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Mar. Drugs, Volume 16, Issue 1 (January 2018)

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Cover Story (view full-size image) Aaptos is a genus of marine sponge which belongs to Suberitidae and distributed in the tropical and [...] Read more.
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Editorial

Jump to: Research, Review

Open AccessEditorial Acknowledgement to Reviewers of Marine Drugs in 2017
Mar. Drugs 2018, 16(1), 35; doi:10.3390/md16010035
Received: 17 January 2018 / Accepted: 17 January 2018 / Published: 17 January 2018
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Abstract
Peer review is an essential part in the publication process, ensuring that Marine Drugs maintains high quality standards for its published papers.[...] Full article

Research

Jump to: Editorial, Review

Open AccessArticle The Suppressive Activity of Fucofuroeckol-A Derived from Brown Algal Ecklonia stolonifera Okamura on UVB-Induced Mast Cell Degranulation
Mar. Drugs 2018, 16(1), 1; doi:10.3390/md16010001
Received: 14 October 2017 / Revised: 12 November 2017 / Accepted: 5 December 2017 / Published: 4 January 2018
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Abstract
UV light, especially UVB, is known as a trigger of allergic reaction, leading to mast cell degranulation and histamine release. In this study, phlorotannin Fucofuroeckol-A (F-A) derived from brown algal Ecklonia stolonifera Okamura was evaluated for its protective capability against UVB-induced allergic reaction
[...] Read more.
UV light, especially UVB, is known as a trigger of allergic reaction, leading to mast cell degranulation and histamine release. In this study, phlorotannin Fucofuroeckol-A (F-A) derived from brown algal Ecklonia stolonifera Okamura was evaluated for its protective capability against UVB-induced allergic reaction in RBL-2H3 mast cells. It was revealed that F-A significantly suppress mast cell degranulation via decreasing histamine release as well as intracellular Ca2+ elevation at the concentration of 50 μM. Moreover, the inhibitory effect of F-A on IL-1β and TNF-α productions was also evidenced. Notably, the protective activity of F-A against mast cell degranulation was found due to scavenging ROS production. Accordingly, F-A from brown algal E. stolonifera was suggested to be promising candidate for its protective capability against UVB-induced allergic reaction. Full article
(This article belongs to the Special Issue Anti-Photoagaing and Photo-Protective Compounds from Marine Organisms)
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Open AccessArticle Topical Application of Glycolipids from Isochrysis galbana Prevents Epidermal Hyperplasia in Mice
Mar. Drugs 2018, 16(1), 2; doi:10.3390/md16010002
Received: 25 November 2017 / Revised: 6 December 2017 / Accepted: 7 December 2017 / Published: 25 December 2017
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Abstract
Chronic inflammatory skin diseases such as psoriasis have a significant impact on society. Currently, the major topical treatments have many side effects, making their continued use in patients difficult. Microalgae have emerged as a source of bio-active molecules such as glycolipids with potent
[...] Read more.
Chronic inflammatory skin diseases such as psoriasis have a significant impact on society. Currently, the major topical treatments have many side effects, making their continued use in patients difficult. Microalgae have emerged as a source of bio-active molecules such as glycolipids with potent anti-inflammatory properties. We aimed to investigate the effects of a glycolipid (MGMG-A) and a glycolipid fraction (MGDG) obtained from the microalga Isochrysis galbana on a TPA-induced epidermal hyperplasia murine model. In a first set of experiments, we examined the preventive effects of MGMG-A and MGDG dissolved in acetone on TPA-induced hyperplasia model in mice. In a second step, we performed an in vivo permeability study by using rhodamine-containing cream, ointment, or gel to determinate the formulation that preserves the skin architecture and reaches deeper. The selected formulation was assayed to ensure the stability and enhanced permeation properties of the samples in an ex vivo experiment. Finally, MGDG-containing cream was assessed in the hyperplasia murine model. The results showed that pre-treatment with acetone-dissolved glycolipids reduced skin edema, epidermal thickness, and pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6, IL-17) in epidermal tissue. The in vivo and ex vivo permeation studies showed that the cream formulation had the best permeability profile. In the same way, MGDG-cream formulation showed better permeation than acetone-dissolved preparation. MGDG-cream application attenuated TPA-induced skin edema, improved histopathological features, and showed a reduction of the inflammatory cell infiltrate. In addition, this formulation inhibited epidermal expression of COX-2 in a similar way to dexamethasone. Our results suggest that an MGDG-containing cream could be an emerging therapeutic strategy for the treatment of inflammatory skin pathologies such as psoriasis. Full article
(This article belongs to the Special Issue Marine Anti-inflammatory Agents)
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Open AccessArticle Marine Cryptophytes Are Great Sources of EPA and DHA
Mar. Drugs 2018, 16(1), 3; doi:10.3390/md16010003
Received: 23 November 2017 / Revised: 15 December 2017 / Accepted: 18 December 2017 / Published: 26 December 2017
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Abstract
Microalgae have the ability to synthetize many compounds, some of which have been recognized as a source of functional ingredients for nutraceuticals with positive health effects. One well-known example is the long-chain polyunsaturated fatty acids (PUFAs), which are essential for human nutrition. Eicosapentaenoic
[...] Read more.
Microalgae have the ability to synthetize many compounds, some of which have been recognized as a source of functional ingredients for nutraceuticals with positive health effects. One well-known example is the long-chain polyunsaturated fatty acids (PUFAs), which are essential for human nutrition. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the two most important long-chain omega-3 (ω-3) PUFAs involved in human physiology, and both industries are almost exclusively based on microalgae. In addition, algae produce phytosterols that reduce serum cholesterol. Here we determined the growth rates, biomass yields, PUFA and sterol content, and daily gain of eight strains of marine cryptophytes. The maximal growth rates of the cryptophytes varied between 0.34–0.70 divisions day−1, which is relatively good in relation to previously screened algal taxa. The studied cryptophytes were extremely rich in ω-3 PUFAs, especially in EPA and DHA (range 5.8–12.5 and 0.8–6.1 µg mg dry weight−1, respectively), but their sterol concentrations were low. Among the studied strains, Storeatula major was superior in PUFA production, and it also produces all PUFAs, i.e., α-linolenic acid (ALA), stearidonic acid (SDA), EPA, and DHA, which is rare in phytoplankton in general. We conclude that marine cryptophytes are a good alternative for the ecologically sustainable and profitable production of health-promoting lipids. Full article
(This article belongs to the Special Issue The Sources and Production of Polyunsaturated Fatty Acids)
Open AccessArticle Characterization of a Long-Lived Alginate Lyase Derived from Shewanella Species YH1
Mar. Drugs 2018, 16(1), 4; doi:10.3390/md16010004
Received: 7 November 2017 / Revised: 11 December 2017 / Accepted: 13 December 2017 / Published: 27 December 2017
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Abstract
Polysaccharides from seaweeds are widely used in various fields, including the food, biomedical material, cosmetic, and biofuel industries. Alginate, which is a major polysaccharide in brown algae, and the products of its degradation (oligosaccharides) have been used in stabilizers, thickeners, and gelling agents,
[...] Read more.
Polysaccharides from seaweeds are widely used in various fields, including the food, biomedical material, cosmetic, and biofuel industries. Alginate, which is a major polysaccharide in brown algae, and the products of its degradation (oligosaccharides) have been used in stabilizers, thickeners, and gelling agents, especially in the food industry. Discovering novel alginate lyases with unique characteristics for the efficient production of oligosaccharides may be relevant for the food and pharmaceutical fields. In this study, we identified a unique alginate lyase derived from an alginate-utilizing bacterium, Shewanella species YH1. The recombinant enzyme (rAlgSV1-PL7) was produced in an Escherichia coli system and it was classified in the Polysaccharide Lyase family 7. The optimal temperature and pH for rAlgSV1-PL7 activity were around 45 °C and 8, respectively. Interestingly, we observed that rAlgSV1-PL7 retained over 80% of its enzyme activity after incubation at 30 °C for at least 20 days, indicating that rAlgSV1-PL7 is a long-lived enzyme. Moreover, the degradation of alginate by rAlgSV1-PL7 produced one to four sugars because of the broad substrate specificity of this enzyme. Our findings suggest that rAlgSV1-PL7 may represent a new commercially useful enzyme. Full article
(This article belongs to the Special Issue Marine Oligosaccharides and Polysaccharides)
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Open AccessArticle Pinnatifidenyne-Derived Ethynyl Oxirane Acetogenins from Laurencia viridis
Mar. Drugs 2018, 16(1), 5; doi:10.3390/md16010005
Received: 2 October 2017 / Revised: 5 December 2017 / Accepted: 13 December 2017 / Published: 29 December 2017
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Abstract
Red algae of Laurencia continue to provide wide structural diversity and complexity of halogenated C15 acetogenin medium-ring ethers. Here, we described the isolation of three new C15 acetogenins (35), and one truncated derivative (6) from
[...] Read more.
