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Mar. Drugs, Volume 15, Issue 6 (June 2017)

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Cover Story The sequencing of biosynthetic pathways allows their biochemistry to be investigated, and in some [...] Read more.
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Open AccessArticle Bioactive Diphenyl Ethers and Isocoumarin Derivatives from a Gorgonian-Derived Fungus Phoma sp. (TA07-1)
Mar. Drugs 2017, 15(6), 146; doi:10.3390/md15060146
Received: 25 March 2017 / Revised: 11 May 2017 / Accepted: 23 May 2017 / Published: 25 May 2017
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Abstract
Three new diphenyl ether derivatives—phomaethers A–C (13) and five known compounds—including a diphenyl ether analog, 2,3′-dihydroxy-4-methoxy-5′,6-dimethyl diphenyl ether (4); and four isocoumarin derivatives, diaportinol (5), desmethyldiaportinol (6), citreoisocoumarinol (7), and citreoisocoumarin
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Three new diphenyl ether derivatives—phomaethers A–C (13) and five known compounds—including a diphenyl ether analog, 2,3′-dihydroxy-4-methoxy-5′,6-dimethyl diphenyl ether (4); and four isocoumarin derivatives, diaportinol (5), desmethyldiaportinol (6), citreoisocoumarinol (7), and citreoisocoumarin (8)—were isolated from a gorgonian-derived fungus Phoma sp. (TA07-1). Their structures were elucidated by extensive spectroscopic investigation. The absolute configurations of 1 and 2 were determined by acid hydrolysis reactions. It was the first report to discover the diphenyl glycoside derivatives from coral-derived fungi. Compounds 1, 3, and 4 showed selective strong antibacterial activity against five pathogenic bacteria with the minimum inhibiting concentration (MIC) values and minimum bactericidal concentration (MBC) values between 0.156 and 10.0 μM. Full article
(This article belongs to the Special Issue Marine Bioactive Natural Product Studies in Asia)
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Open AccessArticle Taurine Biosynthesis in a Fish Liver Cell Line (ZFL) Adapted to a Serum-Free Medium
Mar. Drugs 2017, 15(6), 147; doi:10.3390/md15060147
Received: 1 April 2017 / Revised: 18 May 2017 / Accepted: 22 May 2017 / Published: 25 May 2017
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Abstract
Although taurine has been shown to play multiple important physiological roles in teleosts, little is known about the molecular mechanisms underlying dietary requirements. Cell lines can provide useful tools for deciphering biosynthetic pathways and their regulation. However, culture media and sera contain variable
[...] Read more.
Although taurine has been shown to play multiple important physiological roles in teleosts, little is known about the molecular mechanisms underlying dietary requirements. Cell lines can provide useful tools for deciphering biosynthetic pathways and their regulation. However, culture media and sera contain variable taurine levels. To provide a useful cell line for the investigation of taurine homeostasis, an adult zebrafish liver cell line (ZFL) has been adapted to a taurine-free medium by gradual accommodation to a commercially available synthetic medium, UltraMEM™-ITES. Here we show that ZFL cells are able to synthesize taurine and be maintained in medium without taurine. This has allowed for the investigation of the effects of taurine supplementation on cell growth, cellular amino acid pools, as well as the expression of the taurine biosynthetic pathway and taurine transporter genes in a defined fish cell type. After taurine supplementation, cellular taurine levels increase but hypotaurine levels stay constant, suggesting little suppression of taurine biosynthesis. Cellular methionine levels do not change after taurine addition, consistent with maintenance of taurine biosynthesis. The addition of taurine to cells grown in taurine-free medium has little effect on transcript levels of the biosynthetic pathway genes for cysteine dioxygenase (CDO), cysteine sulfinate decarboxylase (CSAD), or cysteamine dioxygenase (ADO). In contrast, supplementation with taurine causes a 30% reduction in transcript levels of the taurine transporter, TauT. This experimental approach can be tailored for the development of cell lines from aquaculture species for the elucidation of their taurine biosynthetic capacity. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessArticle Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ
Mar. Drugs 2017, 15(6), 148; doi:10.3390/md15060148
Received: 9 February 2017 / Revised: 28 April 2017 / Accepted: 18 May 2017 / Published: 25 May 2017
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Abstract
The peroxisome proliferator-activated receptors (PPARs) function as ligand-activated transcription factors that convert signals in the form of lipids to physiological responses through the activation of metabolic target genes. Due to their key roles in lipid and carbohydrate metabolism, the PPARs are important drug
[...] Read more.
The peroxisome proliferator-activated receptors (PPARs) function as ligand-activated transcription factors that convert signals in the form of lipids to physiological responses through the activation of metabolic target genes. Due to their key roles in lipid and carbohydrate metabolism, the PPARs are important drug targets. However, for several of the PPAR drugs currently in use, adverse side effects have been reported. In an effort to identify compounds from marine organisms that may serve as molecular scaffolds for the development of novel and safer PPAR-targeting drugs, we performed a bioassay-guided screening of organic extracts made from organisms supplied by the Norwegian Biobank of Arctic Marine Organisms (Marbank). Among several interesting hits, we identified two poorly described isomeric oxo-fatty acids from the microalgae Chaetoceros karianus for which we provide the first evidence that they might display dual specificity towards human PPARα and PPARγ. Principal component analysis showed that C. karianus stood out from other Chaetoceros species, both with respect to the metabolic profile and the PPAR activity. The isolation of these compounds holds the potential of uncovering a PPAR pharmacophore with tunable activity and specificity. Full article
(This article belongs to the collection Bioactive Compounds from Marine Plankton)
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Open AccessArticle Characterization of Acetyl-CoA Carboxylases in the Basal Dinoflagellate Amphidinium carterae
Mar. Drugs 2017, 15(6), 149; doi:10.3390/md15060149
Received: 29 March 2017 / Revised: 20 May 2017 / Accepted: 23 May 2017 / Published: 26 May 2017
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Abstract
Dinoflagellates make up a diverse array of fatty acids and polyketides. A necessary precursor for their synthesis is malonyl-CoA formed by carboxylating acetyl CoA using the enzyme acetyl-CoA carboxylase (ACC). To date, information on dinoflagellate ACC is limited. Through transcriptome analysis in Amphidinium
[...] Read more.
Dinoflagellates make up a diverse array of fatty acids and polyketides. A necessary precursor for their synthesis is malonyl-CoA formed by carboxylating acetyl CoA using the enzyme acetyl-CoA carboxylase (ACC). To date, information on dinoflagellate ACC is limited. Through transcriptome analysis in Amphidinium carterae, we found three full-length homomeric type ACC sequences; no heteromeric type ACC sequences were found. We assigned the putative cellular location for these ACCs based on transit peptide predictions. Using streptavidin Western blotting along with mass spectrometry proteomics, we validated the presence of ACC proteins. Additional bands showing other biotinylated proteins were also observed. Transcript abundance for these ACCs follow the global pattern of expression for dinoflagellate mRNA messages over a diel cycle. This is one of the few descriptions at the transcriptomic and protein level of ACCs in dinoflagellates. This work provides insight into the enzymes which make the CoA precursors needed for fatty acid and toxin synthesis in dinoflagellates. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessArticle Two New Oxodolastane Diterpenes from the Jamaican Macroalga Canistrocarpus cervicornis
Mar. Drugs 2017, 15(6), 150; doi:10.3390/md15060150
Received: 7 April 2017 / Revised: 9 May 2017 / Accepted: 22 May 2017 / Published: 30 May 2017
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Abstract
The chemical investigation of the organic extract of Canistrocarpus cervicornis, collected at Drunken Man’s Cay at Port Royal, Jamaica, has led to the isolation of two new dolastane diterpenes 4R-acetoxy-8S,9S-epoxy-14S-hydroxy-7-oxodolastane (1) and 4
[...] Read more.
The chemical investigation of the organic extract of Canistrocarpus cervicornis, collected at Drunken Man’s Cay at Port Royal, Jamaica, has led to the isolation of two new dolastane diterpenes 4R-acetoxy-8S,9S-epoxy-14S-hydroxy-7-oxodolastane (1) and 4R-hydroxy-8S,9S-epoxy-14S-hydroxy-7-oxodolastane (2) and the previously isolated dolastane (4R,9S,14S)-4,9,14-trihydroxydolast-1(15),7-diene (3) as a major diterpene constituent. The structures of the new compounds were elucidated by extensive spectroscopic analyses. Compounds 13 were evaluated for their cytotoxicity against human tumor cell lines PC3 and HT29. The results revealed that the dolastane diterpenes (13) displayed moderate, concentration dependent, cytotoxicity. Full article
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Open AccessArticle Enhancement of Biomass and Lipid Productivities of Water Surface-Floating Microalgae by Chemical Mutagenesis
Mar. Drugs 2017, 15(6), 151; doi:10.3390/md15060151
Received: 31 January 2017 / Revised: 19 May 2017 / Accepted: 24 May 2017 / Published: 27 May 2017
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Abstract
Water surface-floating microalgae have great potential for biofuel applications due to the ease of the harvesting process, which is one of the most problematic steps in conventional microalgal biofuel production. We have collected promising water surface-floating microalgae and characterized their capacity for biomass
[...] Read more.
