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Mar. Drugs, Volume 13, Issue 12 (December 2015), Pages 7055-7475

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Research

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Open AccessArticle Mycosporine-Like Amino Acids Promote Wound Healing through Focal Adhesion Kinase (FAK) and Mitogen-Activated Protein Kinases (MAP Kinases) Signaling Pathway in Keratinocytes
Mar. Drugs 2015, 13(12), 7055-7066; doi:10.3390/md13127056
Received: 20 August 2015 / Revised: 10 November 2015 / Accepted: 18 November 2015 / Published: 26 November 2015
Cited by 5 | PDF Full-text (2177 KB) | HTML Full-text | XML Full-text
Abstract
Mycosporine-like amino acids (MAAs) are secondary metabolites found in diverse marine, freshwater, and terrestrial organisms. Evidence suggests that MAAs have several beneficial effects on skin homeostasis such as protection against UV radiation and reactive oxygen species (ROS). In addition, MAAs are also involved
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Mycosporine-like amino acids (MAAs) are secondary metabolites found in diverse marine, freshwater, and terrestrial organisms. Evidence suggests that MAAs have several beneficial effects on skin homeostasis such as protection against UV radiation and reactive oxygen species (ROS). In addition, MAAs are also involved in the modulation of skin fibroblasts proliferation. However, the regulatory function of MAAs on wound repair in human skin is not yet clearly elucidated. To investigate the roles of MAAs on the wound healing process in human keratinocytes, three MAAs, Shinorine (SH), Mycosporine-glycine (M-Gly), and Porphyra (P334) were purified from Chlamydomonas hedlyei and Porphyra yezoensis. We found that SH, M-Gly, and P334 have significant effects on the wound healing process in human keratinocytes and these effects were mediated by activation of focal adhesion kinases (FAK), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinases (JNK). These results suggest that MAAs accelerate wound repair by activating the FAK-MAPK signaling pathways. This study also indicates that MAAs can act as a new wound healing agent and further suggests that MAAs might be a novel biomaterial for wound healing therapies. Full article
(This article belongs to the Special Issue Marine Secondary Metabolites)
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Open AccessArticle Effects of Organic and Inorganic Nitrogen on the Growth and Production of Domoic Acid by Pseudo-nitzschia multiseries and P. australis (Bacillariophyceae) in Culture
Mar. Drugs 2015, 13(12), 7067-7086; doi:10.3390/md13127055
Received: 27 June 2015 / Revised: 10 November 2015 / Accepted: 12 November 2015 / Published: 26 November 2015
Cited by 6 | PDF Full-text (1180 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Over the last century, human activities have altered the global nitrogen cycle, and anthropogenic inputs of both inorganic and organic nitrogen species have increased around the world, causing significant changes to the functioning of aquatic ecosystems. The increasing frequency of Pseudo-nitzschia spp. in
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Over the last century, human activities have altered the global nitrogen cycle, and anthropogenic inputs of both inorganic and organic nitrogen species have increased around the world, causing significant changes to the functioning of aquatic ecosystems. The increasing frequency of Pseudo-nitzschia spp. in estuarine and coastal waters reinforces the need to understand better the environmental control of its growth and domoic acid (DA) production. Here, we document Pseudo-nitzschia spp. growth and toxicity on a large set of inorganic and organic nitrogen (nitrate, ammonium, urea, glutamate, glutamine, arginine and taurine). Our study focused on two species isolated from European coastal waters: P. multiseries CCL70 and P. australis PNC1. The nitrogen sources induced broad differences between the two species with respect to growth rate, biomass and cellular DA, but no specific variation could be attributed to any of the inorganic or organic nitrogen substrates. Enrichment with ammonium resulted in an enhanced growth rate and cell yield, whereas glutamate did not support the growth of P. multiseries. Arginine, glutamine and taurine enabled good growth of P. australis, but without toxin production. The highest DA content was produced when P. multiseries grew with urea and P. australis grew with glutamate. For both species, growth rate was not correlated with DA content but more toxin was produced when the nitrogen source could not sustain a high biomass. A significant negative correlation was found between cell biomass and DA content in P. australis. This study shows that Pseudo-nitzschia can readily utilize organic nitrogen in the form of amino acids, and confirms that both inorganic and organic nitrogen affect growth and DA production. Our results contribute to our understanding of the ecophysiology of Pseudo-nitzschia spp. and may help to predict toxic events in the natural environment. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