Red algae of Laurencia continue to provide wide structural diversity and complexity of halogenated C15 acetogenin medium-ring ethers. Here, we described the isolation of three new C15 acetogenins (35), and one truncated derivative (6) from Laurencia viridis collected on the Canary Islands. These compounds are interesting variations on the pinnatifidenyne structure that included the first examples of ethynyl oxirane derivatives (34). The structures were elucidated by extensive study of NMR (Nuclear Magnetic Resonance) data, J-based configuration analysis and DFT (Density Functional Theory) calculations. Their antiproliferative activity against six human solid tumor cell lines was evaluated. Full article
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Open AccessArticle Toxicology of Gambierdiscus spp. (Dinophyceae) from Tropical and Temperate Australian Waters
Mar. Drugs 2018, 16(1), 7; doi:10.3390/md16010007
Received: 19 October 2017 / Revised: 7 December 2017 / Accepted: 15 December 2017 / Published: 1 January 2018
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Abstract
Ciguatera Fish Poisoning (CFP) is a human illness caused by the consumption of marine fish contaminated with ciguatoxins (CTX) and possibly maitotoxins (MTX), produced by species from the benthic dinoflagellate genus Gambierdiscus. Here, we describe the identity and toxicology of Gambierdiscus spp.
[...] Read more.
Ciguatera Fish Poisoning (CFP) is a human illness caused by the consumption of marine fish contaminated with ciguatoxins (CTX) and possibly maitotoxins (MTX), produced by species from the benthic dinoflagellate genus Gambierdiscus. Here, we describe the identity and toxicology of Gambierdiscus spp. isolated from the tropical and temperate waters of eastern Australia. Based on newly cultured strains, we found that four Gambierdiscus species were present at the tropical location, including G. carpenteri, G. lapillus and two others which were not genetically identical to other currently described species within the genus, and may represent new species. Only G. carpenteri was identified from the temperate location. Using LC-MS/MS analysis we did not find any characterized microalgal CTXs (P-CTX-3B, P-CTX-3C, P-CTX-4A and P-CTX-4B) or MTX-1; however, putative maitotoxin-3 (MTX-3) was detected in all species except for the temperate population of G. carpenteri. Using the Ca2+ influx SH-SY5Y cell Fluorescent Imaging Plate Reader (FLIPR) bioassay we found CTX-like activity in extracts of the unidentified Gambierdiscus strains and trace level activity in strains of G. lapillus. While no detectable CTX-like activity was observed in tropical or temperate strains of G. carpenteri, all species showed strong maitotoxin-like activity. This study, which represents the most comprehensive analyses of the toxicology of Gambierdiscus strains isolated from Australia to date, suggests that CFP in this region may be caused by currently undescribed ciguatoxins and maitotoxins. Full article
(This article belongs to the Special Issue Algal Toxins II, 2017)
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Open AccessArticle MSP-4, an Antimicrobial Peptide, Induces Apoptosis via Activation of Extrinsic Fas/FasL- and Intrinsic Mitochondria-Mediated Pathways in One Osteosarcoma Cell Line
Mar. Drugs 2018, 16(1), 8; doi:10.3390/md16010008
Received: 31 October 2017 / Revised: 5 December 2017 / Accepted: 12 December 2017 / Published: 2 January 2018
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Abstract
Osteosarcoma (OS) is a common malignant bone cancer. The relatively high density of a person’s bone structure means low permeability for drugs, and so finding drugs that can be more effective is important and should not be delayed. MSPs are marine antimicrobial peptides
[...] Read more.
Osteosarcoma (OS) is a common malignant bone cancer. The relatively high density of a person’s bone structure means low permeability for drugs, and so finding drugs that can be more effective is important and should not be delayed. MSPs are marine antimicrobial peptides (AMP) and natural compounds extracted from Nile tilapia (Oreochromis niloticus). MSP-4 is a part of the AMPs series, with the advantage of having a molecular weight of about 2.7-kDa and anticancer effects, although the responsible anticancer mechanism is not very clear. The goal of this study is to determine the workings of the mechanism associated with apoptosis resulting from MSP-4 in osteosarcoma MG63 cells. The study showed that MSP-4 significantly induced apoptosis in MG63 cells, with Western blot indicating that MSP-4 induced this apoptosis through an intrinsic pathway and an extrinsic pathway. Thus, a pretreatment system with a particular inhibitor of Z-IETD-FMK (caspase-8 inhibitor) and Z-LEHD-FMK (caspase-9 inhibitor) significantly attenuated the cleavage of caspase-3 and prevented apoptosis. These observations indicate that low concentrations of MSP-4 can help induce the apoptosis of MG63 through a Fas/FasL- and mitochondria-mediated pathway and suggest a potentially innovative alternative to the treatment of human osteosarcoma. Full article
(This article belongs to the Special Issue Connection of Marine Natural Products and Cell Apoptosis)
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Open AccessArticle Bromopyrrole Alkaloids with the Inhibitory Effects against the Biofilm Formation of Gram Negative Bacteria
Mar. Drugs 2018, 16(1), 9; doi:10.3390/md16010009
Received: 27 September 2017 / Revised: 27 November 2017 / Accepted: 11 December 2017 / Published: 2 January 2018
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Abstract
Anti-biofilm assay guided fractionation of the marine sponge Stylissa massa revealed the butanol soluble fraction that was possessing the inhibitory activity toward the biofilm formation of bacterium E. coli. Chromatographic separation of the bioactive fraction resulted in the isolation of 32 bromopyrrole
[...] Read more.
Anti-biofilm assay guided fractionation of the marine sponge Stylissa massa revealed the butanol soluble fraction that was possessing the inhibitory activity toward the biofilm formation of bacterium E. coli. Chromatographic separation of the bioactive fraction resulted in the isolation of 32 bromopyrrole alkaloids, including six new alkaloids, named stylisines A–F (16). The structures of new alkaloids were established by comprehensive analyses of the two-dimensional (2D) NMR (COSY, HMQC, and HMBC) and the high resolution electrospray ionization mass spectroscopy (HRESIMS) data, while the absolute configurations were determined by the X-ray diffraction and the electronic circular dichroism (ECD) data. Bioassay results indicated that phakellin-based alkaloids, including dibromoisophakellin and dibromophakellin, significantly reduced the biofilm formation of the bacterium E. coli. Present work provided a group of new natural scaffolds for the inhibitory effects against the biofilm formation of E. coli. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
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Open AccessArticle Eicosanoid Diversity of Stony Corals
Mar. Drugs 2018, 16(1), 10; doi:10.3390/md16010010
Received: 9 November 2017 / Revised: 13 December 2017 / Accepted: 20 December 2017 / Published: 3 January 2018
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Abstract
Oxylipins are well-established lipid mediators in plants and animals. In mammals, arachidonic acid (AA)-derived eicosanoids control inflammation, fever, blood coagulation, pain perception and labor, and, accordingly, are used as drugs, while lipoxygenases (LOX), as well as cyclooxygenases (COX) serve as therapeutic targets for
[...] Read more.
Oxylipins are well-established lipid mediators in plants and animals. In mammals, arachidonic acid (AA)-derived eicosanoids control inflammation, fever, blood coagulation, pain perception and labor, and, accordingly, are used as drugs, while lipoxygenases (LOX), as well as cyclooxygenases (COX) serve as therapeutic targets for drug development. In soft corals, eicosanoids are synthesized on demand from AA by LOX, COX, and catalase-related allene oxide synthase-lipoxygenase (cAOS-LOX) and hydroperoxide lyase-lipoxygenase (cHPL-LOX) fusion proteins. Reef-building stony corals are used as model organisms for the stress-related genomic studies of corals. Yet, the eicosanoid synthesis capability and AA-derived lipid mediator profiles of stony corals have not been determined. In the current study, the genomic and transcriptomic data about stony coral LOXs, AOS-LOXs, and COXs were analyzed and the eicosanoid profiles and AA metabolites of three stony corals, Acropora millepora, A. cervicornis, and Galaxea fascicularis, were determined by reverse-phase high-performance liquid chromatography (RP-HPLC) coupled with MS-MS and a radiometric detector. Our results confirm that the active LOX and AOS-LOX pathways are present in Acropora sp., which correspond to the genomic/sequence data reported earlier. In addition, LOX, AOS-LOX, and COX products were detected in the closely related species G. fascicularis. In conclusion, the functional 8R-LOX and/or AOS-LOX pathways are abundant among corals, while COXs are restricted to certain soft and stony coral lineages. Full article
(This article belongs to the Special Issue Marine Small-Molecule Bioactive Agents and Therapeutic Targets)
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Open AccessArticle Formation of Silver Nanoparticles Using Fluorescence Properties of Chitosan Oligomers
Mar. Drugs 2018, 16(1), 11; doi:10.3390/md16010011
Received: 31 October 2017 / Revised: 5 December 2017 / Accepted: 14 December 2017 / Published: 3 January 2018
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Abstract
In this study, silver chloride nanoparticles (AgCl NPs) were prepared using chitosan oligomer (CHI) and chitosan oligomer derivatives (CHI-FITC). The CHI and CHI-FITC were used as markers to confirm the formation of AgCl NPs using their fluorescence properties as well as stabilizers. The
[...] Read more.