Water surface-floating microalgae have great potential for biofuel applications due to the ease of the harvesting process, which is one of the most problematic steps in conventional microalgal biofuel production. We have collected promising water surface-floating microalgae and characterized their capacity for biomass and lipid production. In this study, we performed chemical mutagenesis of two water surface-floating microalgae to elevate productivity. Floating microalgal strains AVFF007 and FFG039 (tentatively identified as Botryosphaerella sp. and Chlorococcum sp., respectively) were exposed to ethyl methane sulfonate (EMS) or 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), and pale green mutants (PMs) were obtained. The most promising FFG039 PM formed robust biofilms on the surface of the culture medium, similar to those formed by wild type strains, and it exhibited 1.7-fold and 1.9-fold higher biomass and lipid productivities than those of the wild type. This study indicates that the chemical mutation strategy improves the lipid productivity of water surface-floating microalgae without inhibiting biofilm formation and floating ability. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessArticle Collagen from the Marine Sponges Axinella cannabina and Suberites carnosus: Isolation and Morphological, Biochemical, and Biophysical Characterization
Mar. Drugs 2017, 15(6), 152; doi:10.3390/md15060152
Received: 22 April 2017 / Revised: 22 April 2017 / Accepted: 25 May 2017 / Published: 29 May 2017
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Abstract
In search of alternative and safer sources of collagen for biomedical applications, the marine demosponges Axinella cannabina and Suberites carnosus, collected from the Aegean and the Ionian Seas, respectively, were comparatively studied for their insoluble collagen, intercellular collagen, and spongin-like collagen content.
[...] Read more.
In search of alternative and safer sources of collagen for biomedical applications, the marine demosponges Axinella cannabina and Suberites carnosus, collected from the Aegean and the Ionian Seas, respectively, were comparatively studied for their insoluble collagen, intercellular collagen, and spongin-like collagen content. The isolated collagenous materials were morphologically, physicochemically, and biophysically characterized. Using scanning electron microscopy and transmission electron microscopy the fibrous morphology of the isolated collagens was confirmed, whereas the amino acid analysis, in conjunction with infrared spectroscopy studies, verified the characteristic for the collagen amino acid profile and its secondary structure. Furthermore, the isoelectric point and thermal behavior were determined by titration and differential scanning calorimetry, in combination with circular dichroism spectroscopic studies, respectively. Full article
(This article belongs to the Special Issue Collagen from Marine Biological Source and Medical Applications)
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Open AccessCommunication Chalcomycins from Marine-Derived Streptomyces sp. and Their Antimicrobial Activities
Mar. Drugs 2017, 15(6), 153; doi:10.3390/md15060153
Received: 8 March 2017 / Revised: 10 May 2017 / Accepted: 22 May 2017 / Published: 29 May 2017
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Abstract
Dihydrochalcomycin (1) and chalcomycin, (2), two known chalcomycins, and chalcomycin E (3), a new compound, were isolated from marine-derived Streptomyces sp. HK-2006-1. Their structures were elucidated by detailed spectroscopic and X-ray crystallographic analysis. The antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans,
[...] Read more.
Dihydrochalcomycin (1) and chalcomycin, (2), two known chalcomycins, and chalcomycin E (3), a new compound, were isolated from marine-derived Streptomyces sp. HK-2006-1. Their structures were elucidated by detailed spectroscopic and X-ray crystallographic analysis. The antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger of 1–3 were evaluated. Compounds 1–2 exhibited activities against S. aureus with minimal inhibitory concentrations (MICs) of 32 µg/mL and 4 µg/mL, respectively. The fact that 1–2 showed stronger activity against S. aureus 209P than 3 indicated that the epoxy unit was important for antimicrobial activity. This structure–activity tendency of chalcomycins against S. aureus is different from that of aldgamycins reported in our previous research, which provide a valuable example for the phenomenon that 16-membered macrolides with different sugars do not have parallel structure–activity relationships. Full article
(This article belongs to the Special Issue Antibacterial Marine Pharmacology)
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Open AccessArticle Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells
Mar. Drugs 2017, 15(6), 154; doi:10.3390/md15060154
Received: 12 April 2017 / Revised: 16 May 2017 / Accepted: 22 May 2017 / Published: 30 May 2017
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Abstract
It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here,
[...] Read more.
It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investigated the anticancer effect of fucoidan on two p53 isogenic HCT116 (p53+/+ and p53−/−) cell lines. Our results showed that inhibition of cell viability, induction of apoptosis and DNA damage by treatment with fucoidan were similar in two cell lines. Flow cytometric analysis revealed that fucoidan resulted in G1 arrest in the cell cycle progression, which correlated with the inhibition of phosphorylation of retinoblastoma protein (pRB) and concomitant association of pRB with the transcription factor E2Fs. Furthermore, treatment with fucoidan obviously upregulated the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21WAF1/CIP1 and p27KIP1, which was paralleled by an enhanced binding with CDK2 and CDK4. These events also commonly occurred in both cell lines, suggesting that fucoidan triggered G1 arrest and apoptosis in HCT116 cells by a p53-independent mechanism. Thus, given that most tumors exhibit functional p53 inactivation, fucoidan could be a possible therapeutic option for cancer treatment regardless of the p53 status. Full article
(This article belongs to the Special Issue Marine Oligosaccharides and Polysaccharides)
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Open AccessArticle Salt Sensitive Tet-Off-Like Systems to Knockdown Primordial Germ Cell Genes for Repressible Transgenic Sterilization in Channel Catfish, Ictalurus punctatus
Mar. Drugs 2017, 15(6), 155; doi:10.3390/md15060155
Received: 1 April 2017 / Revised: 22 May 2017 / Accepted: 25 May 2017 / Published: 31 May 2017
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Abstract
Repressible knockdown approaches were investigated for transgenic sterilization in channel catfish, Ictalurus punctatus. Two primordial germ cell (PGC) marker genes, nanos and dead end, were targeted for knockdown, and an off-target gene, vasa, was monitored. Two potentially salt sensitive repressible
[...] Read more.
Repressible knockdown approaches were investigated for transgenic sterilization in channel catfish, Ictalurus punctatus. Two primordial germ cell (PGC) marker genes, nanos and dead end, were targeted for knockdown, and an off-target gene, vasa, was monitored. Two potentially salt sensitive repressible promoters, zebrafish adenylosuccinate synthase 2 (ADSS) and zebrafish racemase (Rm), were each coupled with four knockdown strategies: ds-sh RNA targeting the 5′ end (N1) or 3′ end (N2) of channel catfish nanos, full-length cDNA sequence of channel catfish nanos for overexpression (cDNA) and ds-sh RNA targeting channel catfish dead end (DND). Each construct had an untreated group and treated group with sodium chloride as the repressor compound. Spawning rates of full-sibling P1 fish exposed or not exposed to the constructs as treated and untreated embryos were 93% and 59%, respectively, indicating potential sterilization of fish and repression of the constructs. Although the mRNA expression data of PGC marker genes were inconsistent in P1 fish, most F1 individuals were able to downregulate the target genes in untreated groups and repress the knockdown process in treated groups. The results indicate that repressible transgenic sterilization is feasible for reproductive control of fish, but more data from F2 or F3 are needed for evaluation. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessArticle Characterization and Genome Analysis of a Nicotine and Nicotinic Acid-Degrading Strain Pseudomonas putida JQ581 Isolated from Marine
Mar. Drugs 2017, 15(6), 156; doi:10.3390/md15060156
Received: 14 January 2017 / Revised: 10 April 2017 / Accepted: 25 May 2017 / Published: 31 May 2017
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Abstract
The presence of nicotine and nicotinic acid (NA) in the marine environment has caused great harm to human health and the natural environment. Therefore, there is an urgent need to use efficient and economical methods to remove such pollutants from the environment. In
[...] Read more.
The presence of nicotine and nicotinic acid (NA) in the marine environment has caused great harm to human health and the natural environment. Therefore, there is an urgent need to use efficient and economical methods to remove such pollutants from the environment. In this study, a nicotine and NA-degrading bacterium—strain JQ581—was isolated from sediment from the East China Sea and identified as a member of Pseudomonas putida based on morphology, physio-biochemical characteristics, and 16S rDNA gene analysis. The relationship between growth and nicotine/NA degradation suggested that strain JQ581 was a good candidate for applications in the bioaugmentation treatment of nicotine/NA contamination. The degradation intermediates of nicotine are pseudooxynicotine (PN) and 3-succinoyl-pyridine (SP) based on UV, high performance liquid chromatography, and liquid chromatography-mass spectrometry analyses. However, 6-hydroxy-3-succinoyl-pyridine (HSP) was not detected. NA degradation intermediates were identified as 6-hydroxynicotinic acid (6HNA). The whole genome of strain JQ581 was sequenced and analyzed. Genome sequence analysis revealed that strain JQ581 contained the gene clusters for nicotine and NA degradation. This is the first report where a marine-derived Pseudomonas strain had the ability to degrade nicotine and NA simultaneously. Full article
(This article belongs to the Special Issue Biotransformations Utilizing Marine/Marine-Derived Bacteria and Fungi)
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Open AccessArticle The Missing Piece in Biosynthesis of Amphidinols: First Evidence of Glycolate as a Starter Unit in New Polyketides from Amphidinium carterae
Mar. Drugs 2017, 15(6), 157; doi:10.3390/md15060157
Received: 28 April 2017 / Revised: 22 May 2017 / Accepted: 25 May 2017 / Published: 31 May 2017
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Abstract
Two new members of the amphidinol family, amphidinol A (1) and its 7-sulfate derivative amphidinol B (2), were isolated from a strain of Amphidinium carterae of Lake Fusaro, near Naples (Italy), and chemically identified by spectroscopic and spectrometric methods.
[...] Read more.