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Open AccessArticle Cytotoxic Effects of Tropodithietic Acid on Mammalian Clonal Cell Lines of Neuronal and Glial Origin
Mar. Drugs 2015, 13(12), 7113-7123; doi:10.3390/md13127058
Received: 8 October 2015 / Revised: 7 November 2015 / Accepted: 18 November 2015 / Published: 27 November 2015
Cited by 3 | PDF Full-text (4370 KB) | HTML Full-text | XML Full-text
Abstract
The marine metabolite tropodithietic acid (TDA), produced by several Roseobacter clade bacteria, is known for its broad antimicrobial activity. TDA is of interest not only as a probiotic in aquaculture, but also because it might be of use as an antibacterial agent in
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The marine metabolite tropodithietic acid (TDA), produced by several Roseobacter clade bacteria, is known for its broad antimicrobial activity. TDA is of interest not only as a probiotic in aquaculture, but also because it might be of use as an antibacterial agent in non-marine or non-aquatic environments, and thus the potentially cytotoxic influences on eukaryotic cells need to be evaluated. The present study was undertaken to investigate its effects on cells of the mammalian nervous system, i.e., neuronal N2a cells and OLN-93 cells as model systems for nerve cells and glia. The data show that in both cell lines TDA exerted morphological changes and cytotoxic effects at a concentration of 0.3–0.5 µg/mL (1.4–2.4 µM). Furthermore, TDA caused a breakdown of the mitochondrial membrane potential, the activation of extracellular signal-regulated kinases ERK1/2, and the induction of the small heat shock protein HSP32/HO-1, which is considered as a sensor of oxidative stress. The cytotoxic effects were accompanied by an increase in intracellular Ca2+-levels, the disturbance of the microtubule network, and the reorganization of the microfilament system. Hence, mammalian cells are a sensitive target for the action of TDA and react by the activation of a stress response resulting in cell death. Full article
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Open AccessArticle Influence of Temperature on Growth and Production of Pectenotoxin-2 by a Monoclonal Culture of Dinophysis caudata
Mar. Drugs 2015, 13(12), 7124-7137; doi:10.3390/md13127061
Received: 5 June 2015 / Revised: 1 November 2015 / Accepted: 20 November 2015 / Published: 3 December 2015
Cited by 1 | PDF Full-text (1806 KB) | HTML Full-text | XML Full-text
Abstract
The effects of temperature on growth and production of Lipophilic Toxins (LT) by a monoclonal culture of Dinophysis caudata was studied. The cell density of D. caudata increased significantly with increasing temperature, and was the highest under 27, 30, and 32.5 °C. Temperature
[...] Read more.
The effects of temperature on growth and production of Lipophilic Toxins (LT) by a monoclonal culture of Dinophysis caudata was studied. The cell density of D. caudata increased significantly with increasing temperature, and was the highest under 27, 30, and 32.5 °C. Temperature affected the average specific growth rate (µ) during the exponential growth phase (EG), which increased from 15 °C to 30 °C, and then decreased at 32.5 °C. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed that this strain of D. caudata produced only pectenotoxin-2 (PTX-2) whose concentration increased significantly with incubation period, except at 32.5 °C. It was significantly different between temperatures ≤18 °C, ≥21 °C, and 32.5 °C. The cellular toxin production (CTP, pg·cell−1·day−1) showed variation with growth phase and temperature, except at 32.5 °C. The average net toxin production (Rtox) was not affected by temperature. During EG, the average specific toxin production rate (µtox) increased significantly with increase in temperature, reaching a peak of 0.66 ± 0.01 day−1 at 30 °C, and then decreased. Over the entire growth span, µtox was significantly correlated to µ, and this correlation was most significant at 27 and 30 °C. During EG, µtox was affected by both temperature and growth. This study shows that temperature affects growth and toxin production of this strain of D. caudata during EG. In addition, a positive correlation was found between toxin production and growth. Full article
(This article belongs to the Special Issue Okadaic Acid and Dinophysis Toxins)
Open AccessArticle Briarenolides U–Y, New Anti-Inflammatory Briarane Diterpenoids from an Octocoral Briareum sp. (Briareidae)
Mar. Drugs 2015, 13(12), 7138-7149; doi:10.3390/md13127060
Received: 8 November 2015 / Revised: 20 November 2015 / Accepted: 25 November 2015 / Published: 3 December 2015
Cited by 3 | PDF Full-text (1103 KB) | HTML Full-text | XML Full-text
Abstract
Five new 13,14-epoxybriarane diterpenoids, briarenolides U–Y (15), were isolated from the octocoral Briareum sp. The structures of briaranes 15 were elucidated by spectroscopic methods. Briarenolides U–Y (15) were found to significantly inhibit the
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Five new 13,14-epoxybriarane diterpenoids, briarenolides U–Y (15), were isolated from the octocoral Briareum sp. The structures of briaranes 15 were elucidated by spectroscopic methods. Briarenolides U–Y (15) were found to significantly inhibit the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Full article