In this study, silver chloride nanoparticles (AgCl NPs) were prepared using chitosan oligomer (CHI) and chitosan oligomer derivatives (CHI-FITC). The CHI and CHI-FITC were used as markers to confirm the formation of AgCl NPs using their fluorescence properties as well as stabilizers. The fluorescence properties of CHI and CHI-FITC were monitored by a luminescence spectrophotometer, and the morphology of the AgCl NPs was further confirmed by transmission electron microscopy (TEM) and X-ray diffraction (XRD). The fluorescence of CHI and CHI-FITC was quenched by the formation of AgCl NPs, and the Stern–Volmer equation was used to compare the two types of stabilizer. The CHI and CHI-FITC stabilizer were linear and nonlinear, respectively, with respect to the Stern–Volmer equation, and considered to be usable as fluorescence indicators to confirm the formation behavior of AgCl NPs through fluorescence quenching. Full article
(This article belongs to the Special Issue Marine Oligosaccharides and Polysaccharides)
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Open AccessArticle Functional Expression and Characterization of the Recombinant N-Acetyl-Glucosamine/N-Acetyl-Galactosamine-Specific Marine Algal Lectin BPL3
Mar. Drugs 2018, 16(1), 13; doi:10.3390/md16010013
Received: 28 November 2017 / Revised: 16 December 2017 / Accepted: 28 December 2017 / Published: 5 January 2018
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Abstract
Lectins, characterized by their carbohydrate-binding ability, have extensive practical applications. However, their industrial use is limited due to impurity. Thus, quality-controlled production of recombinant lectin is necessary. In this study, the algal lectin BPL3 (Bryopsis plumosa lectin 3) was successfully produced using
[...] Read more.
Lectins, characterized by their carbohydrate-binding ability, have extensive practical applications. However, their industrial use is limited due to impurity. Thus, quality-controlled production of recombinant lectin is necessary. In this study, the algal lectin BPL3 (Bryopsis plumosa lectin 3) was successfully produced using a bacterial expression system, BL21(DE3), with an artificial repeated structure (dimeric construct). Recombinant dimeric BPL3 (rD2BPL3) was confirmed by LC-MS/MS spectrometry. Expression efficiency was greater for the construct with the repeat structure (rD2BPL3) than the monomeric form (rD1BPL3). Optimal conditions for expression were 1 mM IPTG at 20 °C. Recombinant lectin was purified under denaturing conditions and refolded by the flash dilution method. Recombinant BPL3 was solubilized in 1× PBS containing 2 M urea. rD2BPL3 showed strong hemagglutination activity using human erythrocyte. rD2BPL3 had a similar sugar specificity to that of the native protein, i.e., to N-acetyl-glucosamine (GlcNAc) and N-acetyl-galactosamine (GalNAc). Glycan array results showed that recombinant BPL3 and native BPL3 exhibited different binding properties. Both showed weak binding activity to α-Man-Sp. Native BPL3 showed strong binding specificity to the alpha conformation of amino sugars, and rD2BPL3 had binding activity to the beta conformation. The process developed in this study was suitable for the quality-controlled large-scale production of recombinant lectins. Full article
(This article belongs to the Special Issue Marine Drugs Interact with Functional Proteins)
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Open AccessArticle Suppression of RANKL-Induced Osteoclastogenesis by the Metabolites from the Marine Fungus Aspergillus flocculosus Isolated from a Sponge Stylissa sp.
Mar. Drugs 2018, 16(1), 14; doi:10.3390/md16010014
Received: 3 November 2017 / Revised: 29 November 2017 / Accepted: 8 December 2017 / Published: 5 January 2018
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Abstract
A new α-pyrone merosesquiterpenoid possessing an angular tetracyclic carbon skeleton, ochraceopone F (1), and four known secondary metabolites, aspertetranone D (2), cycloechinulin (3), wasabidienone E (4), and mactanamide (5), were isolated from the
[...] Read more.
A new α-pyrone merosesquiterpenoid possessing an angular tetracyclic carbon skeleton, ochraceopone F (1), and four known secondary metabolites, aspertetranone D (2), cycloechinulin (3), wasabidienone E (4), and mactanamide (5), were isolated from the marine fungus Aspergillus flocculosus derived from a sponge Stylissa sp. collected in Vietnam. The structures of Compounds 15 were elucidated by analysis of 1D and 2D NMR spectra and MS data. All the isolated compounds were evaluated for anti-proliferation activity and their suppression effects on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation using tartate-resisant acid phosphatase (TRAP). Compounds 15 had no anti-proliferative effect on human cancer cell lines up to 30 μg/mL. Among these compounds, aspertetranone D (2) and wasabidienone E (4) exhibited weak osteoclast differentiation inhibitory activity at 10 μg/mL. However, mactanamide (5) showed a potent suppression effect of osteoclast differentiation without any evidence of cytotoxicity. Full article
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Open AccessArticle Aquaculture Soft Coral Lobophytum crassum as a Producer of Anti-Proliferative Cembranoids
Mar. Drugs 2018, 16(1), 15; doi:10.3390/md16010015
Received: 22 November 2017 / Revised: 14 December 2017 / Accepted: 19 December 2017 / Published: 7 January 2018
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Abstract
Our continuous search for marine bioactive secondary metabolites led to the screening of crude extracts from a variety of aquaculture soft corals. The ethyl acetate (EtOAc) extract of Lobophytum crassum showed a distinctive chemical profile that was different from the wild type. It
[...] Read more.
Our continuous search for marine bioactive secondary metabolites led to the screening of crude extracts from a variety of aquaculture soft corals. The ethyl acetate (EtOAc) extract of Lobophytum crassum showed a distinctive chemical profile that was different from the wild type. It demonstrated significant anti-proliferative activity against Molt 4 leukemia cell with an IC50 value of 1 μg/mL after 24 h. Chemical investigation focusing on the unique peaks in L. crassum profile led to the discovery of a new α-tocopherol crassumtocopherol C (1), and two new cembrane-based diterpenoids culobophylins D (2) and E (3), along with ten known cembranoids (413). The structures of these isolates were elucidated using extensive spectroscopic techniques and a comparison with previously published data of related metabolites. Compound 2 was found to possess the first identified saturated internal C4-O-C14 linkage six-membered ring among all cembrane-type diterpenoids. The anti-proliferative activity of all the isolates (except 3) was evaluated against a limited panel of leukemia cell lines (Molt 4, K562, U937, and Sup-T1). The major compounds 8 and 10 exhibited the most anti-proliferative potent effect, with IC50 values ranging from 1.2 to 7.1 μM. The Structure Activity Relationship (SAR) of the isolates suggested that the presence of lactone moieties is crucial for the anti-proliferative activity against leukemia cells. Our work indicated that the development of an efficient aquaculture protocols for soft corals led to the discovery of new secondary metabolites with unique structural features. Such protocols can lead to a sustainable supply of biologically active compounds in enough quantities for the pharmaceutical industry. Full article
(This article belongs to the Special Issue Natural Products from Coral Reef Organisms)
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Open AccessArticle Effect of Low Molecular Weight Oligopeptides Isolated from Sea Cucumber on Diabetic Wound Healing in db/db Mice
Mar. Drugs 2018, 16(1), 16; doi:10.3390/md16010016
Received: 20 October 2017 / Revised: 28 December 2017 / Accepted: 28 December 2017 / Published: 8 January 2018
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Abstract
Impaired wound healing is a major clinical problem in patients with diabetes and is the leading cause of lower limb amputation. This study is aimed to observe the effects of small molecule oligopeptides isolated from sea cucumber (SCCOPs) on the wound healing process
[...] Read more.
