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1290 KiB

Open AccessArticle

Effect of Salicornia herbacea on Osteoblastogenesis and Adipogenesis in Vitro

by Fatih Karadeniz, Jung-Ae Kim, Byul-Nim Ahn, Myeong Sook Kwon and Chang-Suk Kong

Mar. Drugs 2014, 12(10), 5132-5147; https://doi.org/10.3390/md12105132 - 10 Oct 2014

Cited by 20 | Viewed by 8044

Abstract

Bone-related complications are among the highest concerning metabolic diseases in the modern world. Bone fragility and susceptibility to fracture increase with age and diseases like osteoporosis. Elevated adipogenesis in bone results in osteoporosis and loss of bone mass when coupled with lack of [...] Read more.

Bone-related complications are among the highest concerning metabolic diseases in the modern world. Bone fragility and susceptibility to fracture increase with age and diseases like osteoporosis. Elevated adipogenesis in bone results in osteoporosis and loss of bone mass when coupled with lack of osteoblastogenesis. In this study the potential effect of Salicornia herbacea extract against osteoporotic conditions was evaluated. Adipogenesis inhibitory effect of S. herbacea has been evidenced by decreased lipid accumulation of differentiating cells and expression levels of crucial adipogenesis markers in 3T3-L1 pre-adipocytes. S. herbacea treatment reduced the lipid accumulation by 25% of the control. In addition, mRNA expression of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α and sterol regulatory element binding protein (SREBP)1c were inhibited by the presence of S. herbacea. Bone formation enhancement effect of S. herbacea was also confirmed in MC3T3-E1 pre-osteoblasts. The presence of S. herbacea significantly elevated the alkaline phosphatase (ALP) activity by 120% at a concentration of 100 μg/mL in differentiating osteoblasts. S. herbacea also significantly increased the expression of osteoblastogenesis indicators, ALP, bone morphogenetic protein (BMP)-2, osteocalcin and collagen type I (collagen-I). In conclusion, S. herbacea possess potential to be utilized as a source of anti-osteoporotic agent that can inhibit adipogenesis while promoting osteoblastogenesis. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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600 KiB

Open AccessArticle

Additional Evidence of the Trypanocidal Action of (−)-Elatol on Amastigote Forms through the Involvement of Reactive Oxygen Species

by Vânia Cristina Desoti, Danielle Lazarin-Bidóia, Daniela Bueno Sudatti, Renato Crespo Pereira, Tania Ueda-Nakamura, Celso Vataru Nakamura and Sueli De Oliveira Silva

Mar. Drugs 2014, 12(9), 4973-4983; https://doi.org/10.3390/md12094973 - 25 Sep 2014

Cited by 9 | Viewed by 5948

Abstract

Chagas’ disease, a vector-transmitted infectious disease, is caused by the protozoa parasite Trypanosoma cruzi. Drugs that are currently available for the treatment of this disease are unsatisfactory, making the search for new chemotherapeutic agents a priority. We recently described the trypanocidal action [...] Read more.

Chagas’ disease, a vector-transmitted infectious disease, is caused by the protozoa parasite Trypanosoma cruzi. Drugs that are currently available for the treatment of this disease are unsatisfactory, making the search for new chemotherapeutic agents a priority. We recently described the trypanocidal action of (−)-elatol, extracted from the macroalga Laurencia dendroidea. However, nothing has been described about the mechanism of action of this compound on amastigotes that are involved in the chronic phase of Chagas’ disease. The goal of the present study was to evaluate the effect of (−)-elatol on the formation of superoxide anions (O₂^•⁻), DNA fragmentation, and autophagy in amastigotes of T. cruzi to elucidate the possible mechanism of the trypanocidal action of (−)-elatol. Treatment of the amastigotes with (−)-elatol increased the formation of O₂^•− at all concentrations of (−)-elatol assayed compared with untreated parasites. Increased fluorescence was observed in parasites treated with (−)-elatol, indicating DNA fragmentation and the formation of autophagic compartments. The results suggest that the trypanocidal action of (−)-elatol might involve the induction of the autophagic and apoptotic death pathways triggered by an imbalance of the parasite’s redox metabolism. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Production of Avaroferrin and Putrebactin by Heterologous Expression of a Deep-Sea Metagenomic DNA

by Masaki J. Fujita and Ryuichi Sakai

Mar. Drugs 2014, 12(9), 4799-4809; https://doi.org/10.3390/md12094799 - 12 Sep 2014

Cited by 18 | Viewed by 7901

Abstract

The siderophore avaroferrin (1), an inhibitor of Vibrio swarming that was recently identified in Shewanella algae B516, was produced by heterologous expression of the biosynthetic gene cluster cloned from a deep-sea sediment metagenomic DNA, together with two analogues, bisucaberin (2 [...] Read more.

The siderophore avaroferrin (1), an inhibitor of Vibrio swarming that was recently identified in Shewanella algae B516, was produced by heterologous expression of the biosynthetic gene cluster cloned from a deep-sea sediment metagenomic DNA, together with two analogues, bisucaberin (2) and putrebactin (3). Avaroferrin (1) is a macrocyclic heterodimer of N-hydroxy-N-succinyl cadaverine (4) and N-hydroxy-N-succinyl-putrescine (5), whereas analogues 2 and 3 are homodimers of 4 and 5, respectively. Heterologous expression of two other related genes from culturable marine bacteria resulted in production of compounds 1–3, but in quite different proportions compared with production through expression of the metagenomic DNA. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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689 KiB

Open AccessArticle

Lipids and Fatty Acids of Nudibranch Mollusks: Potential Sources of Bioactive Compounds

by Natalia V. Zhukova

Mar. Drugs 2014, 12(8), 4578-4592; https://doi.org/10.3390/md12084578 - 19 Aug 2014

Cited by 42 | Viewed by 9750

Abstract

The molecular diversity of chemical compounds found in marine animals offers a good chance for the discovery of novel bioactive compounds of unique structures and diverse biological activities. Nudibranch mollusks, which are not protected by a shell and produce chemicals for various ecological [...] Read more.

The molecular diversity of chemical compounds found in marine animals offers a good chance for the discovery of novel bioactive compounds of unique structures and diverse biological activities. Nudibranch mollusks, which are not protected by a shell and produce chemicals for various ecological uses, including defense against predators, have attracted great interest for their lipid composition. Lipid analysis of eight nudibranch species revealed dominant phospholipids, sterols and monoalkyldiacylglycerols. Among polar lipids, 1-alkenyl-2-acyl glycerophospholipids (plasmalogens) and ceramide-aminoethyl phosphonates were found in the mollusks. The fatty acid compositions of the nudibranchs differed greatly from those of other marine gastropods and exhibited a wide diversity: very long chain fatty acids known as demospongic acids, a series of non-methylene-interrupted fatty acids, including unusual 21:2∆7,13, and an abundance of various odd and branched fatty acids typical of bacteria. Symbiotic bacteria revealed in some species of nudibranchs participate presumably in the production of some compounds serving as a chemical defense for the mollusks. The unique fatty acid composition of the nudibranchs is determined by food supply, inherent biosynthetic activities and intracellular symbiotic microorganisms. The potential of nudibranchs as a source of biologically active lipids and fatty acids is also discussed. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Nocapyrones: α- and γ-Pyrones from a Marine-Derived Nocardiopsis sp.

by Youngju Kim, Hiromu Ogura, Kazuaki Akasaka, Tsutomu Oikawa, Nobuyasu Matsuura, Chiaki Imada, Hisato Yasuda and Yasuhiro Igarashi

Mar. Drugs 2014, 12(7), 4110-4125; https://doi.org/10.3390/md12074110 - 8 Jul 2014

Cited by 45 | Viewed by 7796

Abstract

One new α-pyrone (nocapyrone R (1)), and three known γ-pyrones (nocapyrones B, H and L (2–4)) were isolated from the culture extract of a Nocardiopsis strain collected from marine sediment. Structures of these compounds were determined on [...] Read more.

One new α-pyrone (nocapyrone R (1)), and three known γ-pyrones (nocapyrones B, H and L (2–4)) were isolated from the culture extract of a Nocardiopsis strain collected from marine sediment. Structures of these compounds were determined on the basis of spectroscopic data including NMR and MS. γ-Pyrones 2–4 were found to induce adiponectin production in murine ST-13 preadipocyte cells but the α-pyrone 1 had no activity. The absolute configuration of the anteiso-methyl branching in 4 was determined by HPLC comparison of a degraded product of 4 with standard samples as a 2:3 enantiomeric mixture of (R)- and (S)-isomers. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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774 KiB

Open AccessArticle

Oleosome-Associated Protein of the Oleaginous Diatom Fistulifera solaris Contains an Endoplasmic Reticulum-Targeting Signal Sequence

by Yoshiaki Maeda, Yoshihiko Sunaga, Tomoko Yoshino and Tsuyoshi Tanaka

Mar. Drugs 2014, 12(7), 3892-3903; https://doi.org/10.3390/md12073892 - 30 Jun 2014

Cited by 22 | Viewed by 7735

Abstract

Microalgae tend to accumulate lipids as an energy storage material in the specific organelle, oleosomes. Current studies have demonstrated that lipids derived from microalgal oleosomes are a promising source of biofuels, while the oleosome formation mechanism has not been fully elucidated. Oleosome-associated proteins [...] Read more.

Microalgae tend to accumulate lipids as an energy storage material in the specific organelle, oleosomes. Current studies have demonstrated that lipids derived from microalgal oleosomes are a promising source of biofuels, while the oleosome formation mechanism has not been fully elucidated. Oleosome-associated proteins have been identified from several microalgae to elucidate the fundamental mechanisms of oleosome formation, although understanding their functions is still in infancy. Recently, we discovered a diatom-oleosome-associated-protein 1 (DOAP1) from the oleaginous diatom, Fistulifera solaris JPCC DA0580. The DOAP1 sequence implied that this protein might be transported into the endoplasmic reticulum (ER) due to the signal sequence. To ensure this, we fused the signal sequence to green fluorescence protein. The fusion protein distributed around the chloroplast as like a meshwork membrane structure, indicating the ER localization. This result suggests that DOAP1 could firstly localize at the ER, then move to the oleosomes. This study also demonstrated that the DOAP1 signal sequence allowed recombinant proteins to be specifically expressed in the ER of the oleaginous diatom. It would be a useful technique for engineering the lipid synthesis pathways existing in the ER, and finally controlling the biofuel quality. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Pigment Cell Differentiation in Sea Urchin Blastula-Derived Primary Cell Cultures

by Natalya V. Ageenko, Konstantin V. Kiselev, Pavel S. Dmitrenok and Nelly A. Odintsova

Mar. Drugs 2014, 12(7), 3874-3891; https://doi.org/10.3390/md12073874 - 27 Jun 2014

Cited by 20 | Viewed by 7873

Abstract

The quinone pigments of sea urchins, specifically echinochrome and spinochromes, are known for their effective antioxidant, antibacterial, antifungal, and antitumor activities. We developed in vitro technology for inducing pigment differentiation in cell culture. The intensification of the pigment differentiation was accompanied by a [...] Read more.

