Bioactivity of different enriched phenolic extracts of wild fruits from Northeastern Portugal: a comparative study.

    Science.gov (United States)

    Guimarães, Rafaela; Barros, Lillian; Calhelha, Ricardo C; Carvalho, Ana Maria; Queiroz, Maria João R P; Ferreira, Isabel C F R

    2014-03-01

    Arbutus unedo, Prunus spinosa, Rosa micrantha and Rosa canina are good sources of phenolic compounds, including anthocyanins. These compounds have potent antioxidant properties, which have been related to anticancer activity. Herein, the in vitro antioxidant and antitumor properties of enriched phenolic extracts (non-anthocyanin phenolic compounds enriched extract- PE and anthocyanins enriched extract- AE) of the mentioned wild fruits were evaluated and compared. PE gave higher bioactive properties than the corresponding AE. It was observed a high capacity of A. unedo phenolic extract to inhibit lipid peroxidation in animal brain homogenates (EC50 = 7.21 μg/mL), as also a high antitumor potential against NCI-H460 human cell line (non-small lung cancer; GI50 = 37.68 μg/mL), which could be related to the presence of galloyl derivatives (exclusively found in this species). The bioactivity of the studied wild fruits proved to be more related to the phenolic compounds profile than to the amounts present in each extract, and could be considered in the design of new formulations of dietary supplements or functional foods.

  3. Chemical composition, fatty acid profile and bioactive compounds of guava seeds (Psidium guajava L.

    Directory of Open Access Journals (Sweden)

    Ana Maria Athayde Uchôa-thomaz

    2014-09-01

    Full Text Available This study aimed to characterize the chemical composition, determine the fatty acid profile, and quantify the bioactive compounds present in guava seed powder (Psidium guajava L.. The powder resulted from seeds obtained from guava pulp processing. The agro-industrial seeds from red guava cv. paluma were used, and they were donated by a frozen pulp fruit manufacturer. They contain varying amounts of macronutrients and micronutrients, with a high content of total dietary fiber (63.94 g/100g, protein (11.19 g/100g, iron (13.8 mg/100g, zinc (3.31 mg/100g, and reduced calorie content (182 kcal/100g. Their lipid profile showed a predominance of unsaturated fatty acids (87.06%, especially linoleic acid (n6 and oleic acid (n9. The powder obtained contained significant amounts of bioactive compounds such as ascorbic acid (87.44 mg/100g, total carotenoids (1.25 mg/100 g and insoluble dietary fiber (63.55 g/100g. With regard to their microbiological quality, the samples were found suitable for consumption. Based on these results, it can be concluded that the powder produced has favorable attributes for industrial use, and that use of these seeds would be a viable alternative to prevent various diseases and malnutrition in our country and to reduce the environmental impact of agricultural waste.

  4. Unraveling the Complex Relationship Triad between Lipids, Obesity, and Inflammation

    Directory of Open Access Journals (Sweden)

    Shahida A. Khan

    2014-01-01

    Full Text Available Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. Majorly the thromboxanes, prostaglandins, leukotrienes, lipoxins, and so forth form the group of lipid mediators influencing inflammation. Of special mention are the omega-6 and omega-3 fatty acids that regulate inflammatory mediators of interest in hepatocytes and adipocytes via the cyclooxygenase and lipoxygenase pathways. They also exhibit profound effects on eicosanoid production. The inflammatory cyclooxygenase pathway arising from arachidonic acid is a critical step in the progression of inflammatory responses. New oxygenated products of omega-3 metabolism, namely, resolvins and protectins, behave as endogenous mediators exhibiting powerful anti-inflammatory and immune-regulatory actions via the peroxisome proliferator-activated receptors (PPARs and G protein coupled receptors (GPCRs. In this review we attempt to discuss the complex pathways and links between obesity and inflammation particularly in relation to different lipid mediators.

  5. The effect of rosemary (Rosmarinus officinalis L.) extract on the oxidative stability of lipids in cow and soy milk enriched with fish oil.