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Open AccessArticle Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3
Mar. Drugs 2015, 13(12), 7250-7274; doi:10.3390/md13127062
Received: 30 September 2015 / Accepted: 25 November 2015 / Published: 5 December 2015
Cited by 3 | PDF Full-text (1254 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
LLG-3 is a ganglioside isolated from the starfish Linchia laevigata. To clarify the structure-activity relationship of the glycan of LLG-3 toward rat pheochromocytoma PC12 cells in the presence of nerve growth factor, a series of mono- to tetrasaccharide glycan derivatives were chemically
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LLG-3 is a ganglioside isolated from the starfish Linchia laevigata. To clarify the structure-activity relationship of the glycan of LLG-3 toward rat pheochromocytoma PC12 cells in the presence of nerve growth factor, a series of mono- to tetrasaccharide glycan derivatives were chemically synthesized and evaluated in vitro. The methyl group at C8 of the terminal sialic acid residue was crucial for neuritogenic activity, and the terminal trisaccharide moiety was the minimum active motif. Furthermore, the trisaccharide also stimulated neuritogenesis in human neuroblastoma SH-SY5Y cells via mitogen-activated protein kinase (MAPK) signaling. Phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was rapidly induced by adding 1 or 10 nM of the trisaccharide. The ratio of phosphorylated ERK to ERK reached a maximum 5 min after stimulation, and then decreased gradually. However, the trisaccharide did not induce significant Akt phosphorylation. These effects were abolished by pretreatment with the MAPK inhibitor U0126, which inhibits enzymes MEK1 and MEK2. In addition, U0126 inhibited the phosphorylation of ERK 1/2 in response to the trisaccharide dose-dependently. Therefore, we concluded that the trisaccharide promotes neurite extension in SH-SY5Y cells via MAPK/ERK signaling, not Akt signaling. Full article
(This article belongs to the Special Issue Marine Glycoconjugates)
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Open AccessFeature PaperArticle Biotechnological Production of Docosahexaenoic Acid Using Aurantiochytrium limacinum: Carbon Sources Comparison And Growth Characterization
Mar. Drugs 2015, 13(12), 7275-7284; doi:10.3390/md13127064
Received: 8 June 2015 / Accepted: 30 November 2015 / Published: 5 December 2015
Cited by 4 | PDF Full-text (471 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aurantiochytrium limacinum, a marine heterotrophic protist/microalga has shown interesting yields of docosahexaenoic acid (DHA) when cultured with different carbon sources: glucose, pure and crude glycerol. A complete study in a lab-scale fermenter allowed for the characterization and comparison of the growth kinetic
[...] Read more.
Aurantiochytrium limacinum, a marine heterotrophic protist/microalga has shown interesting yields of docosahexaenoic acid (DHA) when cultured with different carbon sources: glucose, pure and crude glycerol. A complete study in a lab-scale fermenter allowed for the characterization and comparison of the growth kinetic parameters corresponding to each carbon source. Artificial Marine Medium (AMM) with glucose, pure and crude glycerol offered similar biomass yields. The net growth rates (0.10–0.12 h−1), biomass (0.7–0.8 g cells/g Substrate) and product (0.14–0.15 g DHA/g cells) yields, as well as DHA productivity were similar using the three carbon sources. Viable potential applications to valorize crude glycerol are envisioned to avoid an environmental problem due to the excess of byproduct. Full article
(This article belongs to the Special Issue Marine Lipids)
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Open AccessArticle Isolation and Synthesis of Laxaphycin B-Type Peptides: A Case Study and Clues to Their Biosynthesis
Mar. Drugs 2015, 13(12), 7285-7300; doi:10.3390/md13127065
Received: 15 October 2015 / Accepted: 30 November 2015 / Published: 5 December 2015
Cited by 2 | PDF Full-text (644 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The laxaphyci’s B family constitutes a group of five related cyclic lipopeptides isolated from diverse cyanobacteria from all around the world. This group shares a typical structure of 12 amino acids from the l and d series, some of them hydroxylated at the
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The laxaphyci’s B family constitutes a group of five related cyclic lipopeptides isolated from diverse cyanobacteria from all around the world. This group shares a typical structure of 12 amino acids from the l and d series, some of them hydroxylated at the beta position, and all containing a rare beta-amino decanoic acid. Nevertheless, they can be differentiated due to slight variations in the composition of their amino acids, but the configuration of their alpha carbon remains conserved. Here, we provide the synthesis and characterization of new laxaphycin B-type peptides. In doing so we discuss how the synthesis of laxaphycin B and analogues was developed. We also isolate minor acyclic laxaphycins B, which are considered clues to their biosynthesis. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria)