The quinone pigments of sea urchins, specifically echinochrome and spinochromes, are known for their effective antioxidant, antibacterial, antifungal, and antitumor activities. We developed in vitro technology for inducing pigment differentiation in cell culture. The intensification of the pigment differentiation was accompanied by a simultaneous decrease in cell proliferation. The number of pigment cells was two-fold higher in the cells cultivated in the coelomic fluids of injured sea urchins than in those intact. The possible roles of the specific components of the coelomic fluids in the pigment differentiation process and the quantitative measurement of the production of naphthoquinone pigments during cultivation were examined by MALDI and electrospray ionization mass spectrometry. Echinochrome A and spinochrome E were produced by the cultivated cells of the sand dollar Scaphechinus mirabilis in all tested media, while only spinochromes were found in the cultivated cells of another sea urchin, Strongylocentrotus intermedius. The expression of genes associated with the induction of pigment differentiation was increased in cells cultivated in the presence of shikimic acid, a precursor of naphthoquinone pigments. Our results should contribute to the development of new techniques in marine biotechnology, including the generation of cell cultures producing complex bioactive compounds with therapeutic potential. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Type II Collagen and Gelatin from Silvertip Shark (Carcharhinus albimarginatus) Cartilage: Isolation, Purification, Physicochemical and Antioxidant Properties

by Elango Jeevithan, Bin Bao, Yongshi Bu, Yu Zhou, Qingbo Zhao and Wenhui Wu

Mar. Drugs 2014, 12(7), 3852-3873; https://doi.org/10.3390/md12073852 - 27 Jun 2014

Cited by 115 | Viewed by 13445

Abstract

Type II acid soluble collagen (CIIA), pepsin soluble collagen (CIIP) and type II gelatin (GII) were isolated from silvertip shark (Carcharhinus albimarginatus) cartilage and examined for their physicochemical and antioxidant properties. GII had a higher hydroxyproline content (173 mg/g) than the [...] Read more.

Type II acid soluble collagen (CIIA), pepsin soluble collagen (CIIP) and type II gelatin (GII) were isolated from silvertip shark (Carcharhinus albimarginatus) cartilage and examined for their physicochemical and antioxidant properties. GII had a higher hydroxyproline content (173 mg/g) than the collagens and cartilage. CIIA, CIIP and GII were composed of two identical α₁ and β chains and were characterized as type II. Amino acid analysis of CIIA, CIIP and GII indicated imino acid contents of 150, 156 and 153 amino acid residues per 1000 residues, respectively. Differing Fourier transform infrared (FTIR) spectra of CIIA, CIIP and GII were observed, which suggested that the isolation process affected the secondary structure and molecular order of collagen, particularly the triple-helical structure. The denaturation temperature of GII (32.5 °C) was higher than that of CIIA and CIIP. The antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl radicals and the reducing power of CIIP was greater than that of CIIA and GII. SEM microstructure of the collagens depicted a porous, fibrillary and multi-layered structure. Accordingly, the physicochemical and antioxidant properties of type II collagens (CIIA, CIIP) and GII isolated from shark cartilage were found to be suitable for biomedical applications. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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513 KiB

Open AccessArticle

Bis(2,3-dibromo-4,5-dihydroxybenzyl) Ether, a Marine Algae Derived Bromophenol, Inhibits the Growth of Botrytis cinerea and Interacts with DNA Molecules

by Ming Liu, Genzhu Wang, Lin Xiao, Xuanli Xu, Xiaohui Liu, Pingxiang Xu and Xiukun Lin

Mar. Drugs 2014, 12(7), 3838-3851; https://doi.org/10.3390/md12073838 - 27 Jun 2014

Cited by 44 | Viewed by 7542

Abstract

Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) is a bromophenol isolated from marine algae. Previous reports have shown that BDDE possesses cytotoxic and antibacterial activity. In the present study, we demonstrate that BDDE displays broad-spectrum antifungal activities, especially on Botrytis cinerea. BDDE inhibits the growth of [...] Read more.

Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) is a bromophenol isolated from marine algae. Previous reports have shown that BDDE possesses cytotoxic and antibacterial activity. In the present study, we demonstrate that BDDE displays broad-spectrum antifungal activities, especially on Botrytis cinerea. BDDE inhibits the growth of B. cinerea cultured on a solid medium of potato dextrose agar (PDA) as well as on the potato dextrose broth (PDB) medium. Moreover, BDDE decreases the incidence of fruit decay and severity of strawberries infected with B. cinerea. Further studies have revealed that BDDE decreases the germination rate and inhibits the mycelial growth of B. cinerea. The inhibition mechanisms are related to the disruption of the cell membrane integrity in B. cinerea spores and newly formed germ tubes. This study also suggests that BDDE possibly interacts with DNA via intercalation and minor groove binding. The studies provide evidence that BDDE has potential application in the control of gray mold after fruit harvest and the compound could serve as a candidate or lead template for rational drug design and for the development of antifungal agents. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Analysis of the Biomass Composition of the Demosponge Amphimedon queenslandica on Heron Island Reef, Australia

by Jabin R. Watson, Timothy C. R. Brennan, Bernard M. Degnan, Sandie M. Degnan and Jens O. Krömer

Mar. Drugs 2014, 12(6), 3733-3753; https://doi.org/10.3390/md12063733 - 23 Jun 2014

Cited by 5 | Viewed by 6239

Abstract

Marine sponges are a potential source of important pharmaceutical drugs, the commercialisation of which is restricted by the difficulties of obtaining a sufficient and regular supply of biomass. One way to optimize commercial cell lines for production is the in-depth characterization and target [...] Read more.

Marine sponges are a potential source of important pharmaceutical drugs, the commercialisation of which is restricted by the difficulties of obtaining a sufficient and regular supply of biomass. One way to optimize commercial cell lines for production is the in-depth characterization and target identification through genome scale metabolic modeling and flux analysis. By applying these tools to a sponge, we hope to gain insights into how biomass is formed. We chose Amphimedon queenslandica as it has an assembled and annotated genome, a prerequisite for genome scale modeling. The first stepping stone on the way to metabolic flux analysis in a sponge holobiont, is the characterization of its biomass composition. In this study we quantified the macromolecular composition and investigated the variation between and within sponges of a single population. We found lipids and protein to be the most abundant macromolecules, while carbohydrates were the most variable. We also analysed the composition and abundance of the fatty acids and amino acids, the important building blocks required to synthesise the abundant macromolecule types, lipids, and protein. These data complement the extensive genomic information available for A. queenslandica and lay the basis for genome scale modelling and flux analysis. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Chromomycins A₂ and A₃ from Marine Actinomycetes with TRAIL Resistance-Overcoming and Wnt Signal Inhibitory Activities

by Kazufumi Toume, Kentaro Tsukahara, Hanako Ito, Midori A. Arai and Masami Ishibashi

Mar. Drugs 2014, 12(6), 3466-3476; https://doi.org/10.3390/md12063466 - 5 Jun 2014

Cited by 24 | Viewed by 6922

Abstract

A biological screening study of an actinomycetes strain assembly was conducted using a cell-based cytotoxicity assay. The CKK1019 strain was isolated from a sea sand sample. Cytotoxicity-guided fractionation of the CKK1019 strain culture broth, which exhibited cytotoxicity, led to the isolation of chromomycins [...] Read more.

A biological screening study of an actinomycetes strain assembly was conducted using a cell-based cytotoxicity assay. The CKK1019 strain was isolated from a sea sand sample. Cytotoxicity-guided fractionation of the CKK1019 strain culture broth, which exhibited cytotoxicity, led to the isolation of chromomycins A₂ (1) and A₃ (2). 1 and 2 showed potent cytotoxicity against the human gastric adenocarcinoma (AGS) cell line (IC₅₀ 1; 1.7 and 2; 22.1 nM), as well as strong inhibitory effects against TCF/β-catenin transcription (IC₅₀ 1; 1.8 and 2; 15.9 nM). 2 showed the ability to overcome tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance. To the best of our knowledge, the effects of chromomycins A₂ (1) and A₃ (2) on TRAIL resistance-overcoming activity, and on the Wnt signaling pathway, have not been reported previously. Thus, 1 and 2 warrant potential drug lead studies in relation to TRAIL-resistant and Wnt signal-related diseases and offer potentially useful chemical probes for investigating TRAIL resistance and the Wnt signaling pathway. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Characterization of a Novel Conus bandanus Conopeptide Belonging to the M-Superfamily Containing Bromotryptophan

by Bao Nguyen, Jean-Pierre Le Caer, Gilles Mourier, Robert Thai, Hung Lamthanh, Denis Servent, Evelyne Benoit and Jordi Molgó

Mar. Drugs 2014, 12(6), 3449-3465; https://doi.org/10.3390/md12063449 - 5 Jun 2014

Cited by 12 | Viewed by 7210

Abstract

A novel conotoxin (conopeptide) was biochemically characterized from the crude venom of the molluscivorous marine snail, Conus bandanus (Hwass in Bruguière, 1792), collected in the south-central coast of Vietnam. The peptide was identified by screening bromotryptophan from chromatographic fractions of the crude venom. [...] Read more.

A novel conotoxin (conopeptide) was biochemically characterized from the crude venom of the molluscivorous marine snail, Conus bandanus (Hwass in Bruguière, 1792), collected in the south-central coast of Vietnam. The peptide was identified by screening bromotryptophan from chromatographic fractions of the crude venom. Tandem mass spectrometry techniques were used to detect and localize different post-translational modifications (PTMs) present in the BnIIID conopeptide. The sequence was confirmed by Edman’s degradation and mass spectrometry revealing that the purified BnIIID conopeptide had 15 amino acid residues, with six cysteines at positions 1, 2, 7, 11, 13, and 14, and three PTMs: bromotryptophan, γ-carboxy glutamate, and amidated aspartic acid, at positions “4”, “5”, and “15”, respectively. The BnIIID peptide was synthesized for comparison with the native peptide. Homology comparison with conopeptides having the III-cysteine framework (–CCx₁x₂x₃x₄Cx₁x₂x₃Cx₁CC–) revealed that BnIIID belongs to the M-1 family of conotoxins. This is the first report of a member of the M-superfamily containing bromotryptophan as PTM. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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1485 KiB

Open AccessArticle

Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish

by Si-Mei Long, Feng-Yin Liang, Qi Wu, Xi-Lin Lu, Xiao-Li Yao, Shi-Chang Li, Jing Li, Huanxing Su, Ji-Yan Pang and Zhong Pei

Mar. Drugs 2014, 12(6), 3307-3322; https://doi.org/10.3390/md12063307 - 30 May 2014

Cited by 18 | Viewed by 9481

Abstract

High-throughput behavior-based screen in zebrafish is a powerful approach for the discovery of novel neuroactive small molecules for treatment of nervous system diseases such as epilepsy. To identify neuroactive small molecules, we first screened 36 compounds (1–36) derived from [...] Read more.

High-throughput behavior-based screen in zebrafish is a powerful approach for the discovery of novel neuroactive small molecules for treatment of nervous system diseases such as epilepsy. To identify neuroactive small molecules, we first screened 36 compounds (1–36) derived from marine natural products xyloketals and marine isoprenyl phenyl ether obtained from the mangrove fungus. Compound 1 demonstrated the most potent inhibition on the locomotor activity in larval zebrafish. Compounds 37–42 were further synthesized and their potential anti-epilepsy action was then examined in a PTZ-induced epilepsy model in zebrafish. Compound 1 and compounds 39, 40 and 41 could significantly attenuate PTZ-induced locomotor hyperactivity and elevation of c-fos mRNA in larval zebrafish. Compound 40 showed the most potent inhibitory action against PTZ-induced hyperactivity. The structure-activity analysis showed that the OH group at 12-position played a critical role and the substituents at the 13-position were well tolerated in the inhibitory activity of xyloketal derivatives. Thus, these derivatives may provide some novel drug candidates for the treatment of epilepsy. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

The Protective Effect of Fucoidan in Rats with Streptozotocin-Induced Diabetic Nephropathy

by Jing Wang, Huaide Liu, Ning Li, Quanbin Zhang and Hong Zhang

Mar. Drugs 2014, 12(6), 3292-3306; https://doi.org/10.3390/md12063292 - 30 May 2014

Cited by 74 | Viewed by 8860

Abstract

Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) [...] Read more.

Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the β2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Profiling of Polar Lipids in Marine Oleaginous Diatom Fistulifera solaris JPCC DA0580: Prediction of the Potential Mechanism for Eicosapentaenoic Acid-Incorporation into Triacylglycerol

by Yue Liang, Yoshiaki Maeda, Tomoko Yoshino, Mitsufumi Matsumoto and Tsuyoshi Tanaka

Mar. Drugs 2014, 12(6), 3218-3230; https://doi.org/10.3390/md12063218 - 28 May 2014

Cited by 27 | Viewed by 8645

Abstract

The marine oleaginous diatom Fistulifera solaris JPCC DA0580 is a candidate for biodiesel production because of its high lipid productivity. However, the substantial eicosapentaenoic acid (EPA) content in this strain would affect the biodiesel quality. On the other hand, EPA is also known [...] Read more.

The marine oleaginous diatom Fistulifera solaris JPCC DA0580 is a candidate for biodiesel production because of its high lipid productivity. However, the substantial eicosapentaenoic acid (EPA) content in this strain would affect the biodiesel quality. On the other hand, EPA is also known as the essential health supplement for humans. EPAs are mainly incorporated into glycerolipids in the microalgal cell instead of the presence as free fatty acids. Therefore, the understanding of the EPA biosynthesis including the incorporation of the EPA into glycerolipids especially triacylglycerol (TAG) is fundamental for regulating EPA content for different purposes. In this study, in order to identify the biosynthesis pathway for the EPA-containing TAG species, a lipidomic characterization of the EPA-enriched polar lipids was performed by using direct infusion electrospray ionization (ESI)-Q-TRAP-MS and MS/MS analyses. The determination of the fatty acid positional distribution showed that the sn-2 position of all the chloroplast lipids and part of phosphatidylcholine (PC) species was occupied by C16 fatty acids. This result suggested the critical role of the chloroplast on the lipid synthesis in F. solaris. Furthermore, the exclusive presence of C18 fatty acids in PC highly indicated the biosynthesis of EPA on PC. Finally, the PC-based acyl-editing and head group exchange processes were proposed to be essential for the incorporation of EPA into TAG and chloroplast lipids. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B

by Panpan Ye, Ling Shen, Wei Jiang, Ying Ye, Chen-Tung Arthur Chen, Xiaodan Wu, Kuiwu Wang and Bin Wu

Mar. Drugs 2014, 12(6), 3203-3217; https://doi.org/10.3390/md12063203 - 28 May 2014

Cited by 32 | Viewed by 7443

Abstract

A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were isolated from Xenograpsus testudinatus. X. [...] Read more.

A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were isolated from Xenograpsus testudinatus. X. testudinatus lives at extreme, toxic habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. The known compound clavatustide B was also isolated and purified. This is the first example of a new hydrothermal vent microbial secondary metabolite produced in response to abiotic Zn treatment. The structures were established by spectroscopic means. The regulation of G1-S transition in hepatocellular carcinoma cell lines by clavatustide B was observed in our previous study. The purpose of the present study was to verify these results in other types of cancer cell lines and elucidate the possible molecular mechanism for the anti-cancer activities of clavatustide B. In different human cancer cell lines, including pancreatic cancer (Panc-1), gastric cancer (MGC-803), colorectal cancer (SW-480), retinoblastoma (WERI-Rb-1) and prostate cancer (PC3), clavatustide B efficiently suppressed cell proliferations in a dose-dependent manner. Although different cancer cell lines presented variety in Max effect dose and IC₅₀ dose, all cancer cell lines showed a lower Max effect dose and IC₅₀ dose compared with human fibroblasts (hFB) (p < 0.05). Moreover, significant accumulations in G1 phases and a reduction in S phases (p < 0.05) were observed under clavatustide B treatment. The expression levels of 2622 genes including 39 cell cycle-associated genes in HepG2 cells were significantly altered by the treatment with 15 μg/mL clavatustide B after 48 h. CCNE2 (cyclin E2) was proved to be the key regulator of clavatustide B-induced G1-S transition blocking in several cancer cell lines by using real-time PCR. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Cracking the Cytotoxicity Code: Apoptotic Induction of 10-Acetylirciformonin B is Mediated through ROS Generation and Mitochondrial Dysfunction

by Huei-Chuan Shih, Mohamed El-Shazly, Yung-Shun Juan, Chao-Yuan Chang, Jui-Hsin Su, Yu-Cheng Chen, Shou-Ping Shih, Huei-Mei Chen, Yang-Chang Wu and Mei-Chin Lu

Mar. Drugs 2014, 12(5), 3072-3090; https://doi.org/10.3390/md12053072 - 22 May 2014

Cited by 34 | Viewed by 7768

Abstract

A marine furanoterpenoid derivative, 10-acetylirciformonin B (10AB), was found to inhibit the proliferation of leukemia, hepatoma, and colon cancer cell lines, with selective and significant potency against leukemia cells. It induced DNA damage and apoptosis in leukemia HL 60 cells. To fully understand [...] Read more.

A marine furanoterpenoid derivative, 10-acetylirciformonin B (10AB), was found to inhibit the proliferation of leukemia, hepatoma, and colon cancer cell lines, with selective and significant potency against leukemia cells. It induced DNA damage and apoptosis in leukemia HL 60 cells. To fully understand the mechanism behind the 10AB apoptotic induction against HL 60 cells, we extended our previous findings and further explored the precise molecular targets of 10AB. We found that the use of 10AB increased apoptosis by 8.9%–87.6% and caused disruption of mitochondrial membrane potential (MMP) by 15.2%–95.2% in a dose-dependent manner, as demonstrated by annexin-V/PI and JC-1 staining assays, respectively. Moreover, our findings indicated that the pretreatment of HL 60 cells with N-acetyl-l-cysteine (NAC), a reactive oxygen species (ROS) scavenger, diminished MMP disruption and apoptosis induced by 10AB, suggesting that ROS overproduction plays a crucial rule in the cytotoxic activity of 10AB. The results of a cell-free system assay indicated that 10AB could act as a topoisomerase catalytic inhibitor through the inhibition of topoisomerase IIα. On the protein level, the expression of the anti-apoptotic proteins Bcl-xL and Bcl-2, caspase inhibitors XIAP and survivin, as well as hexokinase II were inhibited by the use of 10AB. On the other hand, the expression of the pro-apoptotic protein Bax was increased after 10AB treatment. Taken together, our results suggest that 10AB-induced apoptosis is mediated through the overproduction of ROS and the disruption of mitochondrial metabolism. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

In Situ Detection of Antibiotic Amphotericin B Produced in Streptomyces nodosus Using Raman Microspectroscopy

by Rimi Miyaoka, Masahito Hosokawa, Masahiro Ando, Tetsushi Mori, Hiro-o Hamaguchi and Haruko Takeyama

Mar. Drugs 2014, 12(5), 2827-2839; https://doi.org/10.3390/md12052827 - 13 May 2014

Cited by 30 | Viewed by 9857

Abstract

The study of spatial distribution of secondary metabolites within microbial cells facilitates the screening of candidate strains from marine environments for functional metabolites and allows for the subsequent assessment of the production of metabolites, such as antibiotics. This paper demonstrates the first application [...] Read more.

The study of spatial distribution of secondary metabolites within microbial cells facilitates the screening of candidate strains from marine environments for functional metabolites and allows for the subsequent assessment of the production of metabolites, such as antibiotics. This paper demonstrates the first application of Raman microspectroscopy for in situ detection of the antifungal antibiotic amphotericin B (AmB) produced by actinomycetes—Streptomyces nodosus. Raman spectra measured from hyphae of S. nodosus show the specific Raman bands, caused by resonance enhancement, corresponding to the polyene chain of AmB. In addition, Raman microspectroscopy enabled us to monitor the time-dependent change of AmB production corresponding to the growth of mycelia. The Raman images of S. nodosus reveal the heterogeneous distribution of AmB within the mycelia and individual hyphae. Moreover, the molecular association state of AmB in the mycelia was directly identified by observed Raman spectral shifts. These findings suggest that Raman microspectroscopy could be used for in situ monitoring of antibiotic production directly in marine microorganisms with a method that is non-destructive and does not require labeling. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Marine Compound Catunaregin Inhibits Angiogenesis through the Modulation of Phosphorylation of Akt and eNOS in vivo and in vitro

by Jun-Xiu Liu, Min-Qi Luo, Meng Xia, Qi Wu, Si-Mei Long, Yaohua Hu, Guang-Chun Gao, Xiao-Li Yao, Mian He, Huanxing Su, Xiong-Ming Luo and Shu-Zhong Yao

Mar. Drugs 2014, 12(5), 2790-2801; https://doi.org/10.3390/md12052790 - 12 May 2014

Cited by 23 | Viewed by 8987

Abstract

Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated [...] Read more.

Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Actinomycetes from Red Sea Sponges: Sources for Chemical and Phylogenetic Diversity

by Usama Ramadan Abdelmohsen, Chen Yang, Hannes Horn, Dina Hajjar, Timothy Ravasi and Ute Hentschel

Mar. Drugs 2014, 12(5), 2771-2789; https://doi.org/10.3390/md12052771 - 12 May 2014

Cited by 66 | Viewed by 15072

Abstract

The diversity of actinomycetes associated with marine sponges collected off Fsar Reef (Saudi Arabia) was investigated in the present study. Forty-seven actinomycetes were cultivated and phylogenetically identified based on 16S rRNA gene sequencing and were assigned to 10 different actinomycete genera. Eight putatively [...] Read more.

The diversity of actinomycetes associated with marine sponges collected off Fsar Reef (Saudi Arabia) was investigated in the present study. Forty-seven actinomycetes were cultivated and phylogenetically identified based on 16S rRNA gene sequencing and were assigned to 10 different actinomycete genera. Eight putatively novel species belonging to genera Kocuria, Mycobacterium, Nocardia, and Rhodococcus were identified based on sequence similarity values below 98.2% to other 16S rRNA gene sequences available in the NCBI database. PCR-based screening for biosynthetic genes including type I and type II polyketide synthases (PKS-I, PKS-II) as well as nonribosomal peptide synthetases (NRPS) showed that 20 actinomycete isolates encoded each at least one type of biosynthetic gene. The organic extracts of nine isolates displayed bioactivity against at least one of the test pathogens, which were Gram-positive and Gram-negative bacteria, fungi, human parasites, as well as in a West Nile Virus protease enzymatic assay. These results emphasize that marine sponges are a prolific resource for novel bioactive actinomycetes with potential for drug discovery. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Discovery of Novel Saponins from the Viscera of the Sea Cucumber Holothuria lessoni

by Yadollah Bahrami, Wei Zhang and Chris Franco

Mar. Drugs 2014, 12(5), 2633-2667; https://doi.org/10.3390/md12052633 - 9 May 2014

Cited by 61 | Viewed by 11987

Abstract

Sea cucumbers, sometimes referred to as marine ginseng, produce numerous compounds with diverse functions and are potential sources of active ingredients for agricultural, nutraceutical, pharmaceutical and cosmeceutical products. We examined the viscera of an Australian sea cucumber Holothuria lessoni Massin et al. 2009, [...] Read more.