    Science.gov (United States)

    Qiu, Xujian; Jacobsen, Charlotte; Sørensen, Ann-Dorit Moltke

    2018-10-15

    Lipid oxidation of fish oil enriched cow milk and soy milk supplemented with rosemary extract stored at 2 °C was studied. Both peroxide value and volatile secondary lipid oxidation products were determined to monitor the progress of lipid oxidation. Rosemary extract inhibited lipid oxidation in fish oil enriched cow milk. In contrast, soy milk samples having much higher unsaturated fatty acid content showed higher lipid oxidation stability compared to cow milk. Reduction in the content of chlorogenic acid during storage suggested that this compound may contribute to the lipid oxidation stability of fish oil enriched soy milk product. Total carnosic acid and carnosol concentration declined much faster in soy milk than in cow milk. It is suggested from the results that food components could have significant impact on the fate of bioactive antioxidant compounds in a specific food product during storage. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Activation of c-Src and Fyn kinases by protein tyrosine phosphatase RPTPalpha is substrate-specific and compatible with lipid raft localization

    DEFF Research Database (Denmark)

    Vacaresse, Nathalie; Møller, Bente; Danielsen, Erik Michael

    2008-01-01

    and the lipid raft scaffolding protein Cbp/PAG. A significant fraction of RPTPa is present in lipid rafts, where its targets Fyn and Cbp/PAG reside, and growth factor-mediated SFK activation within this compartment is strictly dependent on RPTPa. Forced concentration of RPTPa into lipid rafts is compatible...

  7. Bioactive and Antibacterial Coatings Based on Zein/Bioactive Glass Composites by Electrophoretic Deposition

    Directory of Open Access Journals (Sweden)

    Nima Meyer

    2018-01-01

    Full Text Available This study investigated the electrophoretic deposition (EPD of the natural polymer zein combined with bioactive glass (BG particles. Through the deposition of various BG compositions, namely 45S5 BG and Cu-doped BG, this work sought to demonstrate the ability of the films to potentiate the formation of hydroxyapatite (HA in contact with simulated body fluid (SBF. Following incubation in SBF, the physical and chemical surface properties of the EPD films were evaluated using different characterization techniques. The formation of HA at the surface of the coatings following immersion in SBF was confirmed using Fourier transform infrared spectroscopy (FTIR. The results demonstrated HA formation in all coatings after seven days of immersion in SBF. Coating morphology and degradation of the zein films were characterized using environmental scanning electron microscopy (ESEM. The results confirmed EPD as a very convenient room temperature technique for production of ion releasing, bioactive, and antibacterial coatings for potential application in orthopedics.

  8. Bioactive Triterpenes from the Fungus Piptoporus betulinus

    Directory of Open Access Journals (Sweden)

    Zeyad Alresly

    2016-01-01

    Full Text Available Phytochemical investigation of the ethyl acetate extract of the fruiting bodies from the basidiomycete Piptoporus betulinus led to the isolation of a new bioactive lanostane triterpene identified as 3 b -acetoxy-16-hydroxy-24-oxo-5α-lanosta-8- ene-21-oic acid (1. In addition, ten known triterpenes, polyporenic acid A (5, polyporenic acid C (4, three derivatives of polyporenic acid A (8, 10, 11, betulinic acid (3, betulin (2, ergosterol peroxide (6, 9,11-dehydroergosterol peroxide (7, and fomefficinic acid (9, were also isolated from the fungus. All isolated compounds were tested for antimicrobial activity against some Gram-positive and Gram-negative bacteria as well as against a fungal strain. The new triterpene and some of the other compounds showed antimicrobial activity against Gram-positive bacteria.

  9. Bioactive glass coatings for orthopedic metallic implants

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Esteban, Sonia; Saiz, Eduardo; Fujino, Sigheru; Oku, Takeo; Suganuma, Katsuaki; Tomsia, Antoni P.

    2003-06-30

    The objective of this work is to develop bioactive glass coatings for metallic orthopedic implants. A new family of glasses in the SiO2-Na2O-K2O-CaO-MgO-P2O5 system has been synthesized and characterized. The glass properties (thermal expansion, softening and transformation temperatures, density and hardness) are in line with the predictions of established empirical models. The optimized firing conditions to fabricate coatings on Ti-based and Co-Cr alloys have been determined and related to the glass properties and the interfacial reactions. Excellent adhesion to alloys has been achieved through the formation of 100-200 nm thick interfacial layers (Ti5Si3 on Ti-based alloys and CrOx on Co-Cr). Finally, glass coatings, approximately 100 mu m thick, have been fabricated onto commercial Ti alloy-based dental implants.