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Open AccessArticle Long-Term Feeding of Chitosan Ameliorates Glucose and Lipid Metabolism in a High-Fructose-Diet-Impaired Rat Model of Glucose Tolerance
Mar. Drugs 2015, 13(12), 7302-7313; doi:10.3390/md13127067
Received: 29 October 2015 / Revised: 26 November 2015 / Accepted: 1 December 2015 / Published: 10 December 2015
Cited by 5 | PDF Full-text (722 KB) | HTML Full-text | XML Full-text
Abstract
This study was designed to investigate the effects of long-term feeding of chitosan on plasma glucose and lipids in rats fed a high-fructose (HF) diet (63.1%). Male Sprague-Dawley rats aged seven weeks were used as experimental animals. Rats were divided into three groups:
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This study was designed to investigate the effects of long-term feeding of chitosan on plasma glucose and lipids in rats fed a high-fructose (HF) diet (63.1%). Male Sprague-Dawley rats aged seven weeks were used as experimental animals. Rats were divided into three groups: (1) normal group (normal); (2) HF group; (3) chitosan + HF group (HF + C). The rats were fed the experimental diets and drinking water ad libitum for 21 weeks. The results showed that chitosan (average molecular weight was about 3.8 × 105 Dalton and degree of deacetylation was about 89.8%) significantly decreased body weight, paraepididymal fat mass, and retroperitoneal fat mass weight, but elevated the lipolysis rate in retroperitoneal fats of HF diet-fed rats. Supplementation of chitosan causes a decrease in plasma insulin, tumor necrosis factor (TNF)-α, Interleukin (IL)-6, and leptin, and an increase in plasma adiponectin. The HF diet increased hepatic lipids. However, intake of chitosan reduced the accumulation of hepatic lipids, including total cholesterol (TC) and triglyceride (TG) contents. In addition, chitosan elevated the excretion of fecal lipids in HF diet-fed rats. Furthermore, chitosan significantly decreased plasma TC, low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), the TC/high-density lipoprotein cholesterol (HDL-C) ratio, and increased the HDL-C/(LDL-C + VLDL-C) ratio, but elevated the plasma TG and free fatty acids concentrations in HF diet-fed rats. Plasma angiopoietin-like 4 (ANGPTL4) protein expression was not affected by the HF diet, but it was significantly increased in chitosan-supplemented, HF-diet-fed rats. The high-fructose diet induced an increase in plasma glucose and impaired glucose tolerance, but chitosan supplementation decreased plasma glucose and improved impairment of glucose tolerance and insulin tolerance. Taken together, these results indicate that supplementation with chitosan can improve the impairment of glucose and lipid metabolism in a HF-diet-fed rat model. Full article
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Open AccessArticle Carotenoids, Phenolic Compounds and Tocopherols Contribute to the Antioxidative Properties of Some Microalgae Species Grown on Industrial Wastewater
Mar. Drugs 2015, 13(12), 7339-7356; doi:10.3390/md13127069
Received: 15 September 2015 / Revised: 17 November 2015 / Accepted: 2 December 2015 / Published: 11 December 2015
Cited by 20 | PDF Full-text (1075 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed at investigating the potential of microalgae species grown on industrial waste water as a new source of natural antioxidants. Six microalgae from different classes, including Phaeodactylum sp. (Bacillariophyceae), Nannochloropsis sp. (Eustigmatophyceae), Chlorella sp., Dunaniella sp., and Desmodesmus sp. (Chlorophyta), were
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This study aimed at investigating the potential of microalgae species grown on industrial waste water as a new source of natural antioxidants. Six microalgae from different classes, including Phaeodactylum sp. (Bacillariophyceae), Nannochloropsis sp. (Eustigmatophyceae), Chlorella sp., Dunaniella sp., and Desmodesmus sp. (Chlorophyta), were screened for their antioxidant properties using different in vitro assays. Natural antioxidants, including pigments, phenolics, and tocopherols, were measured in methanolic extracts of microalgae biomass. Highest and lowest concentrations of pigments, phenolic compounds, and tocopherols were found in Desmodesmus sp. and Phaeodactylum tricornuotom microalgae species, respectively. The results of each assay were correlated to the content of natural antioxidants in microalgae biomass. Phenolic compounds were found as major contributors to the antioxidant activity in all antioxidant tests while carotenoids were found to contribute to the 1,1-diphenyl-2-picryl-hydrazil (DPPH) radical scavenging activity, ferrous reduction power (FRAP), and ABTS-radical scavenging capacity activity. Desmodesmus sp. biomass represented a potentially rich source of natural antioxidants, such as carotenoids (lutein), tocopherols, and phenolic compounds when cultivated on industrial waste water as the main nutrient source. Full article
(This article belongs to the Special Issue Green Chemistry Approach to Marine Products)