Sea cucumbers, sometimes referred to as marine ginseng, produce numerous compounds with diverse functions and are potential sources of active ingredients for agricultural, nutraceutical, pharmaceutical and cosmeceutical products. We examined the viscera of an Australian sea cucumber Holothuria lessoni Massin et al. 2009, for novel bioactive compounds, with an emphasis on the triterpene glycosides, saponins. The viscera were extracted with 70% ethanol, and this extract was purified by a liquid-liquid partition process and column chromatography, followed by isobutanol extraction. The isobutanol saponin-enriched mixture was further purified by high performance centrifugal partition chromatography (HPCPC) with high purity and recovery. The resultant purified polar samples were analyzed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)/MS and electrospray ionization mass spectrometry (ESI-MS)/MS to identify saponins and characterize their molecular structures. As a result, at least 39 new saponins were identified in the viscera of H. lessoni with a high structural diversity, and another 36 reported triterpene glycosides, containing different aglycones and sugar moieties. Viscera samples have provided a higher diversity and yield of compounds than observed from the body wall. The high structural diversity and novelty of saponins from H. lessoni with potential functional activities presents a great opportunity to exploit their applications for industrial, agricultural and pharmaceutical use. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessCommunication

Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation

by Swarna Oli, Usama Ramadan Abdelmohsen, Ute Hentschel and Tanja Schirmeister

Mar. Drugs 2014, 12(5), 2614-2622; https://doi.org/10.3390/md12052614 - 2 May 2014

Cited by 16 | Viewed by 7061

Abstract

In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC₅₀ value of 5 μM and without cytotoxic effects against J774.1 macrophages [...] Read more.

In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC₅₀ value of 5 μM and without cytotoxic effects against J774.1 macrophages at 100 μM concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Antiplatelet and Anticoagulant Effects of Diterpenes Isolated from the Marine Alga, Dictyota menstrualis

by Laura De Andrade Moura, Ana Carolina Marqui de Almeida, Thaisa Francielle Souza Domingos, Fredy Ortiz-Ramirez, Diana Negrão Cavalcanti, Valéria Laneuville Teixeira and André Lopes Fuly

Mar. Drugs 2014, 12(5), 2471-2484; https://doi.org/10.3390/md12052471 - 30 Apr 2014

Cited by 36 | Viewed by 7386

Abstract

Cardiovascular diseases represent a major cause of disability and death worldwide. Therapeutics are available, but they often have unsatisfactory results and may produce side effects. Alternative treatments based on the use of natural products have been extensively investigated, because of their low toxicity [...] Read more.

Cardiovascular diseases represent a major cause of disability and death worldwide. Therapeutics are available, but they often have unsatisfactory results and may produce side effects. Alternative treatments based on the use of natural products have been extensively investigated, because of their low toxicity and side effects. Marine organisms are prime candidates for such products, as they are sources of numerous and complex substances with ecological and pharmacological effects. In this work, we investigated, through in vitro experiments, the effects of three diterpenes (pachydictyol A, isopachydictyol A and dichotomanol) from the Brazilian marine alga, Dictyota menstrualis, on platelet aggregation and plasma coagulation. Results showed that dichotomanol inhibited ADP- or collagen-induced aggregation of platelet-rich plasma (PRP), but failed to inhibit washed platelets (WP). In contrast, pachydictyol A and isopachydictyol A failed to inhibit the aggregation of PRP, but inhibited WP aggregation induced by collagen or thrombin. These diterpenes also inhibited coagulation analyzed by the prothrombin time and activated partial thromboplastin time and on commercial fibrinogen. Moreover, diterpenes inhibited the catalytic activity of thrombin. Theoretical studies using the Osiris Property Explorer software showed that diterpenes have low theoretical toxicity profiles and a drug-score similar to commercial anticoagulant drugs. In conclusion, these diterpenes are promising candidates for use in anticoagulant therapy, and this study also highlights the biotechnological potential of oceans and the importance of bioprospecting to develop medicines. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Development of Pedigree Classification Using Microsatellite and Mitochondrial Markers for Giant Grouper Broodstock (Epinephelus lanceolatus) Management in Taiwan

by Hsiao-Che Kuo, Hao-Hsuan Hsu, Chee Shin Chua, Ting-Yu Wang, Young-Mao Chen and Tzong-Yueh Chen

Mar. Drugs 2014, 12(5), 2397-2407; https://doi.org/10.3390/md12052397 - 30 Apr 2014

Cited by 8 | Viewed by 6510

Abstract

Most giant groupers in the market are derived from inbred stock. Inbreeding can cause trait depression, compromising the animals’ fitness and disease resistance, obligating farmers to apply increased amounts of drugs. In order to solve this problem, a pedigree classification method is needed. [...] Read more.

Most giant groupers in the market are derived from inbred stock. Inbreeding can cause trait depression, compromising the animals’ fitness and disease resistance, obligating farmers to apply increased amounts of drugs. In order to solve this problem, a pedigree classification method is needed. Here, microsatellite and mitochondrial DNA were used as genetic markers to analyze the genetic relationships among giant grouper broodstocks. The 776-bp fragment of high polymorphic mitochondrial D-loop sequence was selected for measuring sibling relatedness. In a sample of 118 giant groupers, 42 haplotypes were categorized, with nucleotide diversity (π) of 0.00773 and haplotype diversity (HD) of 0.983. Furthermore, microsatellites were used for investigation of parentage. Six out of 33 microsatellite loci were selected as markers based on having a high number of alleles and compliance with Hardy-Weinberg equilibrium. Microsatellite profiles based on these loci provide high variability with low combined non-exclusion probability, permitting practical use in aquaculture. The method described here could be used to improve grouper broodstock management and lower the chances of inbreeding. This approach is expected to lead to production of higher quality groupers with higher disease resistance, thereby reducing the need for drug application. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Extraction of Fucoxanthin from Raw Macroalgae excluding Drying and Cell Wall Disruption by Liquefied Dimethyl Ether

by Hideki Kanda, Yuichi Kamo, Siti Machmudah, Wahyudiono and Motonobu Goto

Mar. Drugs 2014, 12(5), 2383-2396; https://doi.org/10.3390/md12052383 - 30 Apr 2014

Cited by 90 | Viewed by 10790

Abstract

Macroalgae are one of potential sources for carotenoids, such as fucoxanthin, which are consumed by humans and animals. This carotenoid has been applied in both the pharmaceutical and food industries. In this study, extraction of fucoxanthin from wet brown seaweed Undaria pinnatifida (water [...] Read more.

Macroalgae are one of potential sources for carotenoids, such as fucoxanthin, which are consumed by humans and animals. This carotenoid has been applied in both the pharmaceutical and food industries. In this study, extraction of fucoxanthin from wet brown seaweed Undaria pinnatifida (water content was 93.2%) was carried out with a simple method using liquefied dimethyl ether (DME) as an extractant in semi-continuous flow-type system. The extraction temperature and absolute pressure were 25 °C and 0.59 MPa, respectively. The liquefied DME was passed through the extractor that filled by U. pinnatifida at different time intervals. The time of experiment was only 43 min. The amount of fucoxanthin could approach to 390 μg/g dry of wet U. pinnatifida when the amount of DME used was 286 g. Compared with ethanol Soxhlet and supercritical CO₂ extraction, which includes drying and cell disruption, the result was quite high. Thus, DME extraction process appears to be a good method for fucoxanthin recovery from U. pinnatifida with improved yields. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Omega-3 Polyunsaturated Fatty Acids Protect Neural Progenitor Cells against Oxidative Injury

by Qiang Liu, Di Wu, Na Ni, Huixia Ren, Chuanming Luo, Chengwei He, Jing-Xuan Kang, Jian-Bo Wan and Huanxing Su

Mar. Drugs 2014, 12(5), 2341-2356; https://doi.org/10.3390/md12052341 - 29 Apr 2014

Cited by 47 | Viewed by 8247

Abstract

The omega-3 polyunsaturated fatty acids (ω-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), derived mainly from fish oil, play important roles in brain development and neuroplasticity. Here, we reported that application of ω-3 PUFAs significantly protected mouse neural progenitor cells (NPCs) against [...] Read more.

The omega-3 polyunsaturated fatty acids (ω-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), derived mainly from fish oil, play important roles in brain development and neuroplasticity. Here, we reported that application of ω-3 PUFAs significantly protected mouse neural progenitor cells (NPCs) against H₂O₂-induced oxidative injury. We also isolated NPCs from transgenic mice expressing the Caenorhabditis elegans fat-1 gene. The fat-1 gene, which is absent in mammals, can add a double bond into an unsaturated fatty acid hydrocarbon chain and convert ω-6 to ω-3 fatty acids. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that a marked decrease in apoptotic cells was found in fat-1 NPCs after oxidative injury with H₂O₂ as compared with wild-type NPCs. Quantitative RT-PCR and Western blot analysis demonstrated a much higher expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcriptional factor for antioxidant genes, in fat-1 NPCs. The results of the study provide evidence that ω-3 PUFAs resist oxidative injury to NPCs. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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A New Benzofuran Glycoside and Indole Alkaloids from a Sponge-Associated Rare Actinomycete, Amycolatopsis sp.

by Yun Kwon, Seong-Hwan Kim, Yoonho Shin, Munhyung Bae, Byung-Yong Kim, Sang Kook Lee, Ki-Bong Oh, Jongheon Shin and Dong-Chan Oh

Mar. Drugs 2014, 12(4), 2326-2340; https://doi.org/10.3390/md12042326 - 22 Apr 2014

Cited by 37 | Viewed by 8414

Abstract

Three new secondary metabolites, amycofuran (1), amycocyclopiazonic acid (2), and amycolactam (3), were isolated from the sponge-associated rare actinomycete Amycolatopsis sp. Based on combined spectroscopic analyses, the structures of 1–3 were determined to be a [...] Read more.

Three new secondary metabolites, amycofuran (1), amycocyclopiazonic acid (2), and amycolactam (3), were isolated from the sponge-associated rare actinomycete Amycolatopsis sp. Based on combined spectroscopic analyses, the structures of 1–3 were determined to be a new benzofuran glycoside and new indole alkaloids related to cyclopiazonic acids, a class that has previously only been reported in fungi. The absolute configurations of 1 and 3 were deduced by ECD calculations, whereas that of 2 was determined using the modified Mosher method. Amycolactam (3) displayed significant cytotoxicity against the gastric cancer cell line SNU638 and the colon cancer cell line HCT116. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Two New Cytotoxic Indole Alkaloids from a Deep-Sea Sediment Derived Metagenomic Clone

by Xia Yan, Xi-Xiang Tang, Lin Chen, Zhi-Wei Yi, Mei-Juan Fang, Zhen Wu and Ying-Kun Qiu

Mar. Drugs 2014, 12(4), 2156-2163; https://doi.org/10.3390/md12042156 - 8 Apr 2014

Cited by 15 | Viewed by 6219

Abstract

Two new indole alkaloids, metagenetriindole A (1) and metagenebiindole A (2), were identified from deep-sea sediment metagenomic clone derived Escherichia coli fermentation broth. The structures of new compounds were elucidated by spectroscopic methods. The two new indole alkaloids demonstrated moderately cytotoxic activity against [...] Read more.

Two new indole alkaloids, metagenetriindole A (1) and metagenebiindole A (2), were identified from deep-sea sediment metagenomic clone derived Escherichia coli fermentation broth. The structures of new compounds were elucidated by spectroscopic methods. The two new indole alkaloids demonstrated moderately cytotoxic activity against CNE2, Bel7402 and HT1080 cancer cell lines in vitro. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Molecular Response to Toxic Diatom-Derived Aldehydes in the Sea Urchin Paracentrotus lividus

by Stefano Varrella, Giovanna Romano, Adrianna Ianora, Matt G. Bentley, Nadia Ruocco and Maria Costantini

Mar. Drugs 2014, 12(4), 2089-2113; https://doi.org/10.3390/md12042089 - 4 Apr 2014

Cited by 44 | Viewed by 7866

Abstract

Diatoms are dominant photosynthetic organisms in the world’s oceans and represent a major food source for zooplankton and benthic filter-feeders. However, their beneficial role in sustaining marine food webs has been challenged after the discovery that they produce secondary metabolites, such as polyunsaturated [...] Read more.

Diatoms are dominant photosynthetic organisms in the world’s oceans and represent a major food source for zooplankton and benthic filter-feeders. However, their beneficial role in sustaining marine food webs has been challenged after the discovery that they produce secondary metabolites, such as polyunsaturated aldehydes (PUAs), which negatively affect the reproductive success of many invertebrates. Here, we report the effects of two common diatom PUAs, heptadienal and octadienal, which have never been tested before at the molecular level, using the sea urchin, Paracentrotus lividus, as a model organism. We show that both PUAs are able to induce teratogenesis (i.e., malformations), as already reported for decadienal, the better-studied PUA of this group. Moreover, post-recovery experiments show that embryos can recover after treatment with all three PUAs, indicating that negative effects depend both on PUA concentrations and the exposure time of the embryos to these metabolites. We also identify the time range during which PUAs exert the greatest effect on sea urchin embryogenesis. Finally, we report the expression levels of thirty one genes (having a key role in a broad range of functional responses, such as stress, development, differentiation, skeletogenesis and detoxification processes) in order to identify the common targets affected by PUAs and their correlation with morphological abnormalities. This study opens new perspectives for understanding how marine organisms afford protection from environmental toxicants through an integrated network of genes. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Antifouling Activity of Synthetic Alkylpyridinium Polymers Using the Barnacle Model

by Veronica Piazza, Ivanka Dragić, Kristina Sepčić, Marco Faimali, Francesca Garaventa, Tom Turk and Sabina Berne

Mar. Drugs 2014, 12(4), 1959-1976; https://doi.org/10.3390/md12041959 - 2 Apr 2014

Cited by 26 | Viewed by 7407

Abstract

Polymeric alkylpyridinium salts (poly-APS) isolated from the Mediterranean marine sponge, Haliclona (Rhizoniera) sarai, effectively inhibit barnacle larva settlement and natural marine biofilm formation through a non-toxic and reversible mechanism. Potential use of poly-APS-like compounds as antifouling agents led to the chemical synthesis [...] Read more.

Polymeric alkylpyridinium salts (poly-APS) isolated from the Mediterranean marine sponge, Haliclona (Rhizoniera) sarai, effectively inhibit barnacle larva settlement and natural marine biofilm formation through a non-toxic and reversible mechanism. Potential use of poly-APS-like compounds as antifouling agents led to the chemical synthesis of monomeric and oligomeric 3-alkylpyridinium analogues. However, these are less efficient in settlement assays and have greater toxicity than the natural polymers. Recently, a new chemical synthesis method enabled the production of poly-APS analogues with antibacterial, antifungal and anti-acetylcholinesterase activities. The present study examines the antifouling properties and toxicity of six of these synthetic poly-APS using the barnacle (Amphibalanus amphitrite) as a model (cyprids and II stage nauplii larvae) in settlement, acute and sub-acute toxicity assays. Two compounds, APS8 and APS12-3, show antifouling effects very similar to natural poly-APS, with an anti-settlement effective concentration that inhibits 50% of the cyprid population settlement (EC₅₀) after 24 h of 0.32 mg/L and 0.89 mg/L, respectively. The toxicity of APS8 is negligible, while APS12-3 is three-fold more toxic (24-h LC₅₀: nauplii, 11.60 mg/L; cyprids, 61.13 mg/L) than natural poly-APS. This toxicity of APS12-3 towards nauplii is, however, 60-fold and 1200-fold lower than that of the common co-biocides, Zn- and Cu-pyrithione, respectively. Additionally, exposure to APS12-3 for 24 and 48 h inhibits the naupliar swimming ability with respective IC₅₀ of 4.83 and 1.86 mg/L. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Combined Effects of Nitrogen Concentration and Seasonal Changes on the Production of Lipids in Nannochloropsis oculata

by Martin Olofsson, Teresa Lamela, Emmelie Nilsson, Jean-Pascal Bergé, Victória Del Pino, Pauliina Uronen and Catherine Legrand

Mar. Drugs 2014, 12(4), 1891-1910; https://doi.org/10.3390/md12041891 - 31 Mar 2014

Cited by 40 | Viewed by 8382

Abstract

Instead of sole nutrient starvation to boost algal lipid production, we addressed nutrient limitation at two different seasons (autumn and spring) during outdoor cultivation in flat panel photobioreactors. Lipid accumulation, biomass and lipid productivity and changes in fatty acid composition of Nannochloropsis oculata [...] Read more.

Instead of sole nutrient starvation to boost algal lipid production, we addressed nutrient limitation at two different seasons (autumn and spring) during outdoor cultivation in flat panel photobioreactors. Lipid accumulation, biomass and lipid productivity and changes in fatty acid composition of Nannochloropsis oculata were investigated under nitrogen (N) limitation (nitrate:phosphate N:P 5, N:P 2.5 molar ratio). N. oculata was able to maintain a high biomass productivity under N-limitation compared to N-sufficiency (N:P 20) at both seasons, which in spring resulted in nearly double lipid productivity under N-limited conditions (0.21 g L⁻¹ day⁻¹) compared to N-sufficiency (0.11 g L⁻¹ day⁻¹). Saturated and monounsaturated fatty acids increased from 76% to nearly 90% of total fatty acids in N-limited cultures. Higher biomass and lipid productivity in spring could, partly, be explained by higher irradiance, partly by greater harvesting rate (~30%). Our results indicate the potential for the production of algal high value products (i.e., polyunsaturated fatty acids) during both N-sufficiency and N-limitation. To meet the sustainability challenges of algal biomass production, we propose a dual-system process: Closed photobioreactors producing biomass for high value products and inoculum for larger raceway ponds recycling waste/exhaust streams to produce bulk chemicals for fuel, feed and industrial material. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

CS5931, a Novel Polypeptide in Ciona savignyi, Represses Angiogenesis via Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs)

by Ge Liu, Ming Liu, Jianteng Wei, Haijuan Huang, Yuyan Zhang, Jin Zhao, Lin Xiao, Ning Wu, Lanhong Zheng and Xiukun Lin

Mar. Drugs 2014, 12(3), 1530-1544; https://doi.org/10.3390/md12031530 - 13 Mar 2014

Cited by 22 | Viewed by 8273

Abstract

CS5931 is a novel polypeptide from Ciona savignyi with anticancer activities. Previous study in our laboratory has shown that CS5931 can induce cell death via mitochondrial apoptotic pathway. In the present study, we found that the polypeptide could inhibit angiogenesis both in vitro [...] Read more.

CS5931 is a novel polypeptide from Ciona savignyi with anticancer activities. Previous study in our laboratory has shown that CS5931 can induce cell death via mitochondrial apoptotic pathway. In the present study, we found that the polypeptide could inhibit angiogenesis both in vitro and in vivo. CS5931 inhibited the proliferation, migration and formation of capillary-like structures of HUVECs (Human Umbilical Vein Endothelial Cell) in a dose-dependent manner. Additionally, CS5931 repressed spontaneous angiogenesis of the zebrafish vessels. Further studies showed that CS5931 also blocked vascular endothelial growth factor (VEGF) production but without any effect on its mRNA expression. Moreover, CS5931 reduced the expression of matrix metalloproteinases (MMP-2 and MMP-9) both on protein and mRNA levels in HUVEC cells. We demonstrated that CS5931 possessed strong anti-angiogenic activity both in vitro and in vivo, possible via VEGF and MMPs. This study indicates that CS5931 has the potential to be developed as a novel therapeutic agent as an inhibitor of angiogenesis for the treatment of cancer. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Genomic Sequence and Experimental Tractability of a New Decapod Shrimp Model, Neocaridina denticulata

by Nathan J. Kenny, Yung Wa Sin, Xin Shen, Qu Zhe, Wei Wang, Ting Fung Chan, Stephen S. Tobe, Sebastian M. Shimeld, Ka Hou Chu and Jerome H. L. Hui

Mar. Drugs 2014, 12(3), 1419-1437; https://doi.org/10.3390/md12031419 - 11 Mar 2014

Cited by 73 | Viewed by 21446

Abstract

The speciose Crustacea is the largest subphylum of arthropods on the planet after the Insecta. To date, however, the only publically available sequenced crustacean genome is that of the water flea, Daphnia pulex, a member of the Branchiopoda. While Daphnia is a [...] Read more.

The speciose Crustacea is the largest subphylum of arthropods on the planet after the Insecta. To date, however, the only publically available sequenced crustacean genome is that of the water flea, Daphnia pulex, a member of the Branchiopoda. While Daphnia is a well-established ecotoxicological model, previous study showed that one-third of genes contained in its genome are lineage-specific and could not be identified in any other metazoan genomes. To better understand the genomic evolution of crustaceans and arthropods, we have sequenced the genome of a novel shrimp model, Neocaridina denticulata, and tested its experimental malleability. A library of 170-bp nominal fragment size was constructed from DNA of a starved single adult and sequenced using the Illumina HiSeq2000 platform. Core eukaryotic genes, the mitochondrial genome, developmental patterning genes (such as Hox) and microRNA processing pathway genes are all present in this animal, suggesting it has not undergone massive genomic loss. Comparison with the published genome of Daphnia pulex has allowed us to reveal 3750 genes that are indeed specific to the lineage containing malacostracans and branchiopods, rather than Daphnia-specific (E-value: 10⁻⁶). We also show the experimental tractability of N. denticulata, which, together with the genomic resources presented here, make it an ideal model for a wide range of further aquacultural, developmental, ecotoxicological, food safety, genetic, hormonal, physiological and reproductive research, allowing better understanding of the evolution of crustaceans and other arthropods. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Identification of the Major ACE-Inhibitory Peptides Produced by Enzymatic Hydrolysis of a Protein Concentrate from Cuttlefish Wastewater

by Isabel Rodríguez Amado, José Antonio Vázquez, Pilar González, Diego Esteban-Fernández, Mónica Carrera and Carmen Piñeiro

Mar. Drugs 2014, 12(3), 1390-1405; https://doi.org/10.3390/md12031390 - 10 Mar 2014

Cited by 34 | Viewed by 9466

Abstract

The aim of this work was the purification and identification of the major angiotensin converting enzyme (ACE) inhibitory peptides produced by enzymatic hydrolysis of a protein concentrate recovered from a cuttlefish industrial manufacturing effluent. This process consisted on the ultrafiltration of cuttlefish softening [...] Read more.

The aim of this work was the purification and identification of the major angiotensin converting enzyme (ACE) inhibitory peptides produced by enzymatic hydrolysis of a protein concentrate recovered from a cuttlefish industrial manufacturing effluent. This process consisted on the ultrafiltration of cuttlefish softening wastewater, with a 10 kDa cut-off membrane, followed by the hydrolysis with alcalase of the retained fraction. Alcalase produced ACE inhibitors reaching the highest activity (IC₅₀ = 76.8 ± 15.2 μg mL⁻¹) after 8 h of proteolysis. Sequential ultrafiltration of the 8 h hydrolysate with molecular weight cut-off (MWCO) membranes of 10 and 1 kDa resulted in the increased activity of each permeate, with a final IC₅₀ value of 58.4 ± 4.6 μg mL⁻¹. Permeate containing peptides lower than 1 kDa was separated by reversed-phase high performance liquid chromatography (RP-HPLC). Four fractions (A–D) with potent ACE inhibitory activity were isolated and their main peptides identified using high performance liquid chromatography coupled to an electrospray ion trap Fourier transform ion cyclotron resonance-mass spectrometer (HPLC-ESI-IT-FTICR) followed by comparison with databases and de novo sequencing. The amino acid sequences of the identified peptides contained at least one hydrophobic and/or a proline together with positively charged residues in at least one of the three C-terminal positions. The IC₅₀ values of the fractions ranged from 1.92 to 8.83 μg mL⁻¹, however this study fails to identify which of these peptides are ultimately responsible for the potent antihypertensive activity of these fractions. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Rapid and Accurate Identification by Real-Time PCR of Biotoxin-Producing Dinoflagellates from the Family Gymnodiniaceae

by Kirsty F. Smith, Miguel De Salas, Janet Adamson and Lesley L. Rhodes

Mar. Drugs 2014, 12(3), 1361-1376; https://doi.org/10.3390/md12031361 - 7 Mar 2014

Cited by 29 | Viewed by 9694

Abstract

The identification of toxin-producing dinoflagellates for monitoring programmes and bio-compound discovery requires considerable taxonomic expertise. It can also be difficult to morphologically differentiate toxic and non-toxic species or strains. Various molecular methods have been used for dinoflagellate identification and detection, and this study [...] Read more.

The identification of toxin-producing dinoflagellates for monitoring programmes and bio-compound discovery requires considerable taxonomic expertise. It can also be difficult to morphologically differentiate toxic and non-toxic species or strains. Various molecular methods have been used for dinoflagellate identification and detection, and this study describes the development of eight real-time polymerase chain reaction (PCR) assays targeting the large subunit ribosomal RNA (LSU rRNA) gene of species from the genera Gymnodinium, Karenia, Karlodinium, and Takayama. Assays proved to be highly specific and sensitive, and the assay for G. catenatum was further developed for quantification in response to a bloom in Manukau Harbour, New Zealand. The assay estimated cell densities from environmental samples as low as 0.07 cells per PCR reaction, which equated to three cells per litre. This assay not only enabled conclusive species identification but also detected the presence of cells below the limit of detection for light microscopy. This study demonstrates the usefulness of real-time PCR as a sensitive and rapid molecular technique for the detection and quantification of micro-algae from environmental samples. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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A Novel Lipid Extraction Method from Wet Microalga Picochlorum sp. at Room Temperature

by Fangfang Yang, Wenzhou Xiang, Xiumei Sun, Hualian Wu, Tao Li and Lijuan Long

Mar. Drugs 2014, 12(3), 1258-1270; https://doi.org/10.3390/md12031258 - 6 Mar 2014

Cited by 81 | Viewed by 13908

Abstract

A novel method using ethanol was proposed for extracting lipids from wet microalga Picochlorum sp. at room temperature and pressure. In this study, Central Composite design (CCD) was applied to investigate the optimum conditions of lipid extraction. The results revealed that the solvent [...] Read more.

A novel method using ethanol was proposed for extracting lipids from wet microalga Picochlorum sp. at room temperature and pressure. In this study, Central Composite design (CCD) was applied to investigate the optimum conditions of lipid extraction. The results revealed that the solvent to biomass ratio had the largest effect on lipid extraction efficiency, followed by extraction time and temperature. A high lipid extraction yield (33.04% of the dry weight) was obtained under the following extraction conditions: 5 mL solvents per gram of wet biomass for 37 min with gentle stirring at room temperature. The extraction yield was comparable to that obtained by the widely used Bligh-Dyer method. Furthermore, no significant differences in the distribution of lipid classes and fatty acid composition were observed according to different extraction methods. In conclusion, these results indicated that the proposed procedure using ethanol could extract lipids from wet biomass efficiently and had giant potential for lipid extraction at large scale. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Optimization of Medium Using Response Surface Methodology for Lipid Production by Scenedesmus sp.

by Fangfang Yang, Lijuan Long, Xiumei Sun, Hualian Wu, Tao Li and Wenzhou Xiang

Mar. Drugs 2014, 12(3), 1245-1257; https://doi.org/10.3390/md12031245 - 6 Mar 2014

Cited by 80 | Viewed by 9998

Abstract

Lipid production is an important indicator for assessing microalgal species for biodiesel production. In this work, the effects of medium composition on lipid production by Scenedesmus sp. were investigated using the response surface methodology. The results of a Plackett–Burman design experiment revealed that [...] Read more.

Lipid production is an important indicator for assessing microalgal species for biodiesel production. In this work, the effects of medium composition on lipid production by Scenedesmus sp. were investigated using the response surface methodology. The results of a Plackett–Burman design experiment revealed that NaHCO₃, NaH₂PO₄·2H₂O and NaNO₃ were three factors significantly influencing lipid production, which were further optimized by a Box–Behnken design. The optimal medium was found to contain 3.07 g L⁻¹ NaHCO₃, 15.49 mg L⁻¹ NaH₂PO₄·2H₂O and 803.21 mg L⁻¹ NaNO₃. Using the optimal conditions previously determined, the lipid production (304.02 mg·L⁻¹) increased 54.64% more than that using the initial medium, which agreed well with the predicted value 309.50 mg L⁻¹. Additionally, lipid analysis found that palmitic acid (C16:0) and oleic acid (C18:1) dominantly constituted the algal fatty acids (about 60% of the total fatty acids) and a much higher content of neutral lipid accounted for 82.32% of total lipids, which strongly proved that Scenedesmus sp. is a very promising feedstock for biodiesel production. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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The Marine Sponge-Derived Inorganic Polymers, Biosilica and Polyphosphate, as Morphogenetically Active Matrices/Scaffolds for the Differentiation of Human Multipotent Stromal Cells: Potential Application in 3D Printing and Distraction Osteogenesis

by Xiaohong Wang, Heinz C. Schröder, Vladislav Grebenjuk, Bärbel Diehl-Seifert, Volker Mailänder, Renate Steffen, Ute Schloßmacher and Werner E. G. Müller

Mar. Drugs 2014, 12(2), 1131-1147; https://doi.org/10.3390/md12021131 - 21 Feb 2014

Cited by 51 | Viewed by 14712

Abstract

The two marine inorganic polymers, biosilica (BS), enzymatically synthesized from ortho-silicate, and polyphosphate (polyP), a likewise enzymatically synthesized polymer consisting of 10 to >100 phosphate residues linked by high-energy phosphoanhydride bonds, have previously been shown to display a morphogenetic effect on osteoblasts. In [...] Read more.

The two marine inorganic polymers, biosilica (BS), enzymatically synthesized from ortho-silicate, and polyphosphate (polyP), a likewise enzymatically synthesized polymer consisting of 10 to >100 phosphate residues linked by high-energy phosphoanhydride bonds, have previously been shown to display a morphogenetic effect on osteoblasts. In the present study, the effect of these polymers on the differential differentiation of human multipotent stromal cells (hMSC), mesenchymal stem cells, that had been encapsulated into beads of the biocompatible plant polymer alginate, was studied. The differentiation of the hMSCs in the alginate beads was directed either to the osteogenic cell lineage by exposure to an osteogenic medium (mineralization activation cocktail; differentiation into osteoblasts) or to the chondrogenic cell lineage by incubating in chondrocyte differentiation medium (triggering chondrocyte maturation). Both biosilica and polyP, applied as Ca²⁺ salts, were found to induce an increased mineralization in osteogenic cells; these inorganic polymers display also morphogenetic potential. The effects were substantiated by gene expression studies, which revealed that biosilica and polyP strongly and significantly increase the expression of bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP) in osteogenic cells, which was significantly more pronounced in osteogenic versus chondrogenic cells. A differential effect of the two polymers was seen on the expression of the two collagen types, I and II. While collagen Type I is highly expressed in osteogenic cells, but not in chondrogenic cells after exposure to biosilica or polyP, the upregulation of the steady-state level of collagen Type II transcripts in chondrogenic cells is comparably stronger than in osteogenic cells. It is concluded that the two polymers, biosilica and polyP, are morphogenetically active additives for the otherwise biologically inert alginate polymer. It is proposed that alginate, supplemented with polyP and/or biosilica, is a suitable biomaterial that promotes the growth and differentiation of hMSCs and might be beneficial for application in 3D tissue printing of hMSCs and for the delivery of hMSCs in fractures, surgically created during distraction osteogenesis. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Mode of Action of Diterpene and Characterization of Related Metabolites from the Soft Coral, Xenia elongata

by Eric H. Andrianasolo, Liti Haramaty, Eileen White, Richard Lutz and Paul Falkowski

Mar. Drugs 2014, 12(2), 1102-1115; https://doi.org/10.3390/md12021102 - 20 Feb 2014

Cited by 19 | Viewed by 9093

Abstract

Chemical and biological investigation of the cultured marine soft coral Xenia elongata led to the isolation of two new diterpenes (2, 3). Their structures were elucidated using a combination of NMR and mass spectrometry. Biological evaluations and assessments were determined [...] Read more.

Chemical and biological investigation of the cultured marine soft coral Xenia elongata led to the isolation of two new diterpenes (2, 3). Their structures were elucidated using a combination of NMR and mass spectrometry. Biological evaluations and assessments were determined using the specific apoptosis induction assay based on genetically engineered mammalian cell line D3 deficient in Bak and Bax and derived from a mouse epithelial cell. The diterpenes induce apoptosis in low micromolar concentrations. The results indicate that the previously isolated compound (1) affects cell in a manner similar to that of HSP90 and HDAC inhibitors and in a manner opposite of PI3 kinase/mTOR inhibitors. Compound (3) inhibits selectively HDAC6 in high micromolar concentrations. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Solwaric Acids A and B, Antibacterial Aromatic Acids from a Marine Solwaraspora sp.

by Gregory A. Ellis, Thomas P. Wyche, Charles G. Fry, Doug R. Braun and Tim S. Bugni

Mar. Drugs 2014, 12(2), 1013-1022; https://doi.org/10.3390/md12021013 - 14 Feb 2014

Cited by 28 | Viewed by 8296

Abstract

Two novel trialkyl-substituted aromatic acids, solwaric acids A and B, were isolated from a marine Solwaraspora sp. cultivated from the ascidian Trididemnum orbiculatum. Solwaric acids A and B were isotopically labeled with U-¹³C glucose, and analysis of a ¹³C– [...] Read more.

Two novel trialkyl-substituted aromatic acids, solwaric acids A and B, were isolated from a marine Solwaraspora sp. cultivated from the ascidian Trididemnum orbiculatum. Solwaric acids A and B were isotopically labeled with U-¹³C glucose, and analysis of a ¹³C–¹³C COSY allowed for unambiguous determination of the location of the phenyl methyl group. The two novel compounds demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Hyaluromycin, a New Hyaluronidase Inhibitor of Polyketide Origin from Marine Streptomyces sp.

by Enjuro Harunari, Chiaki Imada, Yasuhiro Igarashi, Takao Fukuda, Takeshi Terahara and Takeshi Kobayashi

Mar. Drugs 2014, 12(1), 491-507; https://doi.org/10.3390/md12010491 - 21 Jan 2014

Cited by 36 | Viewed by 13529

Abstract

Hyaluromycin (1), a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derived Streptomyces sp. as a HAase inhibitor on the basis of HAase activity screening. The structure of 1 was elucidated through the [...] Read more.

Hyaluromycin (1), a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derived Streptomyces sp. as a HAase inhibitor on the basis of HAase activity screening. The structure of 1 was elucidated through the interpretation of NMR data for the compound and its 3″-O-methyl derivative in combination with an incorporation experiment with [1,2-¹³C₂]acetate. The compound’s absolute configuration was determined by the comparison of its circular dichroism (CD) spectrum with those of other rubromycins. Hyaluromycin (1) consists of a γ-rubromycin core structure possessing a 2-amino-3-hydroxycyclopent-2-enone (C₅N) unit as an amide substituent of the carboxyl function; both structural units have been reported only from actinomycetes. Hyaluromycin (1) displayed approximately 25-fold more potent hyaluronidase inhibitory activity against hyaluronidase than did glycyrrhizin, a known inhibitor of plant origin. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Identification and Biochemical Characterization of Halisulfate 3 and Suvanine as Novel Inhibitors of Hepatitis C Virus NS3 Helicase from a Marine Sponge

by Atsushi Furuta, Kazi Abdus Salam, Idam Hermawan, Nobuyoshi Akimitsu, Junichi Tanaka, Hidenori Tani, Atsuya Yamashita, Kohji Moriishi, Masamichi Nakakoshi, Masayoshi Tsubuki, Poh Wee Peng, Youichi Suzuki, Naoki Yamamoto, Yuji Sekiguchi, Satoshi Tsuneda and Naohiro Noda

Mar. Drugs 2014, 12(1), 462-476; https://doi.org/10.3390/md12010462 - 21 Jan 2014

Cited by 13 | Viewed by 9113

Abstract

Hepatitis C virus (HCV) is an important etiological agent that is responsible for the development of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV nonstructural protein 3 (NS3) helicase is a possible target for novel drug development due to its essential role in [...] Read more.

Hepatitis C virus (HCV) is an important etiological agent that is responsible for the development of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV nonstructural protein 3 (NS3) helicase is a possible target for novel drug development due to its essential role in viral replication. In this study, we identified halisulfate 3 (hal3) and suvanine as novel NS3 helicase inhibitors, with IC₅₀ values of 4 and 3 µM, respectively, from a marine sponge by screening extracts of marine organisms. Both hal3 and suvanine inhibited the ATPase, RNA binding, and serine protease activities of NS3 helicase with IC₅₀ values of 8, 8, and 14 µM, and 7, 3, and 34 µM, respectively. However, the dengue virus (DENV) NS3 helicase, which shares a catalytic core (consisting mainly of ATPase and RNA binding sites) with HCV NS3 helicase, was not inhibited by hal3 and suvanine, even at concentrations of 100 µM. Therefore, we conclude that hal3 and suvanine specifically inhibit HCV NS3 helicase via an interaction with an allosteric site in NS3 rather than binding to the catalytic core. This led to the inhibition of all NS3 activities, presumably by inducing conformational changes. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Chitosan-Alginate Biocomposite Containing Fucoidan for Bone Tissue Engineering

by Jayachandran Venkatesan, Ira Bhatnagar and Se-Kwon Kim

Mar. Drugs 2014, 12(1), 300-316; https://doi.org/10.3390/md12010300 - 16 Jan 2014

Cited by 246 | Viewed by 15317

Abstract

Over the last few years, significant research has been conducted in the construction of artificial bone scaffolds. In the present study, different types of polymer scaffolds, such as chitosan-alginate (Chi-Alg) and chitosan-alginate with fucoidan (Chi-Alg-fucoidan), were developed by a freeze-drying method, and each [...] Read more.

Over the last few years, significant research has been conducted in the construction of artificial bone scaffolds. In the present study, different types of polymer scaffolds, such as chitosan-alginate (Chi-Alg) and chitosan-alginate with fucoidan (Chi-Alg-fucoidan), were developed by a freeze-drying method, and each was characterized as a bone graft substitute. The porosity, water uptake and retention ability of the prepared scaffolds showed similar efficacy. The pore size of the Chi-Alg and Chi-Alg-fucoidan scaffolds were measured from scanning electron microscopy and found to be 62–490 and 56–437 µm, respectively. In vitro studies using the MG-63 cell line revealed profound cytocompatibility, increased cell proliferation and enhanced alkaline phosphatase secretion in the Chi-Alg-fucoidan scaffold compared to the Chi-Alg scaffold. Further, protein adsorption and mineralization were about two times greater in the Chi-Alg-fucoidan scaffold than the Chi-Alg scaffold. Hence, we suggest that Chi-Alg-fucoidan will be a promising biomaterial for bone tissue regeneration. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Eight New Peptaibols from Sponge-Associated Trichoderma atroviride

by Irina Panizel, Oded Yarden, Micha Ilan and Shmuel Carmeli

Mar. Drugs 2013, 11(12), 4937-4960; https://doi.org/10.3390/md11124937 - 11 Dec 2013

Cited by 35 | Viewed by 8017

Abstract

Eight new and four known peptaibols were isolated from a strain of the fungus, Trichoderma atroviride (NF16), which was cultured from an Axinellid sponge collected from the East Mediterranean coast of Israel. The structures of the pure compounds were determined using HRMS, MS/MS [...] Read more.

Eight new and four known peptaibols were isolated from a strain of the fungus, Trichoderma atroviride (NF16), which was cultured from an Axinellid sponge collected from the East Mediterranean coast of Israel. The structures of the pure compounds were determined using HRMS, MS/MS and one- and two-dimensional NMR measurements. The isolated compounds belong to the trichorzianines, a family of 19-residue linear hydrophobic peptides containing a high proportion of α-aminoisobutyric acid (Aib), an acetylated N-terminus and a C-terminal amino alcohol. These new peptaibols exhibited antimicrobial activity against environmental bacteria isolated from the Mediterranean coast of Israel. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Identification of Two Novel Anti-Fibrotic Benzopyran Compounds Produced by Engineered Strains Derived from Streptomyces xiamenensis M1-94P that Originated from Deep-Sea Sediments

by Zhong-Yuan You, Ya-Hui Wang, Zhi-Gang Zhang, Min-Juan Xu, Shu-Jie Xie, Tie-Sheng Han, Lei Feng, Xue-Gong Li and Jun Xu

Mar. Drugs 2013, 11(10), 4035-4049; https://doi.org/10.3390/md11104035 - 22 Oct 2013

Cited by 14 | Viewed by 7468

Abstract

The benzopyran compound obtained by cultivating a mangrove-derived strain, Streptomyces xiamenensis strain 318, shows multiple biological effects, including anti-fibrotic and anti-hypertrophic scar properties. To increase the diversity in the structures of the available benzopyrans, by means of biosynthesis, the strain was screened for [...] Read more.

The benzopyran compound obtained by cultivating a mangrove-derived strain, Streptomyces xiamenensis strain 318, shows multiple biological effects, including anti-fibrotic and anti-hypertrophic scar properties. To increase the diversity in the structures of the available benzopyrans, by means of biosynthesis, the strain was screened for spontaneous rifampicin resistance (Rif), and a mutated rpsL gene to confer streptomycin resistance (Str), was introduced into the S. xiamenensis strain M1-94P that originated from deep-sea sediments. Two new benzopyran derivatives, named xiamenmycin C (1) and D (2), were isolated from the crude extracts of a selected Str-Rif double mutant (M6) of M1-94P. The structures of 1 and 2 were identified by analyzing extensive spectroscopic data. Compounds 1 and 2 both inhibit the proliferation of human lung fibroblasts (WI26), and 1 exhibits better anti-fibrotic activity than xiamenmycin. Our study presents the novel bioactive compounds isolated from S. xiamenensis mutant strain M6 constructed by ribosome engineering, which could be a useful approach in the discovery of new anti-fibrotic compounds. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Enhanced Anti-Obesity Activities of Red Mold Dioscorea When Fermented Using Deep Ocean Water as the Culture Water

by Li-Chun Wang, Tzu-Ying Lung, Yi-Hsin Kung, Jyh-Jye Wang, Tsung-Yu Tsai, Bai-Luh Wei, Tzu-Ming Pan and Chun-Lin Lee

Mar. Drugs 2013, 11(10), 3902-3925; https://doi.org/10.3390/md11103902 - 15 Oct 2013

Cited by 21 | Viewed by 8291

Abstract

Deep ocean water (DOW) has, in previous studies, been found to be a novel anti-obesity drink and useful in raising Monascus-produced monascin and ankaflavin levels. This may resolve the limited anti-obesity ability of red mold dioscorea (RMD) known as the Monascus purpureus [...] Read more.

Deep ocean water (DOW) has, in previous studies, been found to be a novel anti-obesity drink and useful in raising Monascus-produced monascin and ankaflavin levels. This may resolve the limited anti-obesity ability of red mold dioscorea (RMD) known as the Monascus purpureus-fermented Disocorea batatas. This study aims to compare the anti-obesity effect of DOW-cultured RMD (DOW-RMD) and ultra-pure water-cultured RMD (UPW-RMD) in rats fed on a high fat diet. Moreover, the effect of ions composition of DOW and DOW-influenced functional metabolites change of RMD on the differentiation and lipogenesis regulation were investigated using 3T3-L1 pre-adipocytes. In the animal test, compared to UPW-RMD, DOW-RMD possessed better ability to inhibit increases in weight gain, and better feed efficiency, body-fat pad and cross-sectional area of adipocytes. In the cell test, the anti-obesity abilities of DOW-RMD in inhibiting PPARγ and C/EBPα expression in differentiation and lipoprotein lipase activity in lipogenesis were contributed to by the DOW-increased monascin and ankaflavin levels and the ions of DOW, respectively. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Harnessing the Potential of Halogenated Natural Product Biosynthesis by Mangrove-Derived Actinomycetes

by Xue-Gong Li, Xiao-Min Tang, Jing Xiao, Guang-Hui Ma, Li Xu, Shu-Jie Xie, Min-Juan Xu, Xiang Xiao and Jun Xu

Mar. Drugs 2013, 11(10), 3875-3890; https://doi.org/10.3390/md11103875 - 14 Oct 2013

Cited by 16 | Viewed by 8028

Abstract

Mangrove-derived actinomycetes are promising sources of bioactive natural products. In this study, using homologous screening of the biosynthetic genes and anti-microorganism/tumor assaying, 163 strains of actinomycetes isolated from mangrove sediments were investigated for their potential to produce halogenated metabolites. The FADH₂-dependent [...] Read more.

Mangrove-derived actinomycetes are promising sources of bioactive natural products. In this study, using homologous screening of the biosynthetic genes and anti-microorganism/tumor assaying, 163 strains of actinomycetes isolated from mangrove sediments were investigated for their potential to produce halogenated metabolites. The FADH₂-dependent halogenase genes, identified in PCR-screening, were clustered in distinct clades in the phylogenetic analysis. The coexistence of either polyketide synthase (PKS) or nonribosomal peptide synthetase (NRPS) as the backbone synthetases in the strains harboring the halogenase indicated that these strains had the potential to produce structurally diversified antibiotics. As a validation, a new enduracidin producer, Streptomyces atrovirens MGR140, was identified and confirmed by gene disruption and HPLC analysis. Moreover, a putative ansamycin biosynthesis gene cluster was detected in Streptomyces albogriseolus MGR072. Our results highlight that combined genome mining is an efficient technique to tap promising sources of halogenated natural products synthesized by mangrove-derived actinomycetes. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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The Red Seaweed Gracilaria gracilis as a Multi Products Source

by Matteo Francavilla, Massimo Franchi, Massimo Monteleone and Carmela Caroppo

Mar. Drugs 2013, 11(10), 3754-3776; https://doi.org/10.3390/md11103754 - 30 Sep 2013

Cited by 205 | Viewed by 15875

Abstract

In recent years seaweeds have increasingly attracted interest in the search for new drugs and have been shown to be a primary source of bioactive natural compounds and biomaterials. In the present investigation, the biochemical composition of the red seaweed Gracilaria gracilis, [...] Read more.

In recent years seaweeds have increasingly attracted interest in the search for new drugs and have been shown to be a primary source of bioactive natural compounds and biomaterials. In the present investigation, the biochemical composition of the red seaweed Gracilaria gracilis, collected seasonally in the Lesina Lagoon (Southern Adriatic Sea, Lesina, Italy), was assayed by means of advanced analytical techniques, such as gas-chromatography coupled with mass spectrometry and spectrophotometric tests. In particular, analysis of lipids, fatty acids, sterols, proteins, phycobiliproteins and carbohydrates as well as phenolic content, antioxidant and radical scavenging activity were performed. In winter extracts of G. gracilis, a high content of R-phycoerythrin together with other valuable products such as arachidonic acid (PUFA ω-6), proteins and carbohydrates was observed. High antioxidant and radical scavenging activities were also detected in summer extracts of the seaweed together with a high content of total phenols. In conclusion, this study points out the possibility of using Gracilaria gracilis as a multi products source for biotechnological, nutraceutical and pharmaceutical applications even although more investigations are required for separating, purifying and characterizing these bioactive compounds. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Review

Jump to: Research

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Open AccessReview

Marine Invertebrate Xenobiotic-Activated Nuclear Receptors: Their Application as Sensor Elements in High-Throughput Bioassays for Marine Bioactive Compounds

by Ingrid Richter and Andrew E. Fidler

Mar. Drugs 2014, 12(11), 5590-5618; https://doi.org/10.3390/md12115590 - 24 Nov 2014

Cited by 11 | Viewed by 9756

Abstract

Developing high-throughput assays to screen marine extracts for bioactive compounds presents both conceptual and technical challenges. One major challenge is to develop assays that have well-grounded ecological and evolutionary rationales. In this review we propose that a specific group of ligand-activated transcription factors [...] Read more.

Developing high-throughput assays to screen marine extracts for bioactive compounds presents both conceptual and technical challenges. One major challenge is to develop assays that have well-grounded ecological and evolutionary rationales. In this review we propose that a specific group of ligand-activated transcription factors are particularly well-suited to act as sensors in such bioassays. More specifically, xenobiotic-activated nuclear receptors (XANRs) regulate transcription of genes involved in xenobiotic detoxification. XANR ligand-binding domains (LBDs) may adaptively evolve to bind those bioactive, and potentially toxic, compounds to which organisms are normally exposed to through their specific diets. A brief overview of the function and taxonomic distribution of both vertebrate and invertebrate XANRs is first provided. Proof-of-concept experiments are then described which confirm that a filter-feeding marine invertebrate XANR LBD is activated by marine bioactive compounds. We speculate that increasing access to marine invertebrate genome sequence data, in combination with the expression of functional recombinant marine invertebrate XANR LBDs, will facilitate the generation of high-throughput bioassays/biosensors of widely differing specificities, but all based on activation of XANR LBDs. Such assays may find application in screening marine extracts for bioactive compounds that could act as drug lead compounds. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Marine Sponge Derived Natural Products between 2001 and 2010: Trends and Opportunities for Discovery of Bioactives

by Mohammad Ferdous Mehbub, Jie Lei, Christopher Franco and Wei Zhang

Mar. Drugs 2014, 12(8), 4539-4577; https://doi.org/10.3390/md12084539 - 19 Aug 2014

Cited by 342 | Viewed by 24424

Abstract

Marine sponges belonging to the phylum Porifera (Metazoa), evolutionarily the oldest animals are the single best source of marine natural products. The present review presents a comprehensive overview of the source, taxonomy, country of origin or geographical position, chemical class, and biological activity [...] Read more.

Marine sponges belonging to the phylum Porifera (Metazoa), evolutionarily the oldest animals are the single best source of marine natural products. The present review presents a comprehensive overview of the source, taxonomy, country of origin or geographical position, chemical class, and biological activity of sponge-derived new natural products discovered between 2001 and 2010. The data has been analyzed with a view to gaining an outlook on the future trends and opportunities in the search for new compounds and their sources from marine sponges. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Marine Microorganism-Invertebrate Assemblages: Perspectives to Solve the “Supply Problem” in the Initial Steps of Drug Discovery

by Miguel Costa Leal, Christopher Sheridan, Ronald Osinga, Gisela Dionísio, Rui Jorge Miranda Rocha, Bruna Silva, Rui Rosa and Ricardo Calado

Mar. Drugs 2014, 12(7), 3929-3952; https://doi.org/10.3390/md12073929 - 30 Jun 2014

Cited by 70 | Viewed by 12878

Abstract

The chemical diversity associated with marine natural products (MNP) is unanimously acknowledged as the “blue gold” in the urgent quest for new drugs. Consequently, a significant increase in the discovery of MNP published in the literature has been observed in the past decades, [...] Read more.

The chemical diversity associated with marine natural products (MNP) is unanimously acknowledged as the “blue gold” in the urgent quest for new drugs. Consequently, a significant increase in the discovery of MNP published in the literature has been observed in the past decades, particularly from marine invertebrates. However, it remains unclear whether target metabolites originate from the marine invertebrates themselves or from their microbial symbionts. This issue underlines critical challenges associated with the lack of biomass required to supply the early stages of the drug discovery pipeline. The present review discusses potential solutions for such challenges, with particular emphasis on innovative approaches to culture invertebrate holobionts (microorganism-invertebrate assemblages) through in toto aquaculture, together with methods for the discovery and initial production of bioactive compounds from these microbial symbionts. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Emerging Strategies and Integrated Systems Microbiology Technologies for Biodiscovery of Marine Bioactive Compounds

by Javier Rocha-Martin, Catriona Harrington, Alan D.W. Dobson and Fergal O'Gara

Mar. Drugs 2014, 12(6), 3516-3559; https://doi.org/10.3390/md12063516 - 10 Jun 2014

Cited by 61 | Viewed by 16371

Abstract

Marine microorganisms continue to be a source of structurally and biologically novel compounds with potential use in the biotechnology industry. The unique physiochemical properties of the marine environment (such as pH, pressure, temperature, osmolarity) and uncommon functional groups (such as isonitrile, dichloroimine, isocyanate, [...] Read more.

Marine microorganisms continue to be a source of structurally and biologically novel compounds with potential use in the biotechnology industry. The unique physiochemical properties of the marine environment (such as pH, pressure, temperature, osmolarity) and uncommon functional groups (such as isonitrile, dichloroimine, isocyanate, and halogenated functional groups) are frequently found in marine metabolites. These facts have resulted in the production of bioactive substances with different properties than those found in terrestrial habitats. In fact, the marine environment contains a relatively untapped reservoir of bioactivity. Recent advances in genomics, metagenomics, proteomics, combinatorial biosynthesis, synthetic biology, screening methods, expression systems, bioinformatics, and the ever increasing availability of sequenced genomes provides us with more opportunities than ever in the discovery of novel bioactive compounds and biocatalysts. The combination of these advanced techniques with traditional techniques, together with the use of dereplication strategies to eliminate known compounds, provides a powerful tool in the discovery of novel marine bioactive compounds. This review outlines and discusses the emerging strategies for the biodiscovery of these bioactive compounds. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Quorum Quenching Agents: Resources for Antivirulence Therapy

by Kaihao Tang and Xiao-Hua Zhang

Mar. Drugs 2014, 12(6), 3245-3282; https://doi.org/10.3390/md12063245 - 30 May 2014

Cited by 131 | Viewed by 19174

Abstract

The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which [...] Read more.

The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ) agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Tipping Points in Seaweed Genetic Engineering: Scaling Up Opportunities in the Next Decade

by Hanzhi Lin and Song Qin

Mar. Drugs 2014, 12(5), 3025-3045; https://doi.org/10.3390/md12053025 - 22 May 2014

Cited by 23 | Viewed by 13908

Abstract

Seaweed genetic engineering is a transgenic expression system with unique features compared with those of heterotrophic prokaryotes and higher plants. This study discusses several newly sequenced seaweed nuclear genomes and the necessity that research on vector design should consider endogenous promoters, codon optimization, [...] Read more.

Seaweed genetic engineering is a transgenic expression system with unique features compared with those of heterotrophic prokaryotes and higher plants. This study discusses several newly sequenced seaweed nuclear genomes and the necessity that research on vector design should consider endogenous promoters, codon optimization, and gene copy number. Seaweed viruses and artificial transposons can be applied as transformation methods after acquiring a comprehensive understanding of the mechanism of viral infections in seaweeds and transposon patterns in seaweed genomes. After cultivating transgenic algal cells and tissues in a photobioreactor, a biosafety assessment of genetically modified (GM) seaweeds must be conducted before open-sea application. We propose a set of programs for the evaluation of gene flow from GM seaweeds to local/geographical environments. The effective implementation of such programs requires fundamentally systematic and interdisciplinary studies on algal physiology and genetics, marine hydrology, reproductive biology, and ecology. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Bioactive Marine Drugs and Marine Biomaterials for Brain Diseases

by Clara Grosso, Patrícia Valentão, Federico Ferreres and Paula B. Andrade

Mar. Drugs 2014, 12(5), 2539-2589; https://doi.org/10.3390/md12052539 - 2 May 2014

Cited by 31 | Viewed by 11668

Abstract

Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, some [...] Read more.

Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, some examples of neuroprotective drugs and neurotoxins will be discussed. Their role in neuroscience research and development of new therapies targeting the central nervous system will be addressed, with particular focus on neuroinflammation and neurodegeneration. In addition, the neuronal growth promoted by marine drugs, as well as the recent advances in neural tissue engineering, will be highlighted. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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