  10. Bioactivity and Functionality of Bonghwa Sweetfish

    International Nuclear Information System (INIS)

    Kim, Jae Hun; Lee, Ju Woon; Choi, Jong Il; Song, Beom Seok; Yoon, Yo Han; Sung, Nak Yun; Jeong, Pil Mun

    2010-04-01

    - Smoked sweetfish had higher contents of calories, carbohydrate, protein, fat sodium, and calcium than unsmoked sweetfish - DHA and EPA which are omega-3 fatty acid and have therapeutic effects on arthritis and high blood pressure - Proteins and peptide from sweetfish had various bioactivities such as antioxidation, hypertensive, especially for antiinflammatory, and whitening effects. However no anticancer effect was observed - The proteins and peptide suppressed nitric oxide and cytokines (a-TNF, IL-6, IL-1 beta), and prostaglandin (PGE2) productions, and mRNA related iNOS and cyclooxygenase (COX-2), which are related to inflammation - The proteins and peptide prevented tyrosinase formation, which is related formation of melanin, and also showed preventive effects of melanin synthesis, antioxidation and anti-aging effects. Thus, the proteins and peptides from sweetfish may be useful source for cosmetics

  11. Bioactive Compounds Found in Brazilian Cerrado Fruits.

    Science.gov (United States)

    Bailão, Elisa Flávia Luiz Cardoso; Devilla, Ivano Alessandro; da Conceição, Edemilson Cardoso; Borges, Leonardo Luiz

    2015-10-09

    Functional foods include any natural product that presents health-promoting effects, thereby reducing the risk of chronic diseases. Cerrado fruits are considered a source of bioactive substances, mainly phenolic compounds, making them important functional foods. Despite this, the losses of natural vegetation in the Cerrado are progressive. Hence, the knowledge propagation about the importance of the species found in Cerrado could contribute to the preservation of this biome. This review provides information about Cerrado fruits and highlights the structures and pharmacologic potential of functional compounds found in these fruits. Compounds detected in Caryocar brasiliense Camb. (pequi), Dipteryx alata Vog. (baru), Eugenia dysenterica DC. (cagaita), Eugenia uniflora L. (pitanga), Genipa americana L. (jenipapo), Hancornia speciosa Gomes (mangaba), Mauritia flexuosa L.f. (buriti), Myrciaria cauliflora (DC) Berg (jabuticaba), Psidium guajava L. (goiaba), Psidium spp. (araçá), Solanum lycocarpum St. Hill (lobeira), Spondias mombin L. (cajá), Annona crassiflora Mart. (araticum), among others are reported here.

  12. Bioactivity and Functionality of Bonghwa Sweetfish

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Hun; Lee, Ju Woon; Choi, Jong Il; Song, Beom Seok; Yoon, Yo Han; Sung, Nak Yun; Jeong, Pil Mun

    2010-04-15

    - Smoked sweetfish had higher contents of calories, carbohydrate, protein, fat sodium, and calcium than unsmoked sweetfish - DHA and EPA which are omega-3 fatty acid and have therapeutic effects on arthritis and high blood pressure - Proteins and peptide from sweetfish had various bioactivities such as antioxidation, hypertensive, especially for antiinflammatory, and whitening effects. However no anticancer effect was observed - The proteins and peptide suppressed nitric oxide and cytokines (a-TNF, IL-6, IL-1 beta), and prostaglandin (PGE2) productions, and mRNA related iNOS and cyclooxygenase (COX-2), which are related to inflammation - The proteins and peptide prevented tyrosinase formation, which is related formation of melanin, and also showed preventive effects of melanin synthesis, antioxidation and anti-aging effects. Thus, the proteins and peptides from sweetfish may be useful source for cosmetics

  13. Bioactive Compounds Found in Brazilian Cerrado Fruits

    Directory of Open Access Journals (Sweden)