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Open AccessArticle MytiLec, a Mussel R-Type Lectin, Interacts with Surface Glycan Gb3 on Burkitt’s Lymphoma Cells to Trigger Apoptosis through Multiple Pathways
Mar. Drugs 2015, 13(12), 7377-7389; doi:10.3390/md13127071
Received: 1 October 2015 / Revised: 30 November 2015 / Accepted: 2 December 2015 / Published: 14 December 2015
Cited by 10 | PDF Full-text (2854 KB) | HTML Full-text | XML Full-text
Abstract
MytiLec; a novel lectin isolated from the Mediterranean mussel (Mytilus galloprovincialis); shows strong binding affinity to globotriose (Gb3: Galα1-4Galβ1-4Glc). MytiLec revealed β-trefoil folding as also found in the ricin B-subunit type (R-type) lectin family, although the amino acid sequences were quite
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MytiLec; a novel lectin isolated from the Mediterranean mussel (Mytilus galloprovincialis); shows strong binding affinity to globotriose (Gb3: Galα1-4Galβ1-4Glc). MytiLec revealed β-trefoil folding as also found in the ricin B-subunit type (R-type) lectin family, although the amino acid sequences were quite different. Classification of R-type lectin family members therefore needs to be based on conformation as well as on primary structure. MytiLec specifically killed Burkitt's lymphoma Ramos cells, which express Gb3. Fluorescein-labeling assay revealed that MytiLec was incorporated inside the cells. MytiLec treatment of Ramos cells resulted in activation of both classical MAPK/ extracellular signal-regulated kinase and extracellular signal-regulated kinase (MEK-ERK) and stress-activated (p38 kinase and JNK) Mitogen-activated protein kinases (MAPK) pathways. In the cells, MytiLec treatment triggered expression of tumor necrosis factor (TNF)-α (a ligand of death receptor-dependent apoptosis) and activation of mitochondria-controlling caspase-9 (initiator caspase) and caspase-3 (activator caspase). Experiments using the specific MEK inhibitor U0126 showed that MytiLec-induced phosphorylation of the MEK-ERK pathway up-regulated expression of the cyclin-dependent kinase inhibitor p21, leading to cell cycle arrest and TNF-α production. Activation of caspase-3 by MytiLec appeared to be regulated by multiple different pathways. Our findings, taken together, indicate that the novel R-type lectin MytiLec initiates programmed cell death of Burkitt’s lymphoma cells through multiple pathways (MAPK cascade, death receptor signaling; caspase activation) based on interaction of the lectin with Gb3-containing glycosphingolipid-enriched microdomains on the cell surface. Full article
(This article belongs to the Special Issue Marine Glycoconjugates)
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Open AccessArticle Algal Toxin Azaspiracid-1 Induces Early Neuronal Differentiation and Alters Peripherin Isoform Stoichiometry
Mar. Drugs 2015, 13(12), 7390-7402; doi:10.3390/md13127072
Received: 17 August 2015 / Revised: 23 November 2015 / Accepted: 2 December 2015 / Published: 14 December 2015
Cited by 3 | PDF Full-text (3213 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Azaspiracid-1 is an algal toxin that accumulates in edible mussels, and ingestion may result in human illness as manifested by vomiting and diarrhoea. When injected into mice, it causes neurotoxicological symptoms and death. Although it is well known that azaspiracid-1 is toxic to
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Azaspiracid-1 is an algal toxin that accumulates in edible mussels, and ingestion may result in human illness as manifested by vomiting and diarrhoea. When injected into mice, it causes neurotoxicological symptoms and death. Although it is well known that azaspiracid-1 is toxic to most cells and cell lines, little is known about its biological target(s). A rat PC12 cell line, commonly used as a model for the peripheral nervous system, was used to study the neurotoxicological effects of azaspiracid-1. Azaspiracid-1 induced differentiation-related morphological changes followed by a latter cell death. The differentiated phenotype showed peripherin-labelled neurite-like processes simultaneously as a specific isoform of peripherin was down-regulated. The precise mechanism behind this down-regulation remains uncertain. However, this study provides new insights into the neurological effects of azaspiracid-1 and into the biological significance of specific isoforms of peripherin. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
Open AccessArticle Structure-Activity Relationship and in Vivo Anti-Tumor Evaluations of Dictyoceratin-A and -C, Hypoxia-Selective Growth Inhibitors from Marine Sponge
Mar. Drugs 2015, 13(12), 7419-7432; doi:10.3390/md13127074
Received: 2 October 2015 / Revised: 1 December 2015 / Accepted: 3 December 2015 / Published: 16 December 2015
Cited by 5 | PDF Full-text (1500 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Oral dictyoceratin-C (1) and A (2), hypoxia-selective growth inhibitors, showed potent in vivo antitumor effects in mice subcutaneously inoculated with sarcoma S180 cells. Structurally modified analogs were synthesized to assess the structure–activity relationship of the natural compounds 1 and
[...] Read more.
