Romano G , Almeida M , Varela Coelho A , Cutignano A , Gonçalves LG , Hansen E , Khnykin D , Mass T , Ramšak A , Rocha MS , Silva TH , Sugni M , Ballarin L , Genevière AM .

16203 European Cooperation in Science and Technology

	Figure 1. The demosponge Smenospongia aurea (left) and Aplysina fistularis (right). Photo by Joseph Pawlik (https://spongeguide.uncw.edu/, accessed on 13 February 2022).
	Figure 2. Proportion of different bioactivity associated to sponge-derived MNP, according to data in Table S1.
	Figure 3. Renieramycin E (1) and ecteinascidin-743 (2).
	Figure 4. Smenamide A; (3) smenamide B (4).
	Figure 5. Aplysinopsin.
	Figure 6. Proportion of different bioactivity associated to cnidarian-derived MNP, according to data in Table S2.
	Figure 7. Fuscoside E (6); 11-epi-sinulariolide acetate (7); sarcophine (8); pukalide (9); cladidiol (10).
	Figure 8. Protoxenicin A (11); sinularone I (12).
	Figure 9. Proportion of different bioactivity associated to mollusc-derived MNP, according to data in Table S3.
	Figure 10. Lignarenone B (13) and dolastatin 10 (14).
	Figure 11. The sea hare Dolabella auricularia. (Photo by Dr. Ernesto Mollo.)
	Figure 12. The gastropod Conus textile. (Courtesy of Dr. Ernesto Mollo.)
	Figure 13. The sea urchin Paracentrotus lividus (left) and the sea star Echinaster sepositus (right) (photo by Federico Betti).
	Figure 14. Proportion of different bioactivity associated to echinoderm-derived MNPs, according to data in Table S4.
	Figure 15. Echinochrome A (15); spinochrome E (16).
	Figure 16. The ascidians Ciona intestinalis (left) and Botryllus schlosseri (right).
	Figure 17. Proportion of different bioactivity associated to tunicate-derived MNP, according to data in Table S5.
	Figure 18. Didemnin B (17) and plitidepsin (18).
	Figure 19. Metabolomics workflow for marine biodiscovery.
	Figure 20. Number of papers using metabolomic approaches in marine invertebrates by year (search was performed on March 2021 in PubMed limited to original papers that mention (((metabolomic OR “metabolic profile”) AND (“marine invertebrate” OR echinoderm OR cnidarian OR mollusc OR sponge OR tunicate))) or (((metabolomic OR “metabolic profile”) AND (“NMR” OR “Nuclear Magnetic Resonance”) AND (“marine invertebrate” OR echinoderm OR cnidarian OR mollusc OR sponge OR tunicate))) or (((metabolomic OR “metabolic profile”) AND (“mass spectrometry” OR “LC-MS” OR “GC-MS” OR “MS”) AND (“marine invertebrate” OR echinoderm OR cnidarian OR mollusc OR sponge OR tunicate))) in the title, abstract or keyword).

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Chollet, Fucoidans in Nanomedicine. 2016, Pubmed , Echinobase
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Cruz, On the Mechanism of Action of Dragmacidins I and J, Two New Representatives of a New Class of Protein Phosphatase 1 and 2A Inhibitors. 2018, Pubmed
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Cutignano, Development and Application of a Novel SPE-Method for Bioassay-Guided Fractionation of Marine Extracts. 2015, Pubmed
D'Ambra, A Review of Toxins from Cnidaria. 2020, Pubmed
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Demeyer, Inter- and intra-organ spatial distributions of sea star saponins by MALDI imaging. 2015, Pubmed , Echinobase
Domingues, The potential of cellulose nanocrystals in tissue engineering strategies. 2014, Pubmed
Dona, Precision high-throughput proton NMR spectroscopy of human urine, serum, and plasma for large-scale metabolic phenotyping. 2014, Pubmed
Dou, Origins and Bioactivities of Natural Compounds Derived from Marine Ascidians and Their Symbionts. 2019, Pubmed
Dugan, Oriented surfaces of adsorbed cellulose nanowhiskers promote skeletal muscle myogenesis. 2013, Pubmed
Dunlop, Towards the scalable isolation of cellulose nanocrystals from tunicates. 2020, Pubmed
Dutertre, Deep venomics reveals the mechanism for expanded peptide diversity in cone snail venom. 2013, Pubmed
Dwivedi, Marine Antithrombotics. 2020, Pubmed
Ehrlich, Discovery of chitin in skeletons of non-verongiid Red Sea demosponges. 2018, Pubmed
Ehrlich, Arrested in Glass: Actin within Sophisticated Architectures of Biosilica in Sponges. 2022, Pubmed
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Elsayed, Metabolomic profiling and biological investigation of the marine sponge-derived bacterium Rhodococcus sp. UA13. 2018, Pubmed
Elvin, Synthesis and properties of crosslinked recombinant pro-resilin. 2005, Pubmed
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Fedders, The antimicrobial peptide Ci-MAM-A24 is highly active against multidrug-resistant and anaerobic bacteria pathogenic for humans. 2010, Pubmed
Fedoreyev, Antiviral and Antioxidant Properties of Echinochrome A. 2018, Pubmed , Echinobase
Ferrario, Marine-derived collagen biomaterials from echinoderm connective tissues. 2017, Pubmed , Echinobase
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Fidler, Collagen IV and basement membrane at the evolutionary dawn of metazoan tissues. 2017, Pubmed
Flaig, In Vivo Analysis of the Biocompatibility and Immune Response of Jellyfish Collagen Scaffolds and its Suitability for Bone Regeneration. 2020, Pubmed
Flammang, Echinoderm adhesive secretions: from experimental characterization to biotechnological applications. 2005, Pubmed , Echinobase
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Gauglitz, Combined gene and stem cell therapy for cutaneous wound healing. 2011, Pubmed
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Glaser, A renaissance in marine pharmacology: from preclinical curiosity to clinical reality. 2009, Pubmed
Goh, Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons from the Common Sea Urchin Tissue. 2017, Pubmed , Echinobase
Green, Marine Structural Biomaterials in Medical Biomimicry. 2015, Pubmed
Grkovic, National Cancer Institute (NCI) Program for Natural Products Discovery: Rapid Isolation and Identification of Biologically Active Natural Products from the NCI Prefractionated Library. 2020, Pubmed
Guillemin, Comparison of coral resorption and bone apposition with two natural corals of different porosities. 1989, Pubmed
Guillen, Marine natural products from zoantharians: bioactivity, biosynthesis, systematics, and ecological roles. 2020, Pubmed
Harvey, The re-emergence of natural products for drug discovery in the genomics era. 2015, Pubmed
Harvey, Natural products in drug discovery. 2008, Pubmed
Haug, Antibacterial activity in Strongylocentrotus droebachiensis (Echinoidea), Cucumaria frondosa (Holothuroidea), and Asterias rubens (Asteroidea). 2002, Pubmed , Echinobase
Hennebert, An integrated transcriptomic and proteomic analysis of sea star epidermal secretions identifies proteins involved in defense and adhesion. 2015, Pubmed , Echinobase
Hennebert, Characterisation of the carbohydrate fraction of the temporary adhesive secreted by the tube feet of the sea star Asterias rubens. 2011, Pubmed , Echinobase
Hennebert, Sea star tenacity mediated by a protein that fragments, then aggregates. 2014, Pubmed , Echinobase
Hickey, Cellulose Biomaterials for Tissue Engineering. 2019, Pubmed
Higashi, Functional chondroitin sulfate from Enteroctopus dofleini containing a 3-O-sulfo glucuronic acid residue. 2015, Pubmed , Echinobase
Hossain, Northern Sea Cucumber (Cucumaria frondosa): A Potential Candidate for Functional Food, Nutraceutical, and Pharmaceutical Sector. 2020, Pubmed , Echinobase
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Hu, Combined SEP and anti-PD-L1 antibody produces a synergistic antitumor effect in B16-F10 melanoma-bearing mice. 2018, Pubmed , Echinobase
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Ivanchina, Steroid glycosides from marine organisms. 2011, Pubmed
Jang, Halocidin: a new antimicrobial peptide from hemocytes of the solitary tunicate, Halocynthia aurantium. 2002, Pubmed
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Jeon, Natural healing-inspired collagen-targeting surgical protein glue for accelerated scarless skin regeneration. 2017, Pubmed
Jeong, Echinochrome A protects mitochondrial function in cardiomyocytes against cardiotoxic drugs. 2014, Pubmed , Echinobase
Jeong, Echinochrome a increases mitochondrial mass and function by modulating mitochondrial biogenesis regulatory genes. 2014, Pubmed , Echinobase
Johnson, Open-access metabolomics databases for natural product research: present capabilities and future potential. 2015, Pubmed
Jorfi, Progress towards biocompatible intracortical microelectrodes for neural interfacing applications. 2015, Pubmed
Jouiaei, Ancient Venom Systems: A Review on Cnidaria Toxins. 2015, Pubmed
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Kariya, Structure of fucose branches in the glycosaminoglycan from the body wall of the sea cucumber Stichopus japonicus. 1997, Pubmed , Echinobase
Ke, The anti-lung cancer activity of SEP is mediated by the activation and cytotoxicity of NK cells via TLR2/4 in vivo. 2014, Pubmed , Echinobase
Ke, SEP enhanced the antitumor activity of 5-fluorouracil by up-regulating NKG2D/MICA and reversed immune suppression via inhibiting ROS and caspase-3 in mice. 2016, Pubmed , Echinobase
Khrunyk, Progress in Modern Marine Biomaterials Research. 2020, Pubmed
Kim, Echinochrome A regulates phosphorylation of phospholamban Ser16 and Thr17 suppressing cardiac SERCA2A Ca²⁺ reuptake. 2015, Pubmed , Echinobase
Kim, A Novel Atypical PKC-Iota Inhibitor, Echinochrome A, Enhances Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells. 2018, Pubmed , Echinobase
Kim, Echinochrome A Attenuates Cerebral Ischemic Injury through Regulation of Cell Survival after Middle Cerebral Artery Occlusion in Rat. 2019, Pubmed , Echinobase
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Komori, Toxins from the starfish Acanthaster planci and Asterina pectinifera. 1997, Pubmed , Echinobase
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Kovalchuk, Naturally Drug-Loaded Chitin: Isolation and Applications. 2019, Pubmed
Kunze, Brominated skeletal components of the marine demosponges, Aplysina cavernicola and Ianthella basta: analytical and biochemical investigations. 2013, Pubmed
Langasco, Natural collagenic skeleton of marine sponges in pharmaceutics: Innovative biomaterial for topical drug delivery. 2017, Pubmed
Lawrence, Bioactivity as an options value of sea cucumbers in the Egyptian Red Sea. 2010, Pubmed , Echinobase
Le, Ecteinascidins. A review of the chemistry, biology and clinical utility of potent tetrahydroisoquinoline antitumor antibiotics. 2015, Pubmed
Le Tourneau, Aplidine: a paradigm of how to handle the activity and toxicity of a novel marine anticancer poison. 2007, Pubmed
Leal, Trends in the discovery of new marine natural products from invertebrates over the last two decades--where and what are we bioprospecting? 2012, Pubmed , Echinobase
Lebedev, Echinochrome, a naturally occurring iron chelator and free radical scavenger in artificial and natural membrane systems. 2005, Pubmed
Lebedev, Iron chelators and free radical scavengers in naturally occurring polyhydroxylated 1,4-naphthoquinones. 2008, Pubmed
Lebedev, Antioxidant properties, autooxidation, and mutagenic activity of echinochrome a compared with its etherified derivative. 2001, Pubmed
Lee, Mussel-Inspired Adhesives and Coatings. 2011, Pubmed
Lee, Clavaspirin, an antibacterial and haemolytic peptide from Styela clava. 2001, Pubmed
Lee, Styelins, broad-spectrum antimicrobial peptides from the solitary tunicate, Styela clava. 1997, Pubmed
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Lin, A bacterial source for mollusk pyrone polyketides. 2013, Pubmed
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Macha, Marine Skeletons: Towards Hard Tissue Repair and Regeneration. 2018, Pubmed
Machado, Omics-based natural product discovery and the lexicon of genome mining. 2017, Pubmed
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Mohamed, Mechanisms of echinochrome potency in modulating diabetic complications in liver. 2016, Pubmed , Echinobase
Mohamed, The Possible Hypoglycemic Mechanisms of Echinochrome. 2018, Pubmed , Echinobase
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Naruse, Acrosome reaction-related steroidal saponin, Co-ARIS, from the starfish induces structural changes in microdomains. 2010, Pubmed , Echinobase
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Neto, Synthetic and Marine-Derived Porous Scaffolds for Bone Tissue Engineering. 2018, Pubmed
Newman, Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. 2020, Pubmed
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Park, Echinochrome A Promotes Ex Vivo Expansion of Peripheral Blood-Derived CD34+ Cells, Potentially through Downregulation of ROS Production and Activation of the Src-Lyn-p110δ Pathway. 2019, Pubmed
Park, Therapeutic Cell Protective Role of Histochrome under Oxidative Stress in Human Cardiac Progenitor Cells. 2019, Pubmed , Echinobase
Park, Therapeutic effects of a liquid bandage prepared with cellulose powders from Styela clava tunics and Broussonetia kazinoki bark: Healing of surgical wounds on the skin of Sprague Dawley rats. 2019, Pubmed
Paul, Chemical Ecology of Marine Sponges: New Opportunities through "-Omics". 2019, Pubmed
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Pavão, Ascidian (Chordata-Tunicata) glycosaminoglycans: extraction, purification, biochemical, and spectroscopic analysis. 2015, Pubmed
Pereira, Have marine natural product drug discovery efforts been productive and how can we improve their efficiency? 2019, Pubmed
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Pomin, Structure, biology, evolution, and medical importance of sulfated fucans and galactans. 2008, Pubmed , Echinobase
Pomin, Fucanomics and galactanomics: marine distribution, medicinal impact, conceptions, and challenges. 2012, Pubmed
Pomin, Review: an overview about the structure-function relationship of marine sulfated homopolysaccharides with regular chemical structures. 2009, Pubmed , Echinobase
Pomin, Holothurian fucosylated chondroitin sulfate. 2014, Pubmed , Echinobase
Pomin, Galactosaminoglycans: Medical Applications and Drawbacks. 2019, Pubmed , Echinobase
Potts, Developments in marine invertebrate primary culture reveal novel cell morphologies in the model bivalve Crassostrea gigas. 2020, Pubmed
Pozzolini, Production, Characterization and Biocompatibility Evaluation of Collagen Membranes Derived from Marine Sponge Chondrosia reniformis Nardo, 1847. 2018, Pubmed
Prajatelistia, Tunicate-Inspired Gallic Acid/Metal Ion Complex for Instant and Efficient Treatment of Dentin Hypersensitivity. 2016, Pubmed
Pénez, Antifouling properties of simple indole and purine alkaloids from the Mediterranean gorgonian Paramuricea clavata. 2011, Pubmed
Pérez-Matos, Bacterial diversity associated with the Caribbean tunicate Ecteinascidia turbinata. 2007, Pubmed
Qi, Steroids from the South China Sea gorgonian Subergorgia suberosa. 2010, Pubmed
Qi, Antifouling Compounds from Marine Invertebrates. 2017, Pubmed
Ramesh, Marine Natural Products from Tunicates and Their Associated Microbes. 2021, Pubmed
Rath, Meta-omic characterization of the marine invertebrate microbial consortium that produces the chemotherapeutic natural product ET-743. 2011, Pubmed
Rinehart, Didemnins: antiviral and antitumor depsipeptides from a caribbean tunicate. 1981, Pubmed
Robinson, Conotoxin gene superfamilies. 2014, Pubmed
Rojko, Pore formation by actinoporins, cytolysins from sea anemones. 2016, Pubmed
Sagar, Antiviral lead compounds from marine sponges. 2010, Pubmed
Sakai, Structure--activity relationships of the didemnins. 1996, Pubmed
Sanandiya, Tunichrome-inspired pyrogallol functionalized chitosan for tissue adhesion and hemostasis. 2019, Pubmed
Sayed, Echinochrome pigment as novel therapeutic agent against experimentally - induced gastric ulcer in rats. 2018, Pubmed , Echinobase
Scherlach, Mining and unearthing hidden biosynthetic potential. 2021, Pubmed
Schillaci, Paracentrin 1, a synthetic antimicrobial peptide from the sea-urchin Paracentrotus lividus, interferes with staphylococcal and Pseudomonas aeruginosa biofilm formation. 2014, Pubmed , Echinobase
Schofield, Identification and analysis of the bacterial endosymbiont specialized for production of the chemotherapeutic natural product ET-743. 2015, Pubmed
Schröder, Silicate modulates the cross-talk between osteoblasts (SaOS-2) and osteoclasts (RAW 264.7 cells): inhibition of osteoclast growth and differentiation. 2012, Pubmed
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Schöffski, Clinical impact of trabectedin (ecteinascidin-743) in advanced/metastatic soft tissue sarcoma. 2008, Pubmed
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