    Elisa Flávia Luiz Cardoso Bailão

    2015-10-01

    Full Text Available Functional foods include any natural product that presents health-promoting effects, thereby reducing the risk of chronic diseases. Cerrado fruits are considered a source of bioactive substances, mainly phenolic compounds, making them important functional foods. Despite this, the losses of natural vegetation in the Cerrado are progressive. Hence, the knowledge propagation about the importance of the species found in Cerrado could contribute to the preservation of this biome. This review provides information about Cerrado fruits and highlights the structures and pharmacologic potential of functional compounds found in these fruits. Compounds detected in Caryocar brasiliense Camb. (pequi, Dipteryx alata Vog. (baru, Eugenia dysenterica DC. (cagaita, Eugenia uniflora L. (pitanga, Genipa americana L. (jenipapo, Hancornia speciosa Gomes (mangaba, Mauritia flexuosa L.f. (buriti, Myrciaria cauliflora (DC Berg (jabuticaba, Psidium guajava L. (goiaba, Psidium spp. (araçá, Solanum lycocarpum St. Hill (lobeira, Spondias mombin L. (cajá, Annona crassiflora Mart. (araticum, among others are reported here.

  14. Characterization,Mechanical, and In Vitro Bioactivity Properties of Hydroxyapatite/Bioactive Glass Composite

    Directory of Open Access Journals (Sweden)

    Israa Kahatan Sabree

    2016-12-01

    Full Text Available Bioactive ceramic materials can help bone reparation and regeneration by offering support to bone growth. Biological hydroxyapatite powder was prepared by burning animal bone followed by studying the mechanical properties of hydroxyapatite (HA/ (20wt.%, and 40wt.% of binary bioactive glass (70% SiO2- 30% CaO in order to evaluate the influence of composition on the compressive strength and hardness. HA-composite material exhibited increasing density, microhardness, and compressive strength with increasing amount of glass addition. X-ray diffraction after sintering at 1200°C showed no alter of HA to secondary phases while the hydroxyapatite/ bioactive glass composites contained a HA phase and different amounts of wollastonite phase, depending on the amount of bioglass added. In vitro tests, the samples were soaked in simulated body fluid (SBF for ten days in order to evaluate the change in compression strength, weight loss, and pH. The HA composite reinforced with 40 wt % bioglass showed highest compression strength, and lowest weight loss

  15. Polar lipids of Burkholderia pseudomallei induce different host immune responses.

    Directory of Open Access Journals (Sweden)

    Mercedes Gonzalez-Juarrero

    Full Text Available Melioidosis is a disease in tropical and subtropical regions of the world that is caused by Burkholderia pseudomallei. In endemic regions the disease occurs primarily in humans and goats. In the present study, we used the goat as a model to dissect the polar lipids of B. pseudomallei to identify lipid molecules that could be used for adjuvants/vaccines or as diagnostic tools. We showed that the lipidome of B. pseudomallei and its fractions contain several polar lipids with the capacity to elicit different immune responses in goats, namely rhamnolipids and ornithine lipids which induced IFN-γ, whereas phospholipids and an undefined polar lipid induced strong IL-10 secretion in CD4(+ T cells. Autologous T cells co-cultured with caprine dendritic cells (cDCs and polar lipids of B. pseudomallei proliferated and up-regulated the expression of CD25 (IL-2 receptor molecules. Furthermore, we demonstrated that polar lipids were able to up-regulate CD1w2 antigen expression in cDCs derived from peripheral blood monocytes. Interestingly, the same polar lipids had only little effect on the expression of MHC class II DR antigens in the same caprine dendritic cells. Finally, antibody blocking of the CD1w2 molecules on cDCs resulted in decreased expression for IFN-γ by CD4(+ T cells. Altogether, these results showed that polar lipids of B. pseudomallei are recognized by the caprine immune system and that their recognition is primarily mediated by the CD1 antigen cluster.

  16. Polar Lipids of Burkholderia pseudomallei Induce Different Host Immune Responses

    Science.gov (United States)

    Gonzalez-Juarrero, Mercedes; Mima, Naoko; Trunck, Lily A.; Schweizer, Herbert P.; Bowen, Richard A.; Dascher, Kyle; Mwangi, Waithaka; Eckstein, Torsten M.