Impaired wound healing is a major clinical problem in patients with diabetes and is the leading cause of lower limb amputation. This study is aimed to observe the effects of small molecule oligopeptides isolated from sea cucumber (SCCOPs) on the wound healing process in diabetic mice. Ninety db/db male mice were divided into five groups, including the model control group, whey protein group (0.50 g/kg) and three SCCOPs dose groups (0.25 g/kg, 0.50 g/kg and 1.00 g/kg). Additionally, 18 db/m male mice were used as normal control group. After full-thickness incisions on the dorsum, mice in SCCOPs-treated groups were intragastrically administered SCCOPs, while others were administered vehicle or whey protein. Mice were sacrificed on days 4, 7 and 14. The wound healing condition, inflammatory response, angiogenesis, collagen deposition, oxidative stress and nutritional status were evaluated. A pathological report showed increased vascularisation, collagen deposition and epithelialisation in SCCOPs-treated groups. SCCOPs-treated mice showed decreased C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, chemokine (C-C motif) ligand 2 (CCL2) and reactive oxygen species (ROS) contents, and increased IL-10, stromal cell-derived factor-1 alpha (SDF-1α), nitric oxide (NO), albumin (ALB), prealbumin (PA) and transferrin (TRF) levels and vascular endothelial growth factor (VEGF) expression. All parameters were significant (p < 0.05) in comparison to model control group. These results suggest that treatment with SCCOPs can promote significant wound healing in diabetic mice. Full article
(This article belongs to the Special Issue Nutraceuticals and Functional Foods)
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Open AccessCommunication Difference in Uptake of Tetrodotoxin and Saxitoxins into Liver Tissue Slices among Pufferfish, Boxfish and Porcupinefish
Mar. Drugs 2018, 16(1), 17; doi:10.3390/md16010017
Received: 9 December 2017 / Revised: 27 December 2017 / Accepted: 4 January 2018 / Published: 8 January 2018
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Abstract
Although pufferfish of the family Tetraodontidae contain high levels of tetrodotoxin (TTX) mainly in the liver, some species of pufferfish, boxfish of the family Ostraciidae, and porcupinefish of the family Diodontidae do not. To clarify the mechanisms, uptake of TTX and saxitoxins (STXs)
[...] Read more.
Although pufferfish of the family Tetraodontidae contain high levels of tetrodotoxin (TTX) mainly in the liver, some species of pufferfish, boxfish of the family Ostraciidae, and porcupinefish of the family Diodontidae do not. To clarify the mechanisms, uptake of TTX and saxitoxins (STXs) into liver tissue slices of pufferfish, boxfish and porcupinefish was examined. Liver tissue slices of the pufferfish (toxic species Takifugu rubripes and non-toxic species Lagocephalus spadiceus, L. cheesemanii and Sphoeroides pachygaster) incubated with 50 µM TTX accumulated TTX (0.99–1.55 µg TTX/mg protein) after 8 h, regardless of the toxicity of the species. In contrast, in liver tissue slices of boxfish (Ostracion immaculatus) and porcupinefish (Diodon holocanthus, D. liturosus, D. hystrix and Chilomycterus reticulatus), TTX content did not increase with incubation time, and was about 0.1 µg TTX/mg protein. When liver tissue slices were incubated with 50 µM STXs for 8 h, the STXs content was <0.1 µg STXs/mg protein, irrespective of the fish species. These findings indicate that, like the toxic species of pufferfish T. rubripes, non-toxic species such as L. spadiceus, L. cheesemanii and S. pachygaster, potentially take up TTX into the liver, while non-toxic boxfish and porcupinefish do not take up either TTX or STXs. Full article
(This article belongs to the Special Issue Tetrodotoxin)
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Open AccessArticle Isoaaptamine Induces T-47D Cells Apoptosis and Autophagy via Oxidative Stress
Mar. Drugs 2018, 16(1), 18; doi:10.3390/md16010018
Received: 6 December 2017 / Revised: 22 December 2017 / Accepted: 4 January 2018 / Published: 9 January 2018
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Abstract
Aaptos is a genus of marine sponge which belongs to Suberitidae and is distributed in tropical and subtropical oceans. Bioactivity-guided fractionation of Aaptos sp. methanolic extract resulted in the isolation of aaptamine, demethyloxyaaptamine, and isoaaptamine. The cytotoxic activity of the isolated compounds was
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Aaptos is a genus of marine sponge which belongs to Suberitidae and is distributed in tropical and subtropical oceans. Bioactivity-guided fractionation of Aaptos sp. methanolic extract resulted in the isolation of aaptamine, demethyloxyaaptamine, and isoaaptamine. The cytotoxic activity of the isolated compounds was evaluated revealing that isoaaptamine exhibited potent cytotoxic activity against breast cancer T-47D cells. In a concentration-dependent manner, isoaaptamine inhibited the growth of T-47D cells as indicated by short-(MTT) and long-term (colony formation) anti-proliferative assays. The cytotoxic effect of isoaaptamine was mediated through apoptosis as indicated by DNA ladder formation, caspase-7 activation, XIAP inhibition and PARP cleavage. Transmission electron microscopy and flow cytometric analysis using acridine orange dye indicated that isoaaptamine treatment could induce T-47D cells autophagy. Immunoblot assays demonstrated that isoaaptamine treatment significantly activated autophagy marker proteins such as type II LC-3. In addition, isoaaptamine treatment enhanced the activation of DNA damage (γH2AX) and ER stress-related proteins (IRE1 α and BiP). Moreover, the use of isoaaptamine resulted in a significant increase in the generation of reactive oxygen species (ROS) as well as in the disruption of mitochondrial membrane potential (MMP). The pretreatment of T-47D cells with an ROS scavenger, N-acetyl-l-cysteine (NAC), attenuated the apoptosis and MMP disruption induced by isoaaptamine up to 90%, and these effects were mediated by the disruption of nuclear factor erythroid 2-related factor 2 (Nrf 2)/p62 pathway. Taken together, these findings suggested that the cytotoxic effect of isoaaptamine is associated with the induction of apoptosis and autophagy through oxidative stress. Our data indicated that isoaaptamine represents an interesting drug lead in the war against breast cancer. Full article
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Open AccessArticle The Bioactive Extract of Pinnigorgia sp. Induces Apoptosis of Hepatic Stellate Cells via ROS-ERK/JNK-Caspase-3 Signaling
Mar. Drugs 2018, 16(1), 19; doi:10.3390/md16010019
Received: 4 December 2017 / Revised: 30 December 2017 / Accepted: 6 January 2018 / Published: 9 January 2018
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Abstract
The activation of hepatic stellate cells (HSCs) is a significant phenomenon during the pathogenesis of liver disorders, including liver cirrhosis and fibrosis. Here, we identified that the extract from a gorgonian coral Pinnigorgia sp. (Pin) induced apoptosis of HSC-T6 cells. Pin inhibited the
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The activation of hepatic stellate cells (HSCs) is a significant phenomenon during the pathogenesis of liver disorders, including liver cirrhosis and fibrosis. Here, we identified that the extract from a gorgonian coral Pinnigorgia sp. (Pin) induced apoptosis of HSC-T6 cells. Pin inhibited the viability of HSC-T6 cells and increased their subG1 population, DNA fragmentation, caspase-3 activation, and reactive oxygen species (ROS) production in a concentration-dependent manner. The Pin-induced ROS generation and apoptotic effects were significantly reversed by a thiol antioxidant, N-acetylcysteine (NAC). Additionally, Pin induced ERK/JNK phosphorylation and pharmacological inhibition of ERK/JNK rescued the Pin-induced cell death. Pin-activated ERK/JNK were significantly reduced after the administration of NAC; however, the inhibition of ERK/JNK failed to change the Pin-induced ROS production. Similarly, pinnigorgiol A, a pure compound isolated from Pin, elicited ROS production and apoptosis in HSC-T6 cells. The pinnigorgiol A-induced apoptosis was retrained by NAC. Together, it appears that Pin leads to apoptosis in HSC-T6 cells through ROS-mediated ERK/JNK signaling and caspase-3 activation. Pinnigorgiol A serves as a bioactive compound of Pin and may exhibit therapeutic potential by clearance of HSCs. Full article
(This article belongs to the Special Issue Development and Application of Herbal Medicine from Marine Origin)
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Open AccessArticle Posidonia oceanica (L.) Delile Ethanolic Extract Modulates Cell Activities with Skin Health Applications
Mar. Drugs 2018, 16(1), 21; doi:10.3390/md16010021
Received: 6 November 2017 / Revised: 14 December 2017 / Accepted: 8 January 2018 / Published: 10 January 2018
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Abstract
Seagrasses are high plants sharing adaptive metabolic features with both terrestrial plants and marine algae, resulting in a phytocomplex possibly endowed with interesting biological properties. The aim of this study is to evaluate the in vitro activities on skin cells of an ethanolic