Oral dictyoceratin-C (1) and A (2), hypoxia-selective growth inhibitors, showed potent in vivo antitumor effects in mice subcutaneously inoculated with sarcoma S180 cells. Structurally modified analogs were synthesized to assess the structure–activity relationship of the natural compounds 1 and 2 isolated from a marine sponge. Biological evaluation of these analogs showed that the exo-olefin and hydroxyl and methyl ester moieties were important for the hypoxia-selective growth inhibitory activities of 1 and 2. Thus far, only substitution of the methyl ester with propargyl amide in 1 was found to be effective for the synthesis of probe molecules for target identification. Full article
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Open AccessArticle Generation of Internal-Image Functional Aptamers of Okadaic Acid via Magnetic-Bead SELEX
Mar. Drugs 2015, 13(12), 7433-7445; doi:10.3390/md13127066
Received: 31 March 2015 / Revised: 9 October 2015 / Accepted: 5 November 2015 / Published: 17 December 2015
Cited by 2 | PDF Full-text (2175 KB) | HTML Full-text | XML Full-text
Abstract
Okadaic acid (OA) is produced by Dinophysis and Prorocentrum dinoflagellates and primarily accumulates in bivalves, and this toxin has harmful effects on consumers and operators. In this work, we first report the use of aptamers as novel non-toxic probes capable of binding to
[...] Read more.
Okadaic acid (OA) is produced by Dinophysis and Prorocentrum dinoflagellates and primarily accumulates in bivalves, and this toxin has harmful effects on consumers and operators. In this work, we first report the use of aptamers as novel non-toxic probes capable of binding to a monoclonal antibody against OA (OA-mAb). Aptamers that mimic the OA toxin with high affinity and selectivity were generated by the magnetic bead-assisted systematic evolution of ligands by exponential enrichment (SELEX) strategy. After 12 selection rounds, cloning, sequencing and enzyme-linked immunosorbent assay (ELISA) analysis, four candidate aptamers (O24, O31, O39, O40) were selected that showed high affinity and specificity for OA-mAb. The affinity constants of O24, O31, O39 and O40 were 8.3 × 108 M−1, 1.47 × 109 M−1, 1.23 × 109 M−1 and 1.05 × 109 M−1, respectively. Indirect competitive ELISA was employed to determine the internal-image function of the aptamers. The results reveal that O31 has a similar competitive function as free OA toxin, whereas the other three aptamers did not bear the necessary internal-image function. Based on the derivation of the curvilinear equation for OA/O31, the equation that defined the relationship between the OA toxin content and O31 was Y = 2.185X − 1.78. The IC50 of O31 was 3.39 ng·mL−1, which was close to the value predicted by the OA ELISA (IC50 = 4.4 ng·mL−1); the IC10 was 0.33 ng·mL−1. The above data provides strong evidence that internal-image functional aptamers could be applicable as novel probes in a non-toxic assay. Full article
(This article belongs to the Special Issue Okadaic Acid and Dinophysis Toxins)
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Open AccessArticle Low-Molecular-Weight Fucoidan Induces Endothelial Cell Migration via the PI3K/AKT Pathway and Modulates the Transcription of Genes Involved in Angiogenesis
Mar. Drugs 2015, 13(12), 7446-7462; doi:10.3390/md13127075
Received: 20 November 2015 / Revised: 10 December 2015 / Accepted: 11 December 2015 / Published: 18 December 2015
Cited by 5 | PDF Full-text (1433 KB) | HTML Full-text | XML Full-text
Abstract
Low-molecular-weight fucoidan (LMWF) is a sulfated polysaccharide extracted from brown seaweed that presents antithrombotic and pro-angiogenic properties. However, its mechanism of action is not well-characterized. Here, we studied the effects of LMWF on cell signaling and whole genome expression in human umbilical vein
[...] Read more.