    2013-01-01

    Melioidosis is a disease in tropical and subtropical regions of the world that is caused by Burkholderia pseudomallei. In endemic regions the disease occurs primarily in humans and goats. In the present study, we used the goat as a model to dissect the polar lipids of B. pseudomallei to identify lipid molecules that could be used for adjuvants/vaccines or as diagnostic tools. We showed that the lipidome of B. pseudomallei and its fractions contain several polar lipids with the capacity to elicit different immune responses in goats, namely rhamnolipids and ornithine lipids which induced IFN-γ, whereas phospholipids and an undefined polar lipid induced strong IL-10 secretion in CD4+ T cells. Autologous T cells co-cultured with caprine dendritic cells (cDCs) and polar lipids of B. pseudomallei proliferated and up-regulated the expression of CD25 (IL-2 receptor) molecules. Furthermore, we demonstrated that polar lipids were able to up-regulate CD1w2 antigen expression in cDCs derived from peripheral blood monocytes. Interestingly, the same polar lipids had only little effect on the expression of MHC class II DR antigens in the same caprine dendritic cells. Finally, antibody blocking of the CD1w2 molecules on cDCs resulted in decreased expression for IFN-γ by CD4+ T cells. Altogether, these results showed that polar lipids of B. pseudomallei are recognized by the caprine immune system and that their recognition is primarily mediated by the CD1 antigen cluster. PMID:24260378

  17. Analysis of lipid raft molecules in the living brain slices.

    Science.gov (United States)

    Kotani, Norihiro; Nakano, Takanari; Ida, Yui; Ito, Rina; Hashizume, Miki; Yamaguchi, Arisa; Seo, Makoto; Araki, Tomoyuki; Hojo, Yasushi; Honke, Koichi; Murakoshi, Takayuki

    2017-08-24

    Neuronal plasma membrane has been thought to retain a lot of lipid raft components which play important roles in the neural function. Although the biochemical analyses of lipid raft using brain tissues have been extensively carried out in the past 20 years, many of their experimental conditions do not coincide with those of standard neuroscience researches such as neurophysiology and neuropharmacology. Hence, the physiological methods for lipid raft analysis that can be compatible with general neuroscience have been required. Herein, we developed a system to physiologically analyze ganglioside GM1-enriched lipid rafts in brain tissues using the "Enzyme-Mediated Activation of Radical Sources (EMARS)" method that we reported (Kotani N. et al. Proc. Natl. Acad. Sci. U S A 105, 7405-7409 (2008)). The EMARS method was applied to acute brain slices prepared from mouse brains in aCSF solution using the EMARS probe, HRP-conjugated cholera toxin subunit B, which recognizes ganglioside GM1. The membrane molecules present in the GM1-enriched lipid rafts were then labeled with fluorescein under the physiological condition. The fluorescein-tagged lipid raft molecules called "EMARS products" distributed differentially among various parts of the brain. On the other hand, appreciable differences were not detected among segments along the longitudinal axis of the hippocampus. We further developed a device to label the lipid raft molecules in acute hippocampal slices under two different physiological conditions to detect dynamics of the lipid raft molecules during neural excitation. Using this device, several cell membrane molecules including Thy1, known as a lipid raft resident molecule in neurons, were confirmed by the EMARS method in living hippocampal slices. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Involvement of glycosphingolipid-enriched lipid rafts in inflammatory responses.

    Science.gov (United States)

    Iwabuchi, Kazuhisa

    2015-01-01

    Glycosphingolipids (GSLs) are membrane components consisting of hydrophobic ceramide and hydrophilic sugar moieties. GSLs cluster with cholesterol in cell membranes to form GSL-enriched lipid rafts. Biochemical analyses have demonstrated that GSL-enriched lipid rafts contain several kinds of transducer molecules, including Src family kinases. Among the GSLs, lactosylceramide (LacCer, CDw17) can bind to various microorganisms, is highly expressed on the plasma membranes of human phagocytes, and forms lipid rafts containing the Src family tyrosine kinase Lyn. LacCer-enriched lipid rafts mediate immunological and inflammatory reactions, including superoxide generation, chemotaxis, and non-opsonic phagocytosis. Therefore, LacCer-enriched membrane microdomains are thought to function as pattern recognition receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs) expressed on microorganisms. LacCer also serves as a signal transduction molecule for functions mediated by CD11b/CD18-integrin (αM/β2-integrin, CR3, Mac-1), as well as being associated with several key cellular processes. LacCer recruits PCKα/ε and phospholipase A2 to stimulate PECAM-1 expression in human monocytes and their adhesion to endothelial cells, as well as regulating β1-integrin clustering and endocytosis on cell surfaces. This review describes the organizational and inflammation-related functions of LacCer-enriched lipid rafts.

