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The green macroalga Ulva rigida represents a promising feedstock for biorefinary due to its fast growth and cosmopolitan distribution. The main component of the cell walls of U. rigida is a sulfated glucuronorhamnan polysaccharide known as ulvan. Herein it was found that due to the high (hydrogen)sulfate group content of ulvan, hydrothermal autohydrolysis at 130 °C renders a high percentage of rhamnose (78–79 % recovery from the initial content in the raw material), a rare sugar of high added value. In addition, acid catalysis by a triflate-based graphene oxide under oxygen-free conditions at 180 °C affords moderate amounts of tartaric acid (24–26 %). The same triflate-based graphene oxide catalyst under oxygen pressure yields remarkably high percentages of succinic acid (65 %). The catalyst preserves its activity for at least five consecutive reuses., Financial support by the Spanish Ministry of Economy and Competitiveness (Severo Ochoa SEV2016-0683, RTI2018-890237-CO2-R1) and Generalitat Valenciana (Prometeo 2017−083) is gratefully acknowledged. Vasile I. Parvulescu kindly acknowledges UEFISCDI for financial support (project PN-III-P4-ID-PCE-2016-0146, Nr. 121/2017).

Construction of extracellular matrix-mimetic nanofilms has considerable potential in biomedical and nanomedicinal fields. In this work, we fabricated neurocompatible layer-by-layer (LbL) films based on ulvan (ULV), a highly sulfated polysaccharide having compositional similarity to glycosaminoglycans that play important functional roles in the brain. ULV was durably assembled as a film with chitosan, another marine-derived polysaccharide, and the film enabled the stable adhesion of primary hippocampal neurons with high viability, comparable to the conventional poly-d-lysine surface. Notably, the ULV-based LbL films accelerated neurite outgrowth and selectively suppressed the adhesion of astrocytes, highlighting its potential as an advanced platform for neural implants and devices.

Nowadays, biofouling is responsible for enormous economic losses in the maritime sector, and its treatment with conventional antifouling paints is causing significant problems to the environment. Biomimetism and green chemistry approaches are very promising research strategies for the discovery of new antifouling compounds. This study focused on the red alga Sphaerococcus coronopifolius, which is known as a producer of bioactive secondary metabolites. Fifteen compounds, including bromosphaerol (1), were tested against key marine biofoulers (five marine bacteria and three microalgae) and two enzymes associated with the adhesion process in macroalgae and invertebrates. Each metabolite presented antifouling activity against at least one organism/enzyme. This investigation also revealed that two compounds, sphaerococcinol A (4) and 14R-hydroxy-13,14-dihydro-sphaerococcinol A (5), were the most potent compounds without toxicity towards oyster larvae used as non-target organisms. These compounds are of high potential as they are active towards key biofoulers and could be produced by a cultivable alga, a fact that is important from the green chemistry point of view.

Biomass is defined as organic matter from living organisms represented in all kingdoms. It is recognized to be an excellent source of proteins, polysaccharides and lipids and, as such, embodies a tailored feedstock for new products and processes to apply in green industries. The industrial processes focused on the valorization of terrestrial biomass are well established, but marine sources still represent an untapped resource. Oceans and seas occupy over 70% of the Earth’s surface and are used intensively in worldwide economies through the fishery industry, as logistical routes, for mining ores and exploitation of fossil fuels, among others. All these activities produce waste. The other source of unused biomass derives from the beach wrack or washed-ashore organic material, especially in highly eutrophicated marine ecosystems. The development of high-added-value products from these side streams has been given priority in recent years due to the detection of a broad range of biopolymers, multiple nutrients and functional compounds that could find applications for human consumption or use in livestock/pet food, pharmaceutical and other industries. This review comprises a broad thematic approach in marine waste valorization, addressing the main achievements in marine biotechnology for advancing the circular economy, ranging from bioremediation applications for pollution treatment to energy and valorization for biomedical applications. It also includes a broad overview of the valorization of side streams in three selected case study areas: Norway, Scotland, and the Baltic Sea., This publication is based upon work from COST Action CA18238 (Ocean4Biotech), supported by COST (European Cooperation in Science and Technology). AR and KK: this research was funded by the Slovenian Research Agency (research core funding P1-0245 and P1-0237). AR: this publication has been produced with financial assistance of the Interreg MED Programme, co-financed by the European Regional Development Fund (Project No. 8MED20_4.1_SP_001, internal ref. 8MED20_4.1_SP_001) – B-Blue project. SG, CT, and JO: this work is financed by national funds from FCT – Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy – i4HB. JaB and WH: the preparation of the manuscript was supported by the Project CONTRA (Conversion of a Nuisance to a Resource and Asset #R090, 2018–2021) of the INTERREG Baltic Sea Region Program, and Polish Ministry of Science and Higher Education from the 2019–2021 science funding allocated for the implementation of international co-financed project W24/INTERREG BSR/2019. Research of Maris Klavins, VB, and LA was supported by ERDF project 1.1.1.1/16/A/050 “Variable fuel gasification for municipal solid waste recovery.” MC acknowledges the funding from CEEC program supported by FCT/MCTES (CEECIND/02968/2017) and Strategic Funding UIDB/04423/2020 and UIDP/04423/2020 supported by national funds provided by FCT and ERDF. AD acknowledges financial support provided by European Union’s Horizon 2020 research and innovation program under the grant agreement No 857287 and Latvian Council of Science research project No. lzp-2020/1-0054. MKa: the Interreg LAT_LIT Programme, co-financed by the European Regional Development Fund (LLI-525 ESMIC). LB acknowledges the funding from Erasmus + Project No. ECOBIAS 609967-EPP-1-2019-1-RS-EPPKA2-CBHE-JP; GA.2019-1991/001-001. Development of master curricula in ecological monitoring and aquatic bioassessment for Western Balkans HEIs/ECOBIAS. IS and KP acknowledge financial support provided by the projects CZ.02.1.01/0.0/0.0/17_048/0007323 and CZ.02.1.01/0.0/0.0/16_019/0000754 (Ministry of Education, Youth and Sports of the Czech Republic). ZV-G acknowledges support within the project No.1.1.1.2/VIAA/1/16/029 (Formula of peat-free soil conditioner with controlled-release fertilizing effect applicable for soil remediation and quality improvement of agricultural production). IZ: the projects SLTKT20427, KIK 17431 and SARASWATI 2.0. JuB: the project No.1.1.1.2/VIAA/3/19/531 (Innovative technologies for stabilization of landfills – diminishing of environmental impact and resources potential in frames of circular economy). The work conducted by CR, LA-H, and MA was fully financed by Møreforsking AS.

International audience; Magnetic Fe@Y composites (carbon coated magnetic iron nanoparticles incorporated in Y zeolite) with 5-8 wt% Fe were synthesized and characterized. Overall