Two new members of the amphidinol family, amphidinol A (1) and its 7-sulfate derivative amphidinol B (2), were isolated from a strain of Amphidinium carterae of Lake Fusaro, near Naples (Italy), and chemically identified by spectroscopic and spectrometric methods. Amphidinol A showed antifungal activity against Candida albicans (MIC = 19 µg/mL). Biosynthetic experiments with stable isotope-labelled acetate allowed defining the elongation process in 1. For the first time the use of glycolate as a starter unit in the polyketide biosynthesis of amphidinol metabolites was unambiguously demonstrated. Full article
(This article belongs to the Special Issue Marine Microalgae)
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Open AccessArticle A Study of 11-[3H]-Tetrodotoxin Absorption, Distribution, Metabolism and Excretion (ADME) in Adult Sprague-Dawley Rats
Mar. Drugs 2017, 15(6), 159; doi:10.3390/md15060159
Received: 23 April 2017 / Revised: 19 May 2017 / Accepted: 25 May 2017 / Published: 2 June 2017
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Abstract
Tetrodotoxin (TTX) is a powerful sodium channel blocker that in low doses can safely relieve severe pain. Studying the absorption, distribution, metabolism and excretion (ADME) of TTX is challenging given the extremely low lethal dose. We conducted radiolabeled ADME studies in Sprague-Dawley rats.
[...] Read more.
Tetrodotoxin (TTX) is a powerful sodium channel blocker that in low doses can safely relieve severe pain. Studying the absorption, distribution, metabolism and excretion (ADME) of TTX is challenging given the extremely low lethal dose. We conducted radiolabeled ADME studies in Sprague-Dawley rats. After a single dose of 6 μg/(16 μCi/kg) 11-[3H]TTX, pharmacokinetics of plasma total radioactivity were similar in male and female rats. Maximum radioactivity (5.56 ng Eq./mL) was reached in 10 min. [3H]TTX was below detection in plasma after 24 h. The area under the curve from 0 to 8 h was 5.89 h·ng Eq./mL; mean residence time was 1.62 h and t½ was 2.31 h. Bile secretion accounted for 0.43% and approximately 51% of the dose was recovered in the urine, the predominant route of elimination. Approximately 69% was recovered, suggesting that hydrogen tritium exchange in rats produced tritiated water excreted in breath and saliva. Average total radioactivity in the stomach, lungs, kidney and intestines was higher than plasma concentrations. Metabolite analysis of plasma, urine and feces samples demonstrated oxidized TTX, the only identified metabolite. In conclusion, TTX was rapidly absorbed and excreted in rats, a standard preclinical model used to guide the design of clinical trials. Full article
(This article belongs to the Special Issue Tetrodotoxin)
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Open AccessArticle Isolation, Amino Acid Sequences, and Plausible Functions of the Galacturonic Acid-Binding Egg Lectin of the Sea Hare Aplysia kurodai
Mar. Drugs 2017, 15(6), 161; doi:10.3390/md15060161
Received: 31 March 2017 / Revised: 12 May 2017 / Accepted: 25 May 2017 / Published: 2 June 2017
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Abstract
Egg lectins occur in a variety of animals ranging from mollusks to vertebrates. A few examples of molluscan egg lectins have been reported, including that of the sea hare Aplysia kurodai; however, their biological functions in the egg remain unclarified. We report
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Egg lectins occur in a variety of animals ranging from mollusks to vertebrates. A few examples of molluscan egg lectins have been reported, including that of the sea hare Aplysia kurodai; however, their biological functions in the egg remain unclarified. We report the isolation, determination of primary structure, and possible functions of A. kurodai lectin (AKL) from the egg mass of A. kurodai. We obtained AKL as an inseparable mixture of isoproteins with a relative molecular mass of approximately 32 kDa by affinity purification. The hemagglutinating activity of AKL against rabbit erythrocytes was inhibited most potently by galacturonic acid and moderately by xylose. Nucleotide sequencing of corresponding cDNA obtained by rapid amplification of cDNA ends (RACE) allowed us to deduce complete amino acid sequences. The mature polypeptides consisted of 218- or 219-amino acids with three repeated domains. The amino acid sequence had similarities to hypothetical proteins of Aplysia spp., or domain DUF3011 of uncharacterized bacterial proteins. AKL is the first member of the DUF3011 family whose function, carbohydrate recognition, was revealed. Treatment of the egg with galacturonic acid, an AKL sugar inhibitor, resulted in deformation of the veliger larvae, suggesting that AKL is involved in organogenesis in the developmental stage of A. kurodai. Full article
(This article belongs to the Special Issue Structures, Functions and Applications of Marine Lectins)
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Open AccessArticle Running the Stop Sign: Readthrough of a Premature UAG Termination Signal in the Translation of a Zebrafish (Danio rerio) Taurine Biosynthetic Enzyme
Mar. Drugs 2017, 15(6), 162; doi:10.3390/md15060162
Received: 17 March 2017 / Revised: 22 May 2017 / Accepted: 30 May 2017 / Published: 3 June 2017
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Abstract
The UAG termination codon is generally recognized as the least efficient and least frequently used of the three universal stop codons. This is substantiated by numerous studies in an array of organisms. We present here evidence of a translational readthrough of a mutant
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The UAG termination codon is generally recognized as the least efficient and least frequently used of the three universal stop codons. This is substantiated by numerous studies in an array of organisms. We present here evidence of a translational readthrough of a mutant nonsense UAG codon in the transcript from the cysteine sulfinic acid decarboxylase (csad) gene (ENSDARG00000026348) in zebrafish. The csad gene encodes the terminal enzyme in the taurine biosynthetic pathway. Taurine is a critical amino acid for all animals, playing several essential roles throughout the body, including modulation of the immune system. The sa9430 zebrafish strain (ZDB-ALT-130411-5055) has a point mutation leading to a premature stop codon (UAG) 20 amino acids 5’ of the normal stop codon, UGA. Data from immunoblotting, enzyme activity assays, and mass spectrometry provide evidence that the mutant is making a CSAD protein identical to that of the wild-type (XP_009295318.1) in terms of size, activity, and amino acid sequence. UAG readthrough has been described in several species, but this is the first presentation of a case in fish. Also presented are the first data substantiating the ability of a fish CSAD to utilize cysteic acid, an alternative to the standard substrate cysteine sulfinic acid, to produce taurine. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessArticle Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models
Mar. Drugs 2017, 15(6), 163; doi:10.3390/md15060163
Received: 8 February 2017 / Revised: 27 May 2017 / Accepted: 1 June 2017 / Published: 3 June 2017
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Abstract
The goal of this study was to examine the effects of xyloketal B on nonalcoholic fatty liver disease (NAFLD) and to explore the molecular mechanisms underlying its effects in both in vivo and in vitro models. We discovered an association between xyloketal B
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The goal of this study was to examine the effects of xyloketal B on nonalcoholic fatty liver disease (NAFLD) and to explore the molecular mechanisms underlying its effects in both in vivo and in vitro models. We discovered an association between xyloketal B and the sterol regulatory element-binding protein-1c (SREBP-1c) signaling pathway, which is related to lipid metabolism. Mice were dosed with xyloketal B (5, 10 and 20 mg/kg/d) and atorvastatin (15 mg/kg/d) via intraperitoneal injection once daily for 40 days after being fed a high fat diet plus 10% high fructose liquid (HFD+HFL) for 8 weeks. Xyloketal B significantly improved HFD+HFL-induced hepatic histological lesions and attenuated lipid and glucose accumulation in the blood as well as lipid accumulation in the liver. Xyloketal B increased the expression of CPT1A, and decreased the expression of SREBP-1c and its downstream targeting enzymes such as ACC1, ACL, and FAS. Xyloketal B also significantly reduced lipid accumulation in HepG2 cells treated with free fatty acids (FFAs). These data suggested that xyloketal B has lipid-lowering effects via the SREBP-1c pathway that regulate lipid metabolism. Thus, targeting SREBP-1c activation with xyloketal B may be a promising novel approach for NAFLD treatment. Full article
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Open AccessArticle A Novel Lid-Covering Peptide Inhibitor of Nicotinic Acetylcholine Receptors Derived from αD-Conotoxin GeXXA
Mar. Drugs 2017, 15(6), 164; doi:10.3390/md15060164
Received: 24 April 2017 / Revised: 28 May 2017 / Accepted: 31 May 2017 / Published: 5 June 2017
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Abstract
Nicotinic acetylcholine receptors (nAChRs) play a fundamental role in nervous signal transmission, therefore various antagonists and agonists are highly desired to explore the structure and function of nAChRs. Recently, a novel dimeric αD-conotoxin GeXXA was identified to inhibit nAChRs by binding at the
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Nicotinic acetylcholine receptors (nAChRs) play a fundamental role in nervous signal transmission, therefore various antagonists and agonists are highly desired to explore the structure and function of nAChRs. Recently, a novel dimeric αD-conotoxin GeXXA was identified to inhibit nAChRs by binding at the top surface of the receptors, and the monomeric C-terminal domain (CTD) of αD-GeXXA retains some inhibitory activity. In this study, the internal dimeric N-terminal domain (NTD) of this conopeptide was further investigated. We first developed a regio-selective protection strategy to chemically prepare the anti-parallel dimeric NTD, and found that the isolated NTD part of GeXXA possesses the nAChR-inhibitory activity, the subtype-dependence of which implies a preferred binding of NTD to the β subunits of nAChR. Deletion of the NTD N-terminal residues did not affect the activity of NTD, indicating that the N-terminus is not involved in the interaction with nAChRs. By optimizing the sequence of NTD, we obtained a fully active single-chain cyclic NTD, based on which 4 Arg residues were found to interact with nAChRs. These results demonstrate that the NTD part of αD-GeXXA is a “lid-covering” nAChR inhibitor, displaying a novel inhibitory mechanism distinct from other allosteric ligands of nAChRs. Full article
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Open AccessArticle Borrelidins C–E: New Antibacterial Macrolides from a Saltern-Derived Halophilic Nocardiopsis sp.
Mar. Drugs 2017, 15(6), 166; doi:10.3390/md15060166
Received: 29 April 2017 / Revised: 25 May 2017 / Accepted: 2 June 2017 / Published: 6 June 2017
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Abstract
Chemical investigation of a halophilic actinomycete strain belonging to the genus Nocardiopsis inhabiting a hypersaline saltern led to the discovery of new 18-membered macrolides with nitrile functionality, borrelidins C–E (13), along with a previously reported borrelidin (4).