  19. CREBH Regulates Systemic Glucose and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Yoshimi Nakagawa

    2018-05-01

    Full Text Available The cyclic adenosine monophosphate (cAMP-responsive element-binding protein H (CREBH, encoded by CREB3L3 is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins related to lipoprotein lipase (LPL activation. CREBH in the small intestine reduces cholesterol transporter gene Npc1l1 and suppresses cholesterol absorption from diet. A deficiency of CREBH in mice leads to severe hypertriglyceridemia, fatty liver, and atherosclerosis. CREBH, in synergy with peroxisome proliferator-activated receptor α (PPARα, has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis including glucose and lipid metabolism. CREBH binds to and functions as a co-activator for both PPARα and liver X receptor alpha (LXRα in regulating gene expression of lipid metabolism. Therefore, CREBH has a crucial role in glucose and lipid metabolism in the liver and small intestine.

  20. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  1. In vitro bioactivity of 17alpha-estradiol.

    Science.gov (United States)

    Sievernich, André; Wildt, Ludwig; Lichtenberg-Fraté, Hella

    2004-12-01

    A miniaturised short-term in vitro assay based on the activation of the human estrogen receptor alpha and genetically modified yeast (Saccharomyces cerevisiae) cells was performed to explore the capacity of this system to monitor the bioactivity of estrogenic compounds, particularly 17alpha- and 17beta-estradiol. Together with the human estrogen receptor (hER)-alpha plasmid, the reporter plasmid containing a yeast-optimised version of the green fluorescent protein (yEGFP) linked to three repeats of the cis-acting estrogen hormone-responsive element (ERE) were expressed in a strain being deleted in the pleiotropic drug resistance transporters Pdr5, Snq2 and Yor1, known to facilitate efflux of organic compounds including steroids and chemotherapeutics. Agonists that bind to hER in vitro trigger estrogen receptor-mediated transcriptional activation of the GFP reporter gene monitored by fluorescence emission at 535 nm. The sensitivity of the assay was tested with various 17alpha- and 17beta-estradiol concentrations, yielding a detection limit of 5 pg/ml (0.018 nM) for the agonist 17beta-E2 in solvent and in human charcoal-stripped serum using a S. cerevisiae pdr5, snq2 and yor1 mutant strain. For 17alpha-estradiol only, at approximately 1500 pg/ml a similar fluorescence response compared to 100 pg/ml 17beta-E2 was observed implicating a much weaker potency of this stereoisomer. The specificity of the system was tested by expression of a truncated hER lacking the ligand-binding domain E and by administration of the androgen, 4-androsten 3,17 dione. Both controls did not yield an increase in fluorescence emission. This fluorescence emission assay enables detection of estrogenic biological activity induced by direct agonists, such as 17beta-E2 at concentrations similar to those found in human sera or by estrogen-like chemicals.

  2. Seipin is required for converting nascent to mature lipid droplets

    DEFF Research Database (Denmark)

    Wang, Huajin; Becuwe, Michel; Housden, Benjamin E

    2016-01-01

    How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation-the conversion of small, nascent LDs to larger, mature LDs. Seipin...... leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent...

  3. In vitro bioactivity and antimicrobial tuning of bioactive glass nanoparticles added with neem (Azadirachta indica) leaf powder.

    Science.gov (United States)

    Prabhu, M; Ruby Priscilla, S; Kavitha, K; Manivasakan, P; Rajendran, V; Kulandaivelu, P

    2014-01-01

    Silica and phosphate based bioactive glass nanoparticles (58SiO2-33CaO-9P2O5) with doping of neem (Azadirachta indica) leaf powder and silver nanoparticles were prepared and characterised. Bioactive glass nanoparticles were produced using sol-gel technique. In vitro bioactivity of the prepared samples was investigated using simulated body fluid. X-ray diffraction (XRD) pattern of prepared glass particles reveals amorphous phase and spherical morphology with a particle size of less than 50 nm. When compared to neem doped glass, better bioactivity was attained in silver doped glass through formation of hydroxyapatite layer on the surface, which was confirmed through XRD, Fourier transform infrared (FTIR), and scanning electron microscopy (SEM) analysis. However, neem leaf powder doped bioactive glass nanoparticles show good antimicrobial activity against Staphylococcus aureus and Escherichia coli and less bioactivity compared with silver doped glass particles. In addition, the biocompatibility of the prepared nanocomposites reveals better results for neem doped and silver doped g