Low-molecular-weight fucoidan (LMWF) is a sulfated polysaccharide extracted from brown seaweed that presents antithrombotic and pro-angiogenic properties. However, its mechanism of action is not well-characterized. Here, we studied the effects of LMWF on cell signaling and whole genome expression in human umbilical vein endothelial cells and endothelial colony forming cells. We observed that LMWF and vascular endothelial growth factor had synergistic effects on cell signaling, and more interestingly that LMWF by itself, in the absence of other growth factors, was able to trigger the activation of the PI3K/AKT pathway, which plays a crucial role in angiogenesis and vasculogenesis. We also observed that the effects of LMWF on cell migration were PI3K/AKT-dependent and that LMWF modulated the expression of genes involved at different levels of the neovessel formation process, such as cell migration and cytoskeleton organization, cell mobilization and homing. This provides a better understanding of LMWF’s mechanism of action and confirms that it could be an interesting therapeutic approach for vascular repair. Full article
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Open AccessArticle Protective Effect of Chitin Urocanate Nanofibers against Ultraviolet Radiation
Mar. Drugs 2015, 13(12), 7463-7475; doi:10.3390/md13127076
Received: 23 July 2015 / Revised: 6 December 2015 / Accepted: 8 December 2015 / Published: 19 December 2015
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Abstract
Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils
[...] Read more.
Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils (NFs). We typically obtain NFs by hydrolyzing chitin with acetic acid. However, in the present study, we used urocanic acid to prepare urocanic acid chitin NFs (UNFs) and examined its protective effect against UVB radiation. Hos: HR-1 mice coated with UNFs were UVB irradiated (302 nm, 150 mJ/cm2), and these mice showed markedly lower UVB radiation-induced cutaneous erythema than the control. Additionally, sunburn cells were rarely detected in the epidermis of UNFs-coated mice after UVB irradiation. Although the difference was not as significant as UNFs, the number of sunburn cells in mice treated with acetic acid chitin nanofibrils (ANFs) tended to be lower than in control mice. These results demonstrate that ANFs have a protective effect against UVB and suggest that the anti-inflammatory and antioxidant effects of NFs influence the protective effect of ANFs against UVB radiation. The combination of NFs with other substances that possess UV-protective effects, such as urocanic acid, may provide an enhanced protective effect against UVB radiation. Full article

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Open AccessReview Potential Threats Posed by New or Emerging Marine Biotoxins in UK Waters and Examination of Detection Methodologies Used for Their Control: Cyclic Imines
Mar. Drugs 2015, 13(12), 7087-7112; doi:10.3390/md13127057
Received: 11 September 2015 / Revised: 28 October 2015 / Accepted: 3 November 2015 / Published: 26 November 2015
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Abstract
Cyclic imines (CIs) are a group of phytoplankton produced toxins related to shellfish food products, some of which are already present in UK and European waters. Their risk to shellfish consumers is poorly understood, as while no human intoxication has been definitively related
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Cyclic imines (CIs) are a group of phytoplankton produced toxins related to shellfish food products, some of which are already present in UK and European waters. Their risk to shellfish consumers is poorly understood, as while no human intoxication has been definitively related to this group, their fast acting toxicity following intraperitoneal injection in mice has led to concern over their human health implications. A request was therefore made by UK food safety authorities to examine these toxins more closely to aid possible management strategies. Of the CI producers only the spirolide producer Alexandrium ostenfeldii is known to exist in UK waters at present but trends in climate change may lead to increased risk from other organisms/CI toxins currently present elsewhere in Europe and in similar environments worldwide. This paper reviews evidence concerning the prevalence of CIs and CI-producing phytoplankton, together with testing methodologies. Chemical, biological and biomolecular methods are reviewed, including recommendations for further work to enable effective testing. Although the focus here is on the UK, from a strategic standpoint many of the topics discussed will also be of interest in other parts of the world since new and emerging marine biotoxins are of global concern. Full article
(This article belongs to the Special Issue Emerging Marine Toxins)
Open AccessFeature PaperReview Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone
Mar. Drugs 2015, 13(12), 7314-7338; doi:10.3390/md13127068
Received: 3 November 2015 / Revised: 22 November 2015 / Accepted: 2 December 2015 / Published: 11 December 2015