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Seagrasses are high plants sharing adaptive metabolic features with both terrestrial plants and marine algae, resulting in a phytocomplex possibly endowed with interesting biological properties. The aim of this study is to evaluate the in vitro activities on skin cells of an ethanolic extract obtained from the leaves of Posidonia oceanica (L.) Delile, family Potamogetonaceae, herein named Posidonia ethanolic extract (PEE). PEE showed high radical scavenging activity, high phenolic content, and resulted rich in chicoric acid, as determined through HPLC-MS analysis. The use of MTT assay on fibroblasts showed a PEE cytotoxicity threshold (IC05) of 50 µg/mL at 48 h, while a sub-toxic dose of 20 µg/mL induced a significant increase of fibroblast growth rate after 10 days. In addition, an ELISA assay revealed that PEE doses of 5 and 10 µg/mL induced collagen production in fibroblasts. PEE induced dose-dependent mushroom tyrosinase inhibition, up to about 45% inhibition at 1000 µg/mL, while 50% reduction of melanin was observed in melanoma cells exposed to 50 µg/mL PEE. Finally, PEE lipolytic activity was assessed by measuring glycerol release from adipocytes following triglyceride degradation. In conclusion, we have collected new data about the biological activities of the phytocomplex of P. oceanica seagrass on skin cells. Our findings indicate that PEE could be profitably used in the development of products for skin aging, undesired hyperpigmentation, and cellulite. Full article
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Open AccessArticle Bacillibactin and Bacillomycin Analogues with Cytotoxicities against Human Cancer Cell Lines from Marine Bacillus sp. PKU-MA00093 and PKU-MA00092
Mar. Drugs 2018, 16(1), 22; doi:10.3390/md16010022
Received: 27 November 2017 / Revised: 21 December 2017 / Accepted: 5 January 2018 / Published: 10 January 2018
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Abstract
Nonribosomal peptides from marine Bacillus strains have received considerable attention for their complex structures and potent bioactivities. In this study, we carried out PCR-based genome mining for potential nonribosomal peptides producers from our marine bacterial library. Twenty-one “positive” strains were screened out from
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Nonribosomal peptides from marine Bacillus strains have received considerable attention for their complex structures and potent bioactivities. In this study, we carried out PCR-based genome mining for potential nonribosomal peptides producers from our marine bacterial library. Twenty-one “positive” strains were screened out from 180 marine bacterial strains, and subsequent small-scale fermentation, HPLC and phylogenetic analysis afforded Bacillus sp. PKU-MA00092 and PKU-MA00093 as two candidates for large-scale fermentation and isolation. Ten nonribosomal peptides, including four bacillibactin analogues (14) and six bacillomycin D analogues (510) were discovered from Bacillus sp. PKU-MA00093 and PKU-MA00092, respectively. Compounds 1 and 2 are two new compounds and the 1H NMR and 13C NMR data of compounds 7 and 9 is first provided. All compounds 110 were assayed for their cytotoxicities against human cancer cell lines HepG2 and MCF7, and the bacillomycin D analogues 710 showed moderate cytotoxicities with IC50 values from 2.9 ± 0.1 to 8.2 ± 0.2 µM. The discovery of 510 with different fatty acid moieties gave us the opportunity to reveal the structure-activity relationships of bacillomycin analogues against these human cancer cell lines. These results enrich the structural diversity and bioactivity properties of nonribosomal peptides from marine Bacillus strains. Full article
(This article belongs to the Special Issue Genome Mining and Marine Microbial Natural Products)
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Open AccessArticle Nanocomposite of Half-Fin Anchovy Hydrolysates/Zinc Oxide Nanoparticles Exhibits Actual Non-Toxicity and Regulates Intestinal Microbiota, Short-Chain Fatty Acids Production and Oxidative Status in Mice
Mar. Drugs 2018, 16(1), 23; doi:10.3390/md16010023
Received: 15 December 2017 / Revised: 29 December 2017 / Accepted: 4 January 2018 / Published: 11 January 2018
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Abstract
The nanocomposite of half-fin anchovy hydrolysates (HAHp) and zinc oxide nanoparticles (ZnO NPs) (named as HAHp(3.0)/ZnO NPs) demonstrated increased antibacterial activity compared to either HAHp(3.0) or ZnO NPs as per our previous studies. Also, reactive oxygen species (ROS) formation was detected in Escherichia
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The nanocomposite of half-fin anchovy hydrolysates (HAHp) and zinc oxide nanoparticles (ZnO NPs) (named as HAHp(3.0)/ZnO NPs) demonstrated increased antibacterial activity compared to either HAHp(3.0) or ZnO NPs as per our previous studies. Also, reactive oxygen species (ROS) formation was detected in Escherichia coli cells after treatment with HAHp(3.0)/ZnO NPs. The aim of the present study was to evaluate the acute toxicity of this nanocomposite and to investigate its effect on intestinal microbiota composition, short-chain fatty acids (SCFAs) production, and oxidative status in healthy mice. The limit test studies show that this nanoparticle is non-toxic at the doses tested. The administration of HAHp(3.0)/ZnO NPs, daily dose of 1.0 g/kg body weight for 14 days, increased the number of goblet cells in jejunum. High-throughput 16S ribosomal RNA gene sequencing of fecal samples revealed that HAHp(3.0)/ZnO NPs increased Firmicutes and reduced Bacteriodetes abundances in female mice. Furthermore, the microbiota for probiotic-type bacteria, including Lactobacillus and Bifidobacterium, and SCFAs-producing bacteria in the Clostridia class, e.g., Lachnospiraceae_unclassified and Lachnospiraceae_UCG-001, were enriched in the feces of female mice. Increases of SCFAs, especially statistically increased propionic and butyric acids, indicated the up-regulated anti-inflammatory activity of HAHp(3.0)/ZnO NPs. Additionally, some positive responses in liver, like markedly increased glutathione and decreased malonaldehyde contents, indicated the improved oxidative status. Therefore, our results suggest that HAHp(3.0)/ZnO NPs could have potential applications as a safe regulator of intestinal microbiota or also can be used as an antioxidant used in food products. Full article
(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)
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Open AccessArticle Antibacterial and Antioxidant Capacities and Attenuation of Lipid Accumulation in 3T3-L1 Adipocytes by Low-Molecular-Weight Fucoidans Prepared from Compressional-Puffing-Pretreated Sargassum Crassifolium
Mar. Drugs 2018, 16(1), 24; doi:10.3390/md16010024
Received: 21 November 2017 / Revised: 20 December 2017 / Accepted: 4 January 2018 / Published: 11 January 2018
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Abstract
In this study, we extracted fucoidan from compressional-puffing-pretreated Sargassum crassifolium by hot water. The crude extract of fucoidan (SC) was degraded by various degradation reagents and four low-molecular-weight (LMW) fucoidans, namely SCO (degradation by hydrogen peroxide), SCA (degradation by ascorbic acid), SCOA (degradation
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In this study, we extracted fucoidan from compressional-puffing-pretreated Sargassum crassifolium by hot water. The crude extract of fucoidan (SC) was degraded by various degradation reagents and four low-molecular-weight (LMW) fucoidans, namely SCO (degradation by hydrogen peroxide), SCA (degradation by ascorbic acid), SCOA (degradation by hydrogen peroxide + ascorbic acid), and SCH (degradation by hydrogen chloride) were obtained. The degradation reagents studied could effectively degrade fucoidan into LMW fucoidans, as revealed by intrinsic viscosity, agarose gel electrophoresis, and molecular weight analyses. These LMW fucoidans had higher uronic acid content and sulfate content than those of SC. It was found that SCOA exhibited antibacterial activity. All LMW fucoidans showed antioxidant activities as revealed by DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt), and FRAP (ferric reducing antioxidant power) methods. Biological experiments showed that SC and SCOA had relatively high activity for the reversal of H2O2-induced cell death in 3T3-L1 adipocytes, and SCOA showed the highest effect on attenuation of lipid accumulation in 3T3-L1 adipocytes. Therefore, for the LMW fucoidans tested, SCOA showed antibacterial activity and had a high fucose content, high sulfate content, high activity for the reversal of H2O2-induced cell death, and a marked effect on attenuation of lipid accumulation. It can thus be recommended as a natural and safe antibacterial and anti-adipogenic agent for food, cosmetic, and nutraceutical applications. Full article
(This article belongs to the Special Issue Nutraceuticals and Functional Foods)
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Open AccessArticle Lipid-Lowering Polyketides from the Fungus Penicillium Steckii HDN13-279
Mar. Drugs 2018, 16(1), 25; doi:10.3390/md16010025
Received: 2 November 2017 / Revised: 2 December 2017 / Accepted: 8 January 2018 / Published: 12 January 2018
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Abstract
Seven new polyketides, named tanzawaic acids R–X (16, 11), along with seven known analogues (710 and 1214), were isolated from Penicillium steckii HDN13-279. Their structures, including the absolute configurations, were elucidated by
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Seven new polyketides, named tanzawaic acids R–X (16, 11), along with seven known analogues (710 and 1214), were isolated from Penicillium steckii HDN13-279. Their structures, including the absolute configurations, were elucidated by NMR, MS, X-ray diffraction, circular dichroism (CD) analyses and chemical derivatization. Five compounds (2, 3, 6, 10 and 12) significantly decreased the oleic acid (OA)-elicited lipid accumulation in HepG2 liver cells at the concentration of 10 μM, among which, four compounds (3, 6, 10 and 12) significantly decreased intracellular total cholesterol (TC) levels and three Compounds (3, 6, and 10) significantly decreased intracellular triglyceride (TG) levels. Moreover, the TG-lowering capacities of compounds 6 and 10 were comparable with those of simvastatin, with the TG levels being nearly equal to blank control. This is the first report on the lipid-lowering activity of tanzawaic acid derivatives. Full article
(This article belongs to the Special Issue Marine Drugs in the Management of Metabolic Diseases)