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Chemical investigation of a halophilic actinomycete strain belonging to the genus Nocardiopsis inhabiting a hypersaline saltern led to the discovery of new 18-membered macrolides with nitrile functionality, borrelidins C–E (13), along with a previously reported borrelidin (4). The planar structures of borrelidins C–E, which are new members of the rare borrelidin class of antibiotics, were elucidated by NMR, mass, IR, and UV spectroscopic analyses. The configurations of borrelidines C–E were determined by the interpretation of ROESY NMR spectra, J-based configuration analysis, a modified Mosher’s method, and CD spectroscopic analysis. Borrelidins C and D displayed inhibitory activity, particularly against the Gram-negative pathogen Salmonella enterica, and moderate cytotoxicity against the SNU638 and K562 carcinoma cell lines. Full article
(This article belongs to the Special Issue Antibacterial Marine Pharmacology)
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Open AccessArticle Synergistic Antibacterial Effects of Chitosan-Caffeic Acid Conjugate against Antibiotic-Resistant Acne-Related Bacteria
Mar. Drugs 2017, 15(6), 167; doi:10.3390/md15060167
Received: 17 February 2017 / Revised: 2 June 2017 / Accepted: 6 June 2017 / Published: 8 June 2017
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Abstract
The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, one of the most common skin diseases. Acne vulgaris is often associated with acne-related bacteria such as Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus
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The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, one of the most common skin diseases. Acne vulgaris is often associated with acne-related bacteria such as Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa. Some of these bacteria exhibit a resistance against commercial antibiotics that have been used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin). In the current study, we tested in vitro antibacterial effect of chitosan-phytochemical conjugates on acne-related bacteria. Three chitosan-phytochemical conjugates used in this study exhibited stronger antibacterial activity than that of chitosan (unmodified control). Chitosan-caffeic acid conjugate (CCA) showed the highest antibacterial effect on acne-related bacteria along with minimum inhibitory concentration (MIC; 8 to 256 μg/mL). Additionally, the MIC values of antibiotics against antibiotic-resistant P. acnes and P. aeruginosa strains were dramatically reduced in combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration (FIC) indices clearly revealed a synergistic antibacterial effect of CCA with antibiotics. Thus, the median sum of FIC (∑FIC) values against the antibiotic-resistant bacterial strains ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics. The results of the present study suggested a potential possibility of chitosan-phytochemical conjugates in the control of infections related to acne vulgaris. Full article
(This article belongs to the Special Issue Antibacterial Marine Pharmacology)
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Open AccessArticle Higher Anti-Liver Fibrosis Effect of Cordyceps militaris-Fermented Product Cultured with Deep Ocean Water via Inhibiting Proinflammatory Factors and Fibrosis-Related Factors Expressions
Mar. Drugs 2017, 15(6), 168; doi:10.3390/md15060168
Received: 2 February 2017 / Revised: 26 March 2017 / Accepted: 1 June 2017 / Published: 8 June 2017
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Abstract
Deep ocean water (DOW) has been shown to enhance the functional components of fungi, resulting in increased health benefits. Therefore, using DOW for culturing fungi can enhance the cordycepin and adenosine of Cordyceps militaris (CM) and its protective effects on the liver. In
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Deep ocean water (DOW) has been shown to enhance the functional components of fungi, resulting in increased health benefits. Therefore, using DOW for culturing fungi can enhance the cordycepin and adenosine of Cordyceps militaris (CM) and its protective effects on the liver. In this study, the antiliver fibrosis effects and mechanisms of ultrapure water-cultured CM (UCM), DOW-cultured CM (DCM), synthetic water-cultured CM, DOW, cordycepin, and adenosine were compared in the liver fibrosis mice induced by intraperitoneal injections of thioacetamide (TAA). The results indicated that DCM exhibited superior performance in reducing liver collagen accumulation, mitigating liver injuries, inhibiting proinflammatory factors and fibrosis-related factor (TGF-β1, Smad2/3, α-SMA, COL1A1) expression compared with UCM. DOW, cordycepin, and adenosine also performed antiliver fibrosis effect. Therefore, because DCM is rich in DOW and functional components, it can achieve anti-liver fibrosis effects through multiple pathways. These ameliorative effects are considerably superior to those of UCM. Full article
(This article belongs to the Special Issue Marine Compounds and Inflammation II, 2017)
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Open AccessArticle Trichodermanins C–E, New Diterpenes with a Fused 6-5-6-6 Ring System Produced by a Marine Sponge-Derived Fungus
Mar. Drugs 2017, 15(6), 169; doi:10.3390/md15060169
Received: 10 May 2017 / Revised: 6 June 2017 / Accepted: 6 June 2017 / Published: 9 June 2017
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Abstract
Trichodermanins C–E (13), new diterpenes with a rare fused 6-5-6-6 ring system, have been isolated from a fungus Trichoderma harzianum OUPS-111D-4 separated from a piece of a marine sponge Halichondria okadai, and these chemical structures have been established
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Trichodermanins C–E (13), new diterpenes with a rare fused 6-5-6-6 ring system, have been isolated from a fungus Trichoderma harzianum OUPS-111D-4 separated from a piece of a marine sponge Halichondria okadai, and these chemical structures have been established by spectroscopic analyses using IR, MASS, HRFABMS, and NMR spectra. We established their absolute stereostructures by application of the modified Mosher’s method. In addition, 1 inhibited the growth of cancer cell lines potently. Full article
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Open AccessArticle Identification of a Novel O-Conotoxin Reveals an Unusual and Potent Inhibitor of the Human α9α10 Nicotinic Acetylcholine Receptor
Mar. Drugs 2017, 15(6), 170; doi:10.3390/md15060170
Received: 5 April 2017 / Revised: 30 May 2017 / Accepted: 6 June 2017 / Published: 9 June 2017
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Abstract
Conotoxins are a pool of disulfide-rich peptide neurotoxins produced by cone snails for predation and defense. They are a rich reservoir of novel ligands for ion channels, neurotransmitter receptors and transporters in the nervous system. In this study, we identified a novel conotoxin
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Conotoxins are a pool of disulfide-rich peptide neurotoxins produced by cone snails for predation and defense. They are a rich reservoir of novel ligands for ion channels, neurotransmitter receptors and transporters in the nervous system. In this study, we identified a novel conotoxin component, O-conotoxin GeXXVIIA, from the venom of Conus generalis. The native form of this component is a disulfide-linked homodimer of a 5-Cys-containing peptide. Surprisingly, our electrophysiological studies showed that, in comparison to the folded monomers, the linear peptide of this toxin had the highest inhibitory activity at the human α9α10 nicotinic acetylcholine receptor (nAChR), with an IC50 of 16.2 ± 1.4 nM. The activities of the N-terminal and C-terminal halves of the linear toxin are markedly reduced compared with the full-length toxin, suggesting that the intact sequence is required to potently inhibit the hα9α10 nAChR. α9α10 nAChRs are expressed not only in the nervous system, but also in a variety of non-neuronal cells, such as cochlear hair cells, keratinocytes, epithelial and immune cells. A potent inhibitor of human α9α10 nAChRs, such as GeXXVIIA, would facilitate unraveling the functions of this nAChR subtype. Furthermore, this unusual nAChR inhibitor may lead to the development of novel α9α10 nAChR-targeting drugs. Full article
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Open AccessArticle Application of Computational Chemical Shift Prediction Techniques to the Cereoanhydride Structure Problem—Carboxylate Complications
Mar. Drugs 2017, 15(6), 171; doi:10.3390/md15060171
Received: 20 March 2017 / Revised: 2 June 2017 / Accepted: 8 June 2017 / Published: 12 June 2017
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Abstract
Despite the vast array of techniques available to modern-day chemists, structural misassignments still occur. These misassignments are often only realized upon attempted synthesis, when the spectra of synthesized products do not match previously reported spectra. This was the case with marine natural product
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Despite the vast array of techniques available to modern-day chemists, structural misassignments still occur. These misassignments are often only realized upon attempted synthesis, when the spectra of synthesized products do not match previously reported spectra. This was the case with marine natural product cereoanhydride. The originally proposed 7-membered ring anhydride (1) was shown to be incorrect, although a likely precursor to the correct structure (2) in both its laboratory synthesis and biosynthesis. Herein, in addition to showing how NMR computations could have been used to arrive at the correct structure, we show that the conversion of 1 to 2 is indeed energetically viable, and we highlight complications in predicting NMR chemical shifts for molecules with acidic protons. Full article
(This article belongs to the Special Issue Structural Techniques in Natural Products Drug Discovery)
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Open AccessArticle Effect of Supercritical Carbon Dioxide Extraction Parameters on the Biological Activities and Metabolites Present in Extracts from Arthrospira platensis
Mar. Drugs 2017, 15(6), 174; doi:10.3390/md15060174
Received: 23 February 2017 / Revised: 8 May 2017 / Accepted: 6 June 2017 / Published: 12 June 2017
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Abstract
Arthrospira platensis was used to obtain functional extracts through supercritical carbon dioxide extraction (SFE-CO2). Pressure (P), temperature (T), co-solvent (CX), static extraction (SX), dispersant (Di) and dynamic extraction (DX) were evaluated as process parameters through a Plackett–Burman design. The maximum extract
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Arthrospira platensis was used to obtain functional extracts through supercritical carbon dioxide extraction (SFE-CO2). Pressure (P), temperature (T), co-solvent (CX), static extraction (SX), dispersant (Di) and dynamic extraction (DX) were evaluated as process parameters through a Plackett–Burman design. The maximum extract yield obtained was 7.48 ± 0.15% w/w. The maximum contents of bioactive metabolites in extracts were 0.69 ± 0.09 µg/g of riboflavin, 5.49 ± 0.10 µg/g of α-tocopherol, 524.46 ± 0.10 µg/g of β-carotene, 1.44 ± 0.10 µg/g of lutein and 32.11 ± 0.12 mg/g of fatty acids with 39.38% of palmitic acid, 20.63% of linoleic acid and 30.27% of γ-linolenic acid. A. platensis extracts had an antioxidant activity of 76.47 ± 0.71 µg GAE/g by Folin–Ciocalteu assay, 0.52 ± 0.02, 0.40 ± 0.01 and 1.47 ± 0.02 µmol TE/g by DPPH, FRAP and TEAC assays, respectively. These extracts showed antimicrobial activity against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231. Overall, co-solvent was the most significant factor for all measured effects (p < 0.05). Arthrospira platensis represents a sustainable source of bioactive compounds through SFE using the following extraction parameters P: 450 bar, CX: 11 g/min, SX: 15 min, DX: 25 min, T: 60 °C and Di: 35 g. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes II, 2017)
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Open AccessArticle A Novel Exopolysaccharide with Metal Adsorption Capacity Produced by a Marine Bacterium Alteromonas sp. JL2810
Mar. Drugs 2017, 15(6), 175; doi:10.3390/md15060175
Received: 29 March 2017 / Revised: 5 June 2017 / Accepted: 9 June 2017 / Published: 12 June 2017
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Abstract
Most marine bacteria can produce exopolysaccharides (EPS). However, very few structures of EPS produced by marine bacteria have been determined. The characterization of EPS structure is important for the elucidation of their biological functions and ecological roles. In this study, the structure of
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Most marine bacteria can produce exopolysaccharides (EPS). However, very few structures of EPS produced by marine bacteria have been determined. The characterization of EPS structure is important for the elucidation of their biological functions and ecological roles. In this study, the structure of EPS produced by a marine bacterium, Alteromonas sp. JL2810, was characterized, and the biosorption of the EPS for heavy metals Cu2+, Ni2+, and Cr6+ was also investigated. Nuclear magnetic resonance (NMR) analysis indicated that the JL2810 EPS have a novel structure consisting of the repeating unit of [-3)-α-Rhap-(1→3)-α-Manp-(1→4)-α-3OAc-GalAp-(1→]. The biosorption of the EPS for heavy metals was affected by a medium pH; the maximum biosorption capacities for Cu2+ and Ni2+ were 140.8 ± 8.2 mg/g and 226.3 ± 3.3 mg/g at pH 5.0; however, for Cr6+ it was 215.2 ± 5.1 mg/g at pH 5.5. Infrared spectrometry analysis demonstrated that the groups of O-H, C=O, and C-O-C were the main function groups for the adsorption of JL2810 EPS with the heavy metals. The adsorption equilibrium of JL2810 EPS for Ni2+ was further analyzed, and the equilibrium data could be better represented by the Langmuir isotherm model. The novel EPS could be potentially used in industrial applications as a novel bio-resource for the removal of heavy metals. Full article
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Open AccessArticle Crellasterones A and B: A-Norsterol Derivatives from the New Caledonian Sponge Crella incrustans
Mar. Drugs 2017, 15(6), 177; doi:10.3390/md15060177
Received: 5 June 2017 / Revised: 10 June 2017 / Accepted: 13 June 2017 / Published: 15 June 2017
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Abstract
Two new steroids, crellasterones A (1) and B (2), together with the previously reported compound chalinasterol (3) and several nucleosides (47), were isolated from the sponge Crella incrustans, collected in New Caledonia.
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Two new steroids, crellasterones A (1) and B (2), together with the previously reported compound chalinasterol (3) and several nucleosides (47), were isolated from the sponge Crella incrustans, collected in New Caledonia. The structures of the new compounds were established by extensive NMR and mass spectroscopic analysis and revealed unprecedented marine natural products with a ring-contracted A-norsterone nucleus and 2-hydroxycyclopentenone chromophore. The absolute configurations were derived from electronic circular dichroism (ECD) measurements in conjunction with high-level density functional theory (DFT) calculations. Full article
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Open AccessArticle Chondroitin Sulfate-Rich Extract of Skate Cartilage Attenuates Lipopolysaccharide-Induced Liver Damage in Mice
Mar. Drugs 2017, 15(6), 178; doi:10.3390/md15060178
Received: 11 May 2017 / Revised: 6 June 2017 / Accepted: 13 June 2017 / Published: 15 June 2017
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Abstract
The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body
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The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body weight (BW) of CS or 400 mg/kg BW of CSE for 3 consecutive days, followed by a one-time intraperitoneal injection of LPS (20 mg/kg BW). The experimental groups were vehicle treatment without LPS injection (NC group), vehicle treatment with LPS injection (LPS group), CS pretreatment with LPS injection (CS group), and CSE pretreatment with LPS injection (CSE group). Hepatic antioxidant enzyme expression levels in the CS and CSE groups were increased relative to those in the LPS group. In LPS-insulted hepatic tissue, inflammatory factors were augmented relative to those in the NC group, but were significantly suppressed by pretreatment with CS or CSE. Moreover, CS and CSE alleviated the LPS-induced apoptotic factors and mitogen-activated protein kinase (MAPK). In addition, CS and CSE effectively decreased the serum lipid concentrations and downregulated hepatic sterol regulatory element-binding proteins expression. In conclusion, the skate CSE could protect against LPS-induced hepatic dyslipidemia, oxidative stress, inflammation, and apoptosis, probably through the regulation of MAPK signaling. Full article
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Open AccessArticle The Roles of Spinochromes in Four Shallow Water Tropical Sea Urchins and Their Potential as Bioactive Pharmacological Agents
Mar. Drugs 2017, 15(6), 179; doi:10.3390/md15060179
Received: 10 May 2017 / Revised: 6 June 2017 / Accepted: 12 June 2017 / Published: 16 June 2017
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Abstract
Spinochromes are principally known to be involved in sea urchin pigmentation as well as for their potentially interesting pharmacological properties. To assess their biological role in sea urchin physiology, experiments are undertaken on crude extracts from four species and on four isolated spinochromes
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Spinochromes are principally known to be involved in sea urchin pigmentation as well as for their potentially interesting pharmacological properties. To assess their biological role in sea urchin physiology, experiments are undertaken on crude extracts from four species and on four isolated spinochromes in order to test their antibacterial, antioxidant, inflammatory and cytotoxic activities. First, the antibacterial assays show that the use of crude extracts as representatives of antibacterial effects of spinochromes are inaccurate. The assays on purified spinochromes showed a decrease in the growth of four strains with an intensity depending on the spinochromes/bacteria system, revealing the participation of spinochromes in the defense system against microorganisms. Secondly, in the 2,2-diphenyl-1-picrylhydrazyl antioxidant assays, spinochromes show an enhanced activity compared to the positive control. This latter observation suggests their involvement in ultraviolet radiation protection. Third, spinochromes present a pro-inflammatory effect on lipopolysaccharide-stimulated macrophages, highlighting their possible implication in the sea urchin immune system. Finally, cytotoxicity assays based on Trypan blue exclusion, performed in view of their possible future applications as drugs, show a weak cytotoxicity of these compounds against human cells. In conclusion, all results confirm the implication of spinochromes in sea urchin defense mechanisms against their external environment and reveal their potential for pharmacological and agronomical industries. Full article
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Open AccessArticle Production of Chitin from Penaeus vannamei By-Products to Pilot Plant Scale Using a Combination of Enzymatic and Chemical Processes and Subsequent Optimization of the Chemical Production of Chitosan by Response Surface Methodology
Mar. Drugs 2017, 15(6), 180; doi:10.3390/md15060180
Received: 12 May 2017 / Revised: 5 June 2017 / Accepted: 9 June 2017 / Published: 16 June 2017
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Abstract
The waste generated from shrimp processing contains valuable materials such as protein, carotenoids, and chitin. The present study describes a process at pilot plant scale to recover chitin from the cephalothorax of Penaeus vannamei using mild conditions. The application of a sequential enzymatic–acid–alkaline
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The waste generated from shrimp processing contains valuable materials such as protein, carotenoids, and chitin. The present study describes a process at pilot plant scale to recover chitin from the cephalothorax of Penaeus vannamei using mild conditions. The application of a sequential enzymatic–acid–alkaline treatment yields 30% chitin of comparable purity to commercial sources. Effluents from the process are rich in protein and astaxanthin, and represent inputs for further by-product recovery. As a last step, chitin is deacetylated to produce chitosan; the optimal conditions are established by applying a response surface methodology (RSM). Under these conditions, deacetylation reaches 92% as determined by Proton Nuclear Magnetic Resonance (1H-NMR), and the molecular weight (Mw) of chitosan is estimated at 82 KDa by gel permeation chromatography (GPC). Chitin and chitosan microstructures are characterized by Scanning Electron Microscopy (SEM). Full article
(This article belongs to the Special Issue Marine Chitin)
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Open AccessArticle How Environmental Factors Affect the Production of Guanidine Alkaloids by the Mediterranean Sponge Crambe crambe
Mar. Drugs 2017, 15(6), 181; doi:10.3390/md15060181
Received: 6 December 2016 / Revised: 2 June 2017 / Accepted: 12 June 2017 / Published: 16 June 2017
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Abstract
Most marine sponges are known to produce a large array of low molecular-weight metabolites which have applications in the pharmaceutical industry. The production of so-called specialized metabolites may be closely related to environmental factors. In this context, assessing the contribution of factors like
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Most marine sponges are known to produce a large array of low molecular-weight metabolites which have applications in the pharmaceutical industry. The production of so-called specialized metabolites may be closely related to environmental factors. In this context, assessing the contribution of factors like temperature, nutrients or light to the metabolomes of sponges provides relevant insights into their chemical ecology as well as the supply issue of natural sponge products. The sponge Crambe crambe was chosen as a model due to its high content of specialized metabolites belonging to polycyclic guanidine alkaloids (PGA). First results were obtained with field data of both wild and farmed specimens collected in two seasons and geographic areas of the North-Western Mediterranean. Then, further insights into factors responsible for changes in the metabolism were gained with sponges cultivated under controlled conditions in an aquarium. Comparative metabolomics showed a clear influence of the seasons and to a lesser extent of the geography while no effect of depth or farming was observed. Interestingly, sponge farming did not limit the production of PGA, while ex situ experiments did not show significant effects of several abiotic factors on the specialized metabolome at a one-month time scale. Some hypotheses were finally proposed to explain the very limited variations of PGA in C. crambe placed under different environmental conditions. Full article
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Open AccessArticle Compositional Characteristics and In Vitro Evaluations of Antioxidant and Neuroprotective Properties of Crude Extracts of Fucoidan Prepared from Compressional Puffing-Pretreated Sargassum crassifolium
Mar. Drugs 2017, 15(6), 183; doi:10.3390/md15060183
Received: 13 May 2017 / Revised: 4 June 2017 / Accepted: 14 June 2017 / Published: 18 June 2017
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Abstract
Fucoidan, a fucose-containing sulfated polysaccharide with diverse biological functions, is mainly recovered from brown algae. In this study, we utilized a compressional-puffing process (CPP) to pretreat Sargassum crassifolium (SC) and extracted fucoidans from SC by warm water. Three fucoidan extracts (SC1: puffing at
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Fucoidan, a fucose-containing sulfated polysaccharide with diverse biological functions, is mainly recovered from brown algae. In this study, we utilized a compressional-puffing process (CPP) to pretreat Sargassum crassifolium (SC) and extracted fucoidans from SC by warm water. Three fucoidan extracts (SC1: puffing at 0 kg/cm2; SC2: puffing at 1.7 kg/cm2; and SC3: puffing at 6.3 kg/cm2) were obtained, and their composition, and antioxidant and neuroprotective activities were examined. The results suggest that CPP decreased the bulk density of algal samples, expanded the algal cellular structures, and eliminated the unpleasant algal odor. The extraction yields of fucoidans were increased and impurities of fucoidans were decreased by increasing the pressures used in CPP. The SC1–SC3 extracts displayed various characteristics of fucoidan as illustrated by the analyses of composition, Fourier transform infrared (FTIR) spectroscopy, and molecular weight. All three extracts SC1–SC3 showed antioxidant activity dose-dependently. Although both SC1 and SC2 possessed high and similar neuronal protective properties, SC2 showed a higher extraction yield, higher efficacy in the reversion of H2O2-induced cytotoxicity in rat pheochromocytoma PC-12 cells, and lower impurities compared with SC1, and thus SC2 is suggested as a good candidate for a therapeutic agent in the preventive treatment of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Nutraceuticals and Functional Foods)
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Open AccessArticle Biotechnological Potential of Cold Adapted Pseudoalteromonas spp. Isolated from ‘Deep Sea’ Sponges
Mar. Drugs 2017, 15(6), 184; doi:10.3390/md15060184
Received: 22 February 2017 / Revised: 9 June 2017 / Accepted: 14 June 2017 / Published: 19 June 2017
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Abstract
The marine genus Pseudoalteromonas is known for its versatile biotechnological potential with respect to the production of antimicrobials and enzymes of industrial interest. We have sequenced the genomes of three Pseudoalteromonas sp. strains isolated from different deep sea sponges on the Illumina MiSeq
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The marine genus Pseudoalteromonas is known for its versatile biotechnological potential with respect to the production of antimicrobials and enzymes of industrial interest. We have sequenced the genomes of three Pseudoalteromonas sp. strains isolated from different deep sea sponges on the Illumina MiSeq platform. The isolates have been screened for various industrially important enzymes and comparative genomics has been applied to investigate potential relationships between the isolates and their host organisms, while comparing them to free-living Pseudoalteromonas spp. from shallow and deep sea environments. The genomes of the sponge associated Pseudoalteromonas strains contained much lower levels of potential eukaryotic-like proteins which are known to be enriched in symbiotic sponge associated microorganisms, than might be expected for true sponge symbionts. While all the Pseudoalteromonas shared a large distinct subset of genes, nonetheless the number of unique and accessory genes is quite large and defines the pan-genome as open. Enzymatic screens indicate that a vast array of enzyme activities is expressed by the isolates, including β-galactosidase, β-glucosidase, and protease activities. A β-glucosidase gene from one of the Pseudoalteromonas isolates, strain EB27 was heterologously expressed in Escherichia coli and, following biochemical characterization, the recombinant enzyme was found to be cold-adapted, thermolabile, halotolerant, and alkaline active. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessArticle The Novel Mechanisms Concerning the Inhibitions of Palmitate-Induced Proinflammatory Factor Releases and Endogenous Cellular Stress with Astaxanthin on MIN6 β-Cells
Mar. Drugs 2017, 15(6), 185; doi:10.3390/md15060185
Received: 15 May 2017 / Revised: 10 June 2017 / Accepted: 14 June 2017 / Published: 20 June 2017
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Abstract
Astaxanthin, an antioxidant agent, can protect pancreatic β-cells of db/db mice from glucotoxicity and resolve chronic inflammation in adipose tissue. Nonetheless, the effects of astaxanthin on free-fatty-acid-induced inflammation and cellular stress in β-cells remain to be demonstrated. Meanwhile, palmitate enhances the secretion of
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Astaxanthin, an antioxidant agent, can protect pancreatic β-cells of db/db mice from glucotoxicity and resolve chronic inflammation in adipose tissue. Nonetheless, the effects of astaxanthin on free-fatty-acid-induced inflammation and cellular stress in β-cells remain to be demonstrated. Meanwhile, palmitate enhances the secretion of pro-inflammatory adipokines monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF120). We therefore investigated the influence of astaxanthin on palmitate-stimulated MCP-1 and VEGF120 secretion in mouse insulinoma (MIN6) pancreatic β-cells. Furthermore, whether astaxanthin prevents cellular stress in MIN6 cells was also assessed. Pre-treatment with astaxanthin or with N-acetyl-cysteine (NAC) which is an antioxidant drug, significantly attenuated the palmitate-induced MCP-1 release through downregulation of phosphorylated c-Jun NH2-terminal protein kinase (JNK) pathways, and suppressed VEGF120 through the PI3K/Akt pathways relative to the cells stimulated with palmitate alone. In addition, palmitate significantly upregulated homologous protein (CHOP) and anti-glucose-regulated protein (GRP78), which are endoplasmic reticulum (ER) stress markers, in MIN6 cells. On the other hand, astaxanthin attenuated the increased CHOP content, but further up-regulated palmitate-stimulated GRP78 protein expression. By contrast, NAC had no effects on either CHOP or GRP78 enhancement induced by palmitate in MIN6 cells. In conclusion, astaxanthin diminishes the palmitate-stimulated increase in MCP-1 secretion via the downregulation of JNK pathways in MIN6 cells, and affects VEGF120 secretion through PI3K/Akt pathways. Moreover, astaxanthin can prevent not only oxidative stress caused endogenously by palmitate but also ER stress, which NAC fails to attenuate, via upregulation of GRP78, an ER chaperon. Full article
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Open AccessArticle Crude Fucoidan Extracts Impair Angiogenesis in Models Relevant for Bone Regeneration and Osteosarcoma via Reduction of VEGF and SDF-1
Mar. Drugs 2017, 15(6), 186; doi:10.3390/md15060186
Received: 12 May 2017 / Revised: 13 June 2017 / Accepted: 16 June 2017 / Published: 20 June 2017
PDF Full-text (4862 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The marine origin polysaccharide fucoidan combines multiple biological activities. As demonstrated by various studies in vitro and in vivo, fucoidans show anti-viral, anti-tumor, anti-oxidant, anti-inflammatory and anti-coagulant properties, although the detailed molecular action remains to be elucidated. The aim of the present study
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The marine origin polysaccharide fucoidan combines multiple biological activities. As demonstrated by various studies in vitro and in vivo, fucoidans show anti-viral, anti-tumor, anti-oxidant, anti-inflammatory and anti-coagulant properties, although the detailed molecular action remains to be elucidated. The aim of the present study is to assess the impact of crude fucoidan extracts, on the formation of vascular structures in co-culture models relevant for bone vascularization during bone repair and for vascularization processes in osteosarcoma. The co-cultures consisted of bone marrow derived mesenchymal stem cells, respectively the osteosarcoma cell line MG63, and human blood derived outgrowth endothelial cells (OEC). The concentration dependent effects on the metabolic activity on endothelial cells and osteoblast cells were first assessed using monocultures of OEC, MSC and MG63 suggesting a concentration of 100 µg/mL as a suitable concentration for further experiments. In co-cultures fucoidan significantly reduced angiogenesis in MSC/OEC but also in MG63/OEC co-cultures suggesting a potential application of fucoidan to lower the vascularization in bone tumors such as osteosarcoma. This was associated with a decrease in VEGF (vascular endothelial growth factor) and SDF-1 (stromal derived factor-1) on the protein level, both related to the control of angiogenesis and furthermore discussed as crucial factors in osteosarcoma progression and metastasis. In terms of bone formation, fucoidan slightly lowered on the calcification process in MSC monocultures and MSC/OEC co-cultures. In summary, these data suggest the suitability of lower fucoidan doses to limit angiogenesis for instance in osteosarcoma. Full article
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Open AccessArticle The Sea Urchin Arbacia lixula: A Novel Natural Source of Astaxanthin
Mar. Drugs 2017, 15(6), 187; doi:10.3390/md15060187
Received: 31 March 2017 / Revised: 8 June 2017 / Accepted: 16 June 2017 / Published: 21 June 2017
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Abstract
Several echinoderms, including sea urchins, are valuable sources of bioactive compounds but their nutraceutical potential is largely unexplored. In fact, the gonads of some sea urchin species contain antioxidants including carotenoids and polyhydroxylated naphthoquinones (PHNQ’s), such as echinochrome A. Astaxanthin is known to
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Several echinoderms, including sea urchins, are valuable sources of bioactive compounds but their nutraceutical potential is largely unexplored. In fact, the gonads of some sea urchin species contain antioxidants including carotenoids and polyhydroxylated naphthoquinones (PHNQ’s), such as echinochrome A. Astaxanthin is known to have particular bioactivity for the prevention of neurodegenerative diseases. This carotenoid is produced by microalgae, while several marine invertebrates can bioaccumulate or synthetize it from metabolic precursors. We determined the carotenoid content and analyzed the bioactivity potential of non-harvested Atlantic-Mediterranean sea urchin Arbacia lixula. The comparison of methanol crude extracts obtained from eggs of farmed and wild specimens revealed a higher bioactivity in farmed individuals fed with a customized fodder. HPLC-analysis revealed a high concentration of astaxanthin (27.0 μg/mg), which was the only pigment observed. This study highlights the potential of farmed A. lixula as a new source of the active stereoisomer of astaxanthin. Full article
(This article belongs to the Special Issue Marine Secondary Metabolite II, 2017)
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Open AccessArticle Effects of Tetrodotoxin in Mouse Models of Visceral Pain
Mar. Drugs 2017, 15(6), 188; doi:10.3390/md15060188
Received: 5 April 2017 / Revised: 7 June 2017 / Accepted: 16 June 2017 / Published: 21 June 2017
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Abstract
Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect
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Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect has been unexplored in visceral pain. Therefore, we tested the effects of systemic TTX in viscero-specific mouse models of chemical stimulation of the colon (intracolonic instillation of capsaicin and mustard oil) and intraperitoneal cyclophosphamide-induced cystitis. The subcutaneous administration of TTX dose-dependently inhibited the number of pain-related behaviors in all evaluated pain models and reversed the referred mechanical hyperalgesia (examined by stimulation of the abdomen with von Frey filaments) induced by capsaicin and cyclophosphamide, but not that induced by mustard oil. Morphine inhibited both pain responses and the referred mechanical hyperalgesia in all tests. Conditional nociceptor‑specific Nav1.7 knockout mice treated with TTX showed the same responses as littermate controls after the administration of the algogens. No motor incoordination after the administration of TTX was observed. These results suggest that blockade of TTX-sensitive sodium channels, but not Nav1.7 subtype alone, by systemic administration of TTX might be a potential therapeutic strategy for the treatment of visceral pain. Full article
(This article belongs to the Special Issue Tetrodotoxin)
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Open AccessArticle Development of a Dunaliella tertiolecta Strain with Increased Zeaxanthin Content Using Random Mutagenesis
Mar. Drugs 2017, 15(6), 189; doi:10.3390/md15060189
Received: 20 February 2017 / Revised: 12 June 2017 / Accepted: 18 June 2017 / Published: 21 June 2017
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Abstract
Zeaxanthin is a xanthophyll pigment that is regarded as one of the best carotenoids for the prevention and treatment of degenerative diseases. In the worldwide natural products market, consumers prefer pigments that have been produced from biological sources. In this study, a Dunaliella
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Zeaxanthin is a xanthophyll pigment that is regarded as one of the best carotenoids for the prevention and treatment of degenerative diseases. In the worldwide natural products market, consumers prefer pigments that have been produced from biological sources. In this study, a Dunaliella tertiolecta strain that has 10–15% higher cellular zeaxanthin content than the parent strain (zea1), was obtained by random mutagenesis using ethyl methanesulfonate (EMS) as a mutagen. This mutant, mp3, was grown under various salinities and light intensities to optimize culture conditions for zeaxanthin production. The highest cellular zeaxanthin content was observed at 1.5 M NaCl and 65–85 μmol photons·m−2·s−1, and the highest daily zeaxanthin productivity was observed at 0.6 M NaCl and 140–160 μmol photons·m−2·s−1. The maximal yield of zeaxanthin from mp3 in fed-batch culture was 8 mg·L−1, which was obtained at 0.6 M NaCl and 140–160 μmol photons·m−2·s−1. These results suggest that random mutagenesis with EMS is useful for generating D. tertiolecta strains with increased zeaxanthin content, and also suggest optimal culture conditions for the enhancement of biomass and zeaxanthin production by the zeaxanthin accumulating mutant strains. Full article
(This article belongs to the Special Issue Marine Microalgae)
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Open AccessArticle The Identification of a SIRT6 Activator from Brown Algae Fucus distichus
Mar. Drugs 2017, 15(6), 190; doi:10.3390/md15060190
Received: 22 May 2017 / Revised: 13 June 2017 / Accepted: 16 June 2017 / Published: 21 June 2017
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Abstract
Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity, although in most cases their mechanisms of action are not understood. In this study, extracts generated from
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Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity, although in most cases their mechanisms of action are not understood. In this study, extracts generated from five brown algae (Fucus dichitus, Fucus vesiculosus (Linnaeus), Cytoseira tamariscofolia, Cytoseira nodacaulis, Alaria esculenta) were tested for their ability to activate SIRT6 resulting in H3K9 deacetylation. Three of the five macroalgal extracts caused a significant increase of H3K9 deacetylation, and the effect was most pronounced for F. dichitus. The compound responsible for this in vitro activity was identified by mass spectrometry as fucoidan. Full article
(This article belongs to the collection Marine Polysaccharides)
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Open AccessArticle Asperentin B, a New Inhibitor of the Protein Tyrosine Phosphatase 1B
Mar. Drugs 2017, 15(6), 191; doi:10.3390/md15060191
Received: 31 January 2017 / Revised: 13 June 2017 / Accepted: 17 June 2017 / Published: 21 June 2017
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Abstract
In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of
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In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillus sydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin. Interestingly, asperentin (2) did not show any inhibition of this enzymatic activity. Asperentin B (1) is discussed as possible therapeutic agents for type 2 diabetes and sleeping sickness. Full article
(This article belongs to the Special Issue Marine Fungal Natural Products)
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Open AccessArticle Cembrene Diterpenoids with Ether Linkages from Sarcophyton ehrenbergi: An Anti-Proliferation and Molecular-Docking Assessment
Mar. Drugs 2017, 15(6), 192; doi:10.3390/md15060192
Received: 3 May 2017 / Revised: 7 June 2017 / Accepted: 14 June 2017 / Published: 21 June 2017
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Abstract
Three new cembrene diterpenoids, sarcoehrenbergilid A–C (13), along with four known diterpenoids, sarcophine (4), (+)-7α,8β-dihydroxydeepoxysarcophine (5), sinulolide A (6), and sinulolide B (7), and one steroid, sardisterol (8), were
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Three new cembrene diterpenoids, sarcoehrenbergilid A–C (13), along with four known diterpenoids, sarcophine (4), (+)-7α,8β-dihydroxydeepoxysarcophine (5), sinulolide A (6), and sinulolide B (7), and one steroid, sardisterol (8), were isolated and characterized from a solvent extract of the Red Sea soft coral Sarcophyton ehrenbergi. Chemical structures were elucidated by NMR and MS analyses with absolute stereochemistry determined by X-ray analysis. Since these isolated cembrene diterpenes contained 10 or more carbons in a large flexible ring, conformer stabilities were examined based on density functional theory calculations. Anti-proliferative activities for 18 were evaluated against three human tumor cell lines of different origins including the: lung (A549), colon (Caco-2), and liver (HepG2). Sardisterol (8) was the most potent of the metabolites isolated with an IC50 of 27.3 µM against the A549 cell line. Since an elevated human-cancer occurrence is associated with an aberrant receptor function for the epidermal growth factor receptor (EGFR), molecular docking studies were used to examine preferential metabolite interactions/binding and probe the mode-of-action for metabolite-anti tumor activity. Full article
(This article belongs to the collection Marine Compounds and Cancer) Printed Edition available
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Review

Jump to: Research

Open AccessFeature PaperReview The Rising Tide of Antimicrobial Resistance in Aquaculture: Sources, Sinks and Solutions
Mar. Drugs 2017, 15(6), 158; doi:10.3390/md15060158
Received: 31 March 2017 / Revised: 22 May 2017 / Accepted: 25 May 2017 / Published: 1 June 2017
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Abstract
As the human population increases there is an increasing reliance on aquaculture to supply a safe, reliable, and economic supply of food. Although food production is essential for a healthy population, an increasing threat to global human health is antimicrobial resistance. Extensive antibiotic
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As the human population increases there is an increasing reliance on aquaculture to supply a safe, reliable, and economic supply of food. Although food production is essential for a healthy population, an increasing threat to global human health is antimicrobial resistance. Extensive antibiotic resistant strains are now being detected; the spread of these strains could greatly reduce medical treatment options available and increase deaths from previously curable infections. Antibiotic resistance is widespread due in part to clinical overuse and misuse; however, the natural processes of horizontal gene transfer and mutation events that allow genetic exchange within microbial populations have been ongoing since ancient times. By their nature, aquaculture systems contain high numbers of diverse bacteria, which exist in combination with the current and past use of antibiotics, probiotics, prebiotics, and other treatment regimens—singularly or in combination. These systems have been designated as “genetic hotspots” for gene transfer. As our reliance on aquaculture grows, it is essential that we identify the sources and sinks of antimicrobial resistance, and monitor and analyse the transfer of antimicrobial resistance between the microbial community, the environment, and the farmed product, in order to better understand the implications to human and environmental health. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessReview Cyanobacterial Toxins of the Laurentian Great Lakes, Their Toxicological Effects, and Numerical Limits in Drinking Water
Mar. Drugs 2017, 15(6), 160; doi:10.3390/md15060160
Received: 17 March 2017 / Revised: 22 April 2017 / Accepted: 2 May 2017 / Published: 2 June 2017
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Abstract
Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. Seasonally, they dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic
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Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. Seasonally, they dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic lakes is attributed to a variety of unique adaptations including N and P concentrating mechanisms, N2 fixation, colony formation that inhibits predation, vertical movement via gas vesicles, and the production of toxic or otherwise bioactive molecules. While some of these molecules have been explored for their medicinal benefits, others are potent toxins harmful to humans, animals, and other wildlife known as cyanotoxins. In humans these cyanotoxins affect various tissues, including the liver, central and peripheral nervous system, kidneys, and reproductive organs among others. They induce acute effects at low doses in the parts-per-billion range and some are tumor promoters linked to chronic diseases such as liver and colorectal cancer. The occurrence of cyanoHABs and cyanotoxins in lakes presents challenges for maintaining safe recreational aquatic environments and the production of potable drinking water. CyanoHABs are a growing problem in the North American (Laurentian) Great Lakes basin. This review summarizes information on the occurrence of cyanoHABs in the Great Lakes, toxicological effects of cyanotoxins, and appropriate numerical limits on cyanotoxins in finished drinking water. Full article
(This article belongs to the Special Issue Harmful Marine Phytoplankton)
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Open AccessReview Interpreting Microbial Biosynthesis in the Genomic Age: Biological and Practical Considerations
Mar. Drugs 2017, 15(6), 165; doi:10.3390/md15060165
Received: 28 April 2017 / Revised: 22 May 2017 / Accepted: 31 May 2017 / Published: 6 June 2017
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Abstract
Genome mining has become an increasingly powerful, scalable, and economically accessible tool for the study of natural product biosynthesis and drug discovery. However, there remain important biological and practical problems that can complicate or obscure biosynthetic analysis in genomic and metagenomic sequencing projects.
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Genome mining has become an increasingly powerful, scalable, and economically accessible tool for the study of natural product biosynthesis and drug discovery. However, there remain important biological and practical problems that can complicate or obscure biosynthetic analysis in genomic and metagenomic sequencing projects. Here, we focus on limitations of available technology as well as computational and experimental strategies to overcome them. We review the unique challenges and approaches in the study of symbiotic and uncultured systems, as well as those associated with biosynthetic gene cluster (BGC) assembly and product prediction. Finally, to explore sequencing parameters that affect the recovery and contiguity of large and repetitive BGCs assembled de novo, we simulate Illumina and PacBio sequencing of the Salinispora tropica genome focusing on assembly of the salinilactam (slm) BGC. Full article
(This article belongs to the Special Issue Connecting Marine Microbial Natural Products to Biosynthetic Pathways)
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Open AccessReview The Understanding of the Metazoan Skeletal System, Based on the Initial Discoveries with Siliceous and Calcareous Sponges
Mar. Drugs 2017, 15(6), 172; doi:10.3390/md15060172
Received: 31 March 2017 / Revised: 3 June 2017 / Accepted: 8 June 2017 / Published: 12 June 2017
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Abstract
Initiated by studies on the mechanism of formation of the skeletons of the evolutionary oldest still extant multicellular animals, the sponges (phylum Porifera) have provided new insights into the mechanism of formation of the Ca-phosphate/hydroxyapatite skeleton of vertebrate bone. Studies on the formation
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Initiated by studies on the mechanism of formation of the skeletons of the evolutionary oldest still extant multicellular animals, the sponges (phylum Porifera) have provided new insights into the mechanism of formation of the Ca-phosphate/hydroxyapatite skeleton of vertebrate bone. Studies on the formation of the biomineral skeleton of sponges revealed that both the formation of the inorganic siliceous skeletons (sponges of the class of Hexactinellida and Demospongiae) and of the calcareous skeletons (class of Calcarea) is mediated by enzymes (silicatein: polymerization of biosilica; and carbonic anhydrase: deposition of Ca-carbonate). Detailed studies of the initial mineralization steps in human bone-forming cells showed that this process is also controlled by enzymes, starting with the deposition of Ca-carbonate bio-seeds, mediated by carbonic anhydrases-II and -IX, followed by non-enzymatic transformation of the formed amorphous Ca-carbonate deposits into amorphous Ca-phosphate and finally hydroxyapatite crystals. The required phosphate is provided by enzymatic (alkaline phosphatase-mediated) degradation of an inorganic polymer, polyphosphate (polyP), which also acts as a donor for chemically useful energy in this process. These new discoveries allow the development of novel biomimetic strategies for treatment of bone diseases and defects. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessReview Marine Sponges and Bacteria as Challenging Sources of Enzyme Inhibitors for Pharmacological Applications
Mar. Drugs 2017, 15(6), 173; doi:10.3390/md15060173
Received: 5 May 2017 / Revised: 6 June 2017 / Accepted: 8 June 2017 / Published: 12 June 2017
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Abstract
Enzymes play key roles in different cellular processes, for example, in signal transduction, cell differentiation and proliferation, metabolic processes, DNA damage repair, apoptosis, and response to stress. A deregulation of enzymes has been considered one of the first causes of several diseases, including
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Enzymes play key roles in different cellular processes, for example, in signal transduction, cell differentiation and proliferation, metabolic processes, DNA damage repair, apoptosis, and response to stress. A deregulation of enzymes has been considered one of the first causes of several diseases, including cancers. In the last several years, enzyme inhibitors, being good candidates as drugs in the pathogenic processes, have received an increasing amount of attention for their potential application in pharmacology. The marine environment is considered a challenging source of enzyme inhibitors for pharmacological applications. In this review, we report on secondary metabolites with enzyme inhibitory activity, focusing our attention on marine sponges and bacteria as promising sources. In the case of sponges, we only reported the kinase inhibitors, because this class was the most representative isolated so far from these marine organisms. Full article
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Open AccessReview Off the Shelf Fouling Management
Mar. Drugs 2017, 15(6), 176; doi:10.3390/md15060176
Received: 6 May 2017 / Revised: 31 May 2017 / Accepted: 8 June 2017 / Published: 14 June 2017
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Abstract
This chapter tells the story of a research thread that identified and modified a pharmaceutical that could be a component of environmentally benign fouling management coatings. First, I present the background context of biofouling and how fouling is managed. The major target of
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This chapter tells the story of a research thread that identified and modified a pharmaceutical that could be a component of environmentally benign fouling management coatings. First, I present the background context of biofouling and how fouling is managed. The major target of the research is disrupting transduction of a complex process in all macrofouling organisms: metamorphosis. Using a bioassay directed approach we first identified a pharmaceutical candidate. Then, based on structure function studies coupled with laboratory and field bioassays, we simplified the molecule, eliminating halogens and aromatic rings to a pharmacophore that could be readily broken down by bacteria. Next, we did further structure function studies coupled to lab and field bioassays of modifications that enabled delivery of the molecule in a variety of coatings. The outcome is a different way of thinking about managing fouling and concepts in which molecules are designed to perform a function and then degrade. This work is discussed in the context of existing fouling management approaches and business models which use long-lived broad-spectrum biocides which have consequences for human, environmental health, and food security. Full article
(This article belongs to the Special Issue Antifouling Marine Natural Products)
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Open AccessReview Microbial Diseases of Bivalve Mollusks: Infections, Immunology and Antimicrobial Defense
Mar. Drugs 2017, 15(6), 182; doi:10.3390/md15060182
Received: 16 January 2017 / Revised: 8 June 2017 / Accepted: 8 June 2017 / Published: 17 June 2017
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Abstract
A variety of bivalve mollusks (phylum Mollusca, class Bivalvia) constitute a prominent commodity in fisheries and aquacultures, but are also crucial in order to preserve our ecosystem’s complexity and function. Bivalve mollusks, such as clams, mussels, oysters and scallops, are relevant bred species,
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A variety of bivalve mollusks (phylum Mollusca, class Bivalvia) constitute a prominent commodity in fisheries and aquacultures, but are also crucial in order to preserve our ecosystem’s complexity and function. Bivalve mollusks, such as clams, mussels, oysters and scallops, are relevant bred species, and their global farming maintains a high incremental annual growth rate, representing a considerable proportion of the overall fishery activities. Bivalve mollusks are filter feeders; therefore by filtering a great quantity of water, they may bioaccumulate in their tissues a high number of microorganisms that can be considered infectious for humans and higher vertebrates. Moreover, since some pathogens are also able to infect bivalve mollusks, they are a threat for the entire mollusk farming industry. In consideration of the leading role in aquaculture and the growing financial importance of bivalve farming, much interest has been recently devoted to investigate the pathogenesis of infectious diseases of these mollusks in order to be prepared for public health emergencies and to avoid dreadful income losses. Several bacterial and viral pathogens will be described herein. Despite the minor complexity of the organization of the immune system of bivalves, compared to mammalian immune systems, a precise description of the different mechanisms that induce its activation and functioning is still missing. In the present review, a substantial consideration will be devoted in outlining the immune responses of bivalves and their repertoire of immune cells. Finally, we will focus on the description of antimicrobial peptides that have been identified and characterized in bivalve mollusks. Their structural and antimicrobial features are also of great interest for the biotechnology sector as antimicrobial templates to combat the increasing antibiotic-resistance of different pathogenic bacteria that plague the human population all over the world. Full article
(This article belongs to the Special Issue Marine Proteins and Peptides)
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