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Abstract
The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of
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The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010–2015 have met the expectations of an interdisciplinary audience. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
Open AccessReview Potential Threats Posed by Tetrodotoxins in UK Waters: Examination of Detection Methodology Used in Their Control
Mar. Drugs 2015, 13(12), 7357-7376; doi:10.3390/md13127070
Received: 26 September 2015 / Revised: 30 November 2015 / Accepted: 7 December 2015 / Published: 11 December 2015
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Abstract
Tetrodotoxin is a neurotoxin responsible for many human fatalities, most commonly following the consumption of pufferfish. Whilst the source of the toxin has not been conclusively proven, it is thought to be associated with various species of marine bacteria. Whilst the toxins are
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Tetrodotoxin is a neurotoxin responsible for many human fatalities, most commonly following the consumption of pufferfish. Whilst the source of the toxin has not been conclusively proven, it is thought to be associated with various species of marine bacteria. Whilst the toxins are well studied in fish and gastropods, in recent years, there have been a number of reports of tetrodotoxin occurring in bivalve shellfish, including those harvested from the UK and other parts of Europe. This paper reviews evidence concerning the prevalence of tetrodotoxins in the UK together with methodologies currently available for testing. Biological, biomolecular and chemical methods are reviewed, including recommendations for further work. With the recent development of quantitative chromatographic methods for these and other hydrophilic toxins, as well as the commercial availability of rapid testing kits, there are a number of options available to ensure consumers are protected against this threat. Full article
(This article belongs to the Special Issue Emerging Marine Toxins)
Open AccessReview Distribution in Different Organisms of Amino Acid Oxidases with FAD or a Quinone As Cofactor and Their Role as Antimicrobial Proteins in Marine Bacteria
Mar. Drugs 2015, 13(12), 7403-7418; doi:10.3390/md13127073
Received: 4 November 2015 / Revised: 27 November 2015 / Accepted: 8 December 2015 / Published: 16 December 2015
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Abstract
Amino acid oxidases (AAOs) catalyze the oxidative deamination of amino acids releasing ammonium and hydrogen peroxide. Several kinds of these enzymes have been reported. Depending on the amino acid isomer used as a substrate, it is possible to differentiate between l-amino acid
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Amino acid oxidases (AAOs) catalyze the oxidative deamination of amino acids releasing ammonium and hydrogen peroxide. Several kinds of these enzymes have been reported. Depending on the amino acid isomer used as a substrate, it is possible to differentiate between l-amino acid oxidases and d-amino acid oxidases. Both use FAD as cofactor and oxidize the amino acid in the alpha position releasing the corresponding keto acid. Recently, a novel class of AAOs has been described that does not contain FAD as cofactor, but a quinone generated by post-translational modification of residues in the same protein. These proteins are named as LodA-like proteins, after the first member of this group described, LodA, a lysine epsilon oxidase synthesized by the marine bacterium Marinomonas mediterranea. In this review, a phylogenetic analysis of all the enzymes described with AAO activity has been performed. It is shown that it is possible to recognize different groups of these enzymes and those containing the quinone cofactor are clearly differentiated. In marine bacteria, particularly in the genus Pseudoalteromonas, most of the proteins described as antimicrobial because of their capacity to generate hydrogen peroxide belong to the group of LodA-like proteins. Full article
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Open AccessConference Report The 9th European Conference on Marine Natural Products
Mar. Drugs 2015, 13(12), 7150-7249; doi:10.3390/md13127059
Received: 5 August 2015 / Revised: 23 October 2015 / Accepted: 25 October 2015 / Published: 3 December 2015
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Abstract
The 9th European Conference on Marine Natural Products (ECMNP) in Glasgow follows its predecessors in La Toja (2013), Tjärnö (2011), Porto (2009), Ischia (2007), Paris (2005), Elmau (2002), Santiago de Compostela (1999), and Athens (1997). [...] Full article
Open AccessCorrection Correction: Vinayak, V., et al. Diatom Milking: A Review and New Approaches. Marine Drugs 2015, 13, 2629–2665
Mar. Drugs 2015, 13(12), 7301; doi:10.3390/md13127063
Received: 16 July 2015 / Accepted: 22 July 2015 / Published: 8 December 2015
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