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Open AccessArticle Evaluation of Rapid, Early Warning Approaches to Track Shellfish Toxins Associated with Dinophysis and Alexandrium Blooms
Mar. Drugs 2018, 16(1), 28; doi:10.3390/md16010028
Received: 13 October 2017 / Revised: 20 December 2017 / Accepted: 6 January 2018 / Published: 13 January 2018
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Abstract
Marine biotoxin-contaminated seafood has caused thousands of poisonings worldwide this century. Given these threats, there is an increasing need for improved technologies that can be easily integrated into coastal monitoring programs. This study evaluates approaches for monitoring toxins associated with recurrent toxin-producing Alexandrium
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Marine biotoxin-contaminated seafood has caused thousands of poisonings worldwide this century. Given these threats, there is an increasing need for improved technologies that can be easily integrated into coastal monitoring programs. This study evaluates approaches for monitoring toxins associated with recurrent toxin-producing Alexandrium and Dinophysis blooms on Long Island, NY, USA, which cause paralytic and diarrhetic shellfish poisoning (PSP and DSP), respectively. Within contrasting locations, the dynamics of pelagic Alexandrium and Dinophysis cell densities, toxins in plankton, and toxins in deployed blue mussels (Mytilus edulis) were compared with passive solid-phase adsorption toxin tracking (SPATT) samplers filled with two types of resin, HP20 and XAD-2. Multiple species of wild shellfish were also collected during Dinophysis blooms and used to compare toxin content using two different extraction techniques (single dispersive and double exhaustive) and two different toxin analysis assays (liquid chromatography/mass spectrometry and the protein phosphatase inhibition assay (PP2A)) for the measurement of DSP toxins. DSP toxins measured in the HP20 resin were significantly correlated (R2 = 0.7–0.9, p < 0.001) with total DSP toxins in shellfish, but were detected more than three weeks prior to detection in deployed mussels. Both resins adsorbed measurable levels of PSP toxins, but neither quantitatively tracked Alexandrium cell densities, toxicity in plankton or toxins in shellfish. DSP extraction and toxin analysis methods did not differ significantly (p > 0.05), were highly correlated (R2 = 0.98–0.99; p < 0.001) and provided complete recovery of DSP toxins from standard reference materials. Blue mussels (Mytilus edulis) and ribbed mussels (Geukensia demissa) were found to accumulate DSP toxins above federal and international standards (160 ng g−1) during Dinophysis blooms while Eastern oysters (Crassostrea virginica) and soft shell clams (Mya arenaria) did not. This study demonstrated that SPATT samplers using HP20 resin coupled with PP2A technology could be used to provide early warning of DSP, but not PSP, events for shellfish management. Full article
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Open AccessArticle Optimization of Extraction Conditions and Characterization of Pepsin-Solubilised Collagen from Skin of Giant Croaker (Nibea japonica)
Mar. Drugs 2018, 16(1), 29; doi:10.3390/md16010029
Received: 27 December 2017 / Revised: 6 January 2018 / Accepted: 10 January 2018 / Published: 14 January 2018
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Abstract
In the present study, response surface methodology was performed to investigate the effects of extraction parameters on pepsin-solubilised collagen (PSC) from the skin of the giant croaker Nibea japonica. The optimum extraction conditions of PSC were as follows: concentration of pepsin was
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In the present study, response surface methodology was performed to investigate the effects of extraction parameters on pepsin-solubilised collagen (PSC) from the skin of the giant croaker Nibea japonica. The optimum extraction conditions of PSC were as follows: concentration of pepsin was 1389 U/g, solid-liquid ratio was 1:57 and hydrolysis time was 8.67 h. Under these conditions, the extraction yield of PSC was up to 84.85%, which is well agreement with the predict value of 85.03%. The PSC from Nibea japonica skin was then characterized as type I collagen by using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The fourier transforms infrared spetroscopy (FTIR) analysis revealed that PSC maintains its triple-helical structure by the hydrogen bond. All PSCs were soluble in the pH range of 1.0–4.0 and decreases in solubility were observed at neutral or alkaline conditions. All PSCs had a decrease in solubility in the presence of sodium chloride, especially with a concentration above 2%. So, the Nibea japonica skin could serve as another potential source of collagen. Full article
(This article belongs to the Special Issue Collagen from Marine Biological Source and Medical Applications)
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Open AccessArticle Characterization of a Novel Alginate Lyase from Marine Bacterium Vibrio furnissii H1
Mar. Drugs 2018, 16(1), 30; doi:10.3390/md16010030
Received: 6 December 2017 / Revised: 20 December 2017 / Accepted: 11 January 2018 / Published: 15 January 2018
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Abstract
Alginate lyases show great potential for industrial and medicinal applications, especially as an attractive biocatalyst for the production of oligosaccharides with special bioactivities. A novel alginate lyase, AlyH1, from the marine bacterium Vibrio furnissii H1, which has been newly isolated from rotten seaweed,
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Alginate lyases show great potential for industrial and medicinal applications, especially as an attractive biocatalyst for the production of oligosaccharides with special bioactivities. A novel alginate lyase, AlyH1, from the marine bacterium Vibrio furnissii H1, which has been newly isolated from rotten seaweed, was purified and characterized. The purified enzyme showed the specific activity of 2.40 U/mg. Its molecular mass was 35.8 kDa. The optimal temperature and pH were 40 °C and pH 7.5, respectively. AlyH1 maintained stability at neutral pH (7.0–8.0) and temperatures below 30 °C. Metal ions Na+, Mg2+, and K+ increased the activity of the enzyme. With sodium alginate as the substrate, the Km and Vmax values of AlyH1 were 2.28 mg/mL and 2.81 U/mg, respectively. AlyH1 exhibited activities towards both polyguluronate and polymannuronate, and preferentially degraded polyguluronate. Products prepared from sodium alginate by AlyH1 were displayed to be di-, tri-, and tetra-alginate oligosaccharides. A partial amino acid sequence (190 aa) of AlyH1 analysis suggested that AlyH1 was an alginate lyase of polysaccharide lyase family 7. The sequence showed less than 77% identity to the reported alginate lyases. These data demonstrated that AlyH1 could be as a novel and potential candidate in application of alginate oligosaccharides production with low polymerization degrees. Full article
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Open AccessArticle Specific Molecular Signatures for Type II Crustins in Penaeid Shrimp Uncovered by the Identification of Crustin-Like Antimicrobial Peptides in Litopenaeus vannamei
Mar. Drugs 2018, 16(1), 31; doi:10.3390/md16010031
Received: 30 August 2017 / Revised: 23 September 2017 / Accepted: 16 October 2017 / Published: 16 January 2018
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Abstract
Crustins form a large family of antimicrobial peptides (AMPs) in crustaceans composed of four sub-groups (Types I-IV). Type II crustins (Type IIa or “Crustins” and Type IIb or “Crustin-like”) possess a typical hydrophobic N-terminal region and are by far the most representative sub-group
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Crustins form a large family of antimicrobial peptides (AMPs) in crustaceans composed of four sub-groups (Types I-IV). Type II crustins (Type IIa or “Crustins” and Type IIb or “Crustin-like”) possess a typical hydrophobic N-terminal region and are by far the most representative sub-group found in penaeid shrimp. To gain insight into the molecular diversity of Type II crustins in penaeids, we identified and characterized a Type IIb crustin in Litopenaeus vannamei (Crustin-like Lv) and compared Type II crustins at both molecular and transcriptional levels. Although L. vannamei Type II crustins (Crustin Lv and Crustin-like Lv) are encoded by separate genes, they showed a similar tissue distribution (hemocytes and gills) and transcriptional response to the shrimp pathogens Vibrio harveyi and White spot syndrome virus (WSSV). As Crustin Lv, Crustin-like Lv transcripts were found to be present early in development, suggesting a maternal contribution to shrimp progeny. Altogether, our in silico and transcriptional data allowed to conclude that (1) each sub-type displays a specific amino acid signature at the C-terminal end holding both the cysteine-rich region and the whey acidic protein (WAP) domain, and that (2) shrimp Type II crustins evolved from a common ancestral gene that conserved a similar pattern of transcriptional regulation. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
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Open AccessArticle Low Molecular Weight Chitosan-Insulin Complexes Solubilized in a Mixture of Self-Assembled Labrosol and Plurol Oleaque and Their Glucose Reduction Activity in Rats
Mar. Drugs 2018, 16(1), 32; doi:10.3390/md16010032
Received: 10 December 2017 / Revised: 4 January 2018 / Accepted: 10 January 2018 / Published: 16 January 2018
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Abstract
Oral insulin delivery that better mimics physiological pathways is a necessity as it ensures patient comfort and compliance. A system which is based on a vehicle of nano order where positively charged chitosan interacts with negatively charged insulin and forms a polyelectrolyte complex
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Oral insulin delivery that better mimics physiological pathways is a necessity as it ensures patient comfort and compliance. A system which is based on a vehicle of nano order where positively charged chitosan interacts with negatively charged insulin and forms a polyelectrolyte complex (PEC) solubilizate, which is then solubilized into an oily phase of oleic acid, labrasol, and plurol oleaque-protects insulin against enzymatic gastrointestinal reduction. The use of an anionic fatty acid in the oily phase, such as oleic acid, is thought to allow an interaction with cationic chitosan, hence reducing particle size. Formulations were assessed based on their hypoglycaemic capacities in diabetic rats as compared to conventional subcutaneous dosage forms. 50 IU/kg oral insulin strength could only induce blood glucose reduction equivalent to that of 5 IU/kg (1 International unit = 0.0347 mg of human insulin). Parameters that influence the pharmacological availability were evaluated. A preliminary investigation of the mechanism of absorption suggests the involvement of the lymphatic route. Full article
(This article belongs to the Special Issue Marine Chitin)
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Open AccessArticle A Rapid Method for the Determination of Fucoxanthin in Diatom
Mar. Drugs 2018, 16(1), 33; doi:10.3390/md16010033
Received: 4 December 2017 / Revised: 4 January 2018 / Accepted: 6 January 2018 / Published: 22 January 2018
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Abstract
Fucoxanthin is a natural pigment found in microalgae, especially diatoms and Chrysophyta. Recently, it has been shown to have anti-inflammatory, anti-tumor, and anti-obesityactivity in humans. Phaeodactylum tricornutum is a diatom with high economic potential due to its high content of fucoxanthin and
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Fucoxanthin is a natural pigment found in microalgae, especially diatoms and Chrysophyta. Recently, it has been shown to have anti-inflammatory, anti-tumor, and anti-obesityactivity in humans. Phaeodactylum tricornutum is a diatom with high economic potential due to its high content of fucoxanthin and eicosapentaenoic acid. In order to improve fucoxanthin production, physical and chemical mutagenesis could be applied to generate mutants. An accurate and rapid method to assess the fucoxanthin content is a prerequisite for a high-throughput screen of mutants. In this work, the content of fucoxanthin in P. tricornutum was determined using spectrophotometry instead of high performance liquid chromatography (HPLC). This spectrophotometric method is easier and faster than liquid chromatography and the standard error was less than 5% when compared to the HPLC results. Also, this method can be applied to other diatoms, with standard errors of 3–14.6%. It provides a high throughput screening method for microalgae strains producing fucoxanthin. Full article
(This article belongs to the collection Marine Carotenoids)
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Open AccessArticle Microbial Degradation Behavior in Seawater of Polyester Blends Containing Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)
Mar. Drugs 2018, 16(1), 34; doi:10.3390/md16010034
Received: 29 November 2017 / Revised: 9 January 2018 / Accepted: 15 January 2018 / Published: 17 January 2018
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Abstract
The microbial degradation behavior of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and its compound with several polyesters such as poly(butylene adipate-co-telephtharate) (PBAT), poly(butylene succinate) (PBS), and polylactic acid (PLA) in seawater was tested by a biological oxygen demand (BOD) method. PHBHHx showed excellent
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The microbial degradation behavior of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and its compound with several polyesters such as poly(butylene adipate-co-telephtharate) (PBAT), poly(butylene succinate) (PBS), and polylactic acid (PLA) in seawater was tested by a biological oxygen demand (BOD) method. PHBHHx showed excellent biodegradation in seawater in this study. In addition, the biodegradation rate of several blends was much influenced by the weight ratio of PHBHHx in their blends and decreased in accordance with the decrement of PHBHHX ratio. The surface morphology of the sheet was important factor for controlling the biodegradation rate of PHBHHx-containing blends in seawater. Full article
(This article belongs to the Special Issue Marine Biodegradable Polymers)
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Open AccessArticle Anti-Phytopathogenic and Cytotoxic Activities of Crude Extracts and Secondary Metabolites of Marine-Derived Fungi
Mar. Drugs 2018, 16(1), 36; doi:10.3390/md16010036
Received: 30 November 2017 / Revised: 8 January 2018 / Accepted: 15 January 2018 / Published: 18 January 2018
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Abstract
Thirty-one isolates belonging to eight genera in seven orders were identified from 141 strains that were isolated from several marine plants. Alternaria sp. and Fusarium sp. were found to be the predominant fungi. Evaluation of the anti-phytopathogenic bacterial and fungal activities, as well
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Thirty-one isolates belonging to eight genera in seven orders were identified from 141 strains that were isolated from several marine plants. Alternaria sp. and Fusarium sp. were found to be the predominant fungi. Evaluation of the anti-phytopathogenic bacterial and fungal activities, as well as the cytotoxicity of these 31 extracts, revealed that most of them displayed different levels of bioactivities. Due to their interesting bioactivities, two fungal strains—Fusarium equiseti (P18) and Alternaria sp. (P8)—were selected for chemical investigation and compounds 14 were obtained. The structure of 1 was elucidated by 1D and 2D NMR analysis, as well as high-resolution electrospray ionization mass spectroscopy (HRESIMS), and the absolute configuration of its stereogenic carbon (C-11) was established by comparison of the experimental and calculated electronic circular-dichroism (ECD) spectra. Moreover, alterperylenol (4) exhibited antibacterial activity against Clavibacter michiganensis with a minimum inhibitory concentration (MIC) of 1.95 μg/mL, which was 2-fold stronger than that of streptomycin sulfate. Additionally, an antibacterial mechanism study revealed that 4 caused membrane hyperpolarization without evidence of destruction of cell membrane integrity. Furthermore, stemphyperylenol (3) displayed potent antifungal activity against Pestallozzia theae and Alternaria brassicicola with MIC values equal to those of carbendazim. The cytotoxicity of 1 and 2 against human lung carcinoma (A-549), human cervical carcinoma (HeLa), and human hepatoma (HepG2) cell lines were also evaluated. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes II, 2017)
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Open AccessArticle TTX-Bearing Planocerid Flatworm (Platyhelminthes: Acotylea) in the Ryukyu Islands, Japan
Mar. Drugs 2018, 16(1), 37; doi:10.3390/md16010037
Received: 10 December 2017 / Revised: 28 December 2017 / Accepted: 17 January 2018 / Published: 19 January 2018
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Abstract
Polyclad flatworms comprise a highly diverse and cosmopolitan group of marine turbellarians. Although some species of the genera Planocera and Stylochoplana are known to be tetrodotoxin (TTX)-bearing, there are few new reports. In this study, planocerid-like flatworm specimens were found in the sea
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Polyclad flatworms comprise a highly diverse and cosmopolitan group of marine turbellarians. Although some species of the genera Planocera and Stylochoplana are known to be tetrodotoxin (TTX)-bearing, there are few new reports. In this study, planocerid-like flatworm specimens were found in the sea bottom off the waters around the Ryukyu Islands, Japan. The bodies were translucent with brown reticulate mottle, contained two conical tentacles with eye spots clustered at the base, and had a slightly frilled-body margin. Each specimen was subjected to TTX extraction followed by liquid chromatography with tandem mass spectrometry analysis. Mass chromatograms were found to be identical to those of the TTX standards. The TTX amounts in the two flatworm specimens were calculated to be 468 and 3634 μg. Their external morphology was found to be identical to that of Planocera heda. Phylogenetic analysis based on the sequences of the 28S rRNA gene and cytochrome-c oxidase subunit I gene also showed that both specimens clustered with the flatworms of the genus Planocera (Planocera multitentaculata and Planocera reticulata). This fact suggests that there might be other Planocera species that also possess highly concentrated TTX, contributing to the toxification of TTX-bearing organisms, including fish. Full article
(This article belongs to the Special Issue Tetrodotoxin)
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Open AccessArticle Twenty-Nine New Limonoids with Skeletal Diversity from the Mangrove Plant, Xylocarpus moluccensis
Mar. Drugs 2018, 16(1), 38; doi:10.3390/md16010038
Received: 11 December 2017 / Revised: 10 January 2018 / Accepted: 17 January 2018 / Published: 19 January 2018
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Abstract
Twenty-nine new limonoids—named xylomolins A1–A7, B1–B2, C1–C2, D–F, G1–G5, H–I, J1–J2, K1–K2, L1–L2, and M–N,
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Twenty-nine new limonoids—named xylomolins A1–A7, B1–B2, C1–C2, D–F, G1–G5, H–I, J1–J2, K1–K2, L1–L2, and M–N, were isolated from the seeds of the mangrove plant, Xylocarpus moluccensis. Compounds 113 are mexicanolides with one double bond or two conjugated double bonds, while 14 belongs to a small group of mexicanolides with an oxygen bridge between C1 and C8. Compounds 1519 are khayanolides containing a Δ8,14 double bond, whereas 20 and 21 are rare khayanolides containing a Δ14,15 double bond and Δ8,9, Δ14,15 conjugated double bonds, respectively. Compounds 22 and 23 are unusual limonoids possessing a (Z)-bicyclo[5.2.1]dec-3-en-8-one motif, while 24 and 25 are 30-ketophragmalins with Δ8,9, Δ14,15 conjugated double bonds. Compounds 26 and 27 are phragmalin 8,9,30-ortho esters, whereas 28 and 29 are azadirone and andirobin derivatives, respectively. The structures of these compounds, including absolute configurations of 1519, 2123, and 26, were established by HRESIMS, extensive 1D and 2D NMR investigations, and the comparison of experimental electronic circular dichroism (ECD) spectra. The absolute configuration of 1 was unequivocally established by single-crystal X-ray diffraction analysis, obtained with Cu Kα radiation. The diverse cyclization patterns of 129 reveal the strong flexibility of skeletal plasticity in the limonoid biosynthesis of X. moluccensis. Compound 23 exhibited weak antitumor activity against human triple-negative breast MD-MBA-231 cancer cells with an IC50 value of 37.7 μM. Anti-HIV activities of 1, 3, 8, 10, 11, 14, 20, 2325, and 27 were tested in vitro. However, no compounds showed potent inhibitory activity. Full article
(This article belongs to the Special Issue Bioactive Compounds from Mangroves and Their-Associated Microbes)
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Open AccessReview Marine Alkylpurines: A Promising Group of Bioactive Marine Natural Products
Mar. Drugs 2018, 16(1), 6; doi:10.3390/md16010006
Received: 30 November 2017 / Revised: 16 December 2017 / Accepted: 19 December 2017 / Published: 1 January 2018
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Abstract
Marine secondary metabolites with a purine motif in their structure are presented in this review. The alkylpurines are grouped according to the size of the alkyl substituents and their location on the purine ring. Aspects related to the marine source, chemical structure and
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Marine secondary metabolites with a purine motif in their structure are presented in this review. The alkylpurines are grouped according to the size of the alkyl substituents and their location on the purine ring. Aspects related to the marine source, chemical structure and biological properties are considered together with synthetic approaches towards the natural products and bioactive analogues. This review contributes to studies of structure–activity relationships for these metabolites and highlights the potential of the sea as a source of new lead compounds in diverse therapeutic fields. Full article
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Open AccessFeature PaperReview Secondary Metabolites of Mangrove-Associated Strains of Talaromyces
Mar. Drugs 2018, 16(1), 12; doi:10.3390/md16010012
Received: 8 November 2017 / Revised: 24 December 2017 / Accepted: 28 December 2017 / Published: 6 January 2018
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Abstract
Boosted by the general aim of exploiting the biotechnological potential of the microbial component of biodiversity, research on the secondary metabolite production of endophytic fungi has remarkably increased in the past few decades. Novel compounds and bioactivities have resulted from this work, which
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Boosted by the general aim of exploiting the biotechnological potential of the microbial component of biodiversity, research on the secondary metabolite production of endophytic fungi has remarkably increased in the past few decades. Novel compounds and bioactivities have resulted from this work, which has stimulated a more thorough consideration of various natural ecosystems as conducive contexts for the discovery of new drugs. Thriving at the frontier between land and sea, mangrove forests represent one of the most valuable areas in this respect. The present paper offers a review of the research on the characterization and biological activities of secondary metabolites from manglicolous strains of species belonging to the genus Talaromyces. Aspects concerning the opportunity for a more reliable identification of this biological material in the light of recent taxonomic revisions are also discussed. Full article
Open AccessReview Sponges: A Reservoir of Genes Implicated in Human Cancer
Mar. Drugs 2018, 16(1), 20; doi:10.3390/md16010020
Received: 31 October 2017 / Revised: 21 December 2017 / Accepted: 4 January 2018 / Published: 10 January 2018
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Abstract
Recently, it was shown that the majority of genes linked to human diseases, such as cancer genes, evolved in two major evolutionary transitions—the emergence of unicellular organisms and the transition to multicellularity. Therefore, it has been widely accepted that the majority of disease-related
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Recently, it was shown that the majority of genes linked to human diseases, such as cancer genes, evolved in two major evolutionary transitions—the emergence of unicellular organisms and the transition to multicellularity. Therefore, it has been widely accepted that the majority of disease-related genes has already been present in species distantly related to humans. An original way of studying human diseases relies on analyzing genes and proteins that cause a certain disease using model organisms that belong to the evolutionary level at which these genes have emerged. This kind of approach is supported by the simplicity of the genome/proteome, body plan, and physiology of such model organisms. It has been established for quite some time that sponges are an ideal model system for such studies, having a vast variety of genes known to be engaged in sophisticated processes and signalling pathways associated with higher animals. Sponges are considered to be the simplest multicellular animals and have changed little during evolution. Therefore, they provide an insight into the metazoan ancestor genome/proteome features. This review compiles current knowledge of cancer-related genes/proteins in marine sponges. Full article
(This article belongs to the collection Marine Compounds and Cancer) Printed Edition available
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Open AccessReview A Review of the Biological Activities of Microalgal Carotenoids and Their Potential Use in Healthcare and Cosmetic Industries
Mar. Drugs 2018, 16(1), 26; doi:10.3390/md16010026
Received: 17 November 2017 / Revised: 8 January 2018 / Accepted: 8 January 2018 / Published: 12 January 2018
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Abstract
Carotenoids are natural pigments that play pivotal roles in many physiological functions. The characteristics of carotenoids, their effects on health, and the cosmetic benefits of their usage have been under investigation for a long time; however, most reviews on this subject focus on
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Carotenoids are natural pigments that play pivotal roles in many physiological functions. The characteristics of carotenoids, their effects on health, and the cosmetic benefits of their usage have been under investigation for a long time; however, most reviews on this subject focus on carotenoids obtained from several microalgae, vegetables, fruits, and higher plants. Recently, microalgae have received much attention due to their abilities in producing novel bioactive metabolites, including a wide range of different carotenoids that can provide for health and cosmetic benefits. The main objectives of this review are to provide an updated view of recent work on the health and cosmetic benefits associated with carotenoid use, as well as to provide a list of microalgae that produce different types of carotenoids. This review could provide new insights to researchers on the potential role of carotenoids in improving human health. Full article
(This article belongs to the collection Marine Carotenoids)
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Open AccessReview Facial Bone Reconstruction Using both Marine or Non-Marine Bone Substitutes: Evaluation of Current Outcomes in a Systematic Literature Review
Mar. Drugs 2018, 16(1), 27; doi:10.3390/md16010027
Received: 2 November 2017 / Revised: 12 December 2017 / Accepted: 22 December 2017 / Published: 13 January 2018
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Abstract
The aim of the present investigation was to systematically analyse the literature on the facial bone reconstruction defect using marine collagen or not and to evaluate a predictable treatment for their clinical management. The revision has been performed by searched MEDLINE and EMBASE
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The aim of the present investigation was to systematically analyse the literature on the facial bone reconstruction defect using marine collagen or not and to evaluate a predictable treatment for their clinical management. The revision has been performed by searched MEDLINE and EMBASE databases from 2007 to 2017. Clinical trials and animal in vitro studies that had reported the application of bone substitutes or not for bone reconstruction defect and using marine collagen or other bone substitute material were recorded following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The first selection involved 1201 citations. After screening and evaluation of suitability, 39 articles were added at the revision process. Numerous discrepancies among the papers about bone defects morphology, surgical protocols, and selection of biomaterials were found. All selected manuscripts considered the final clinical success after the facial bone reconstruction applying bone substitutes. However, the scientific evidence regarding the vantage of the appliance of a biomaterial versus autologous bone still remains debated. Marine collagen seems to favor the dimensional stability of the graft and it could be an excellent carrier for growth factors. Full article
(This article belongs to the Special Issue Collagen from Marine Biological Source and Medical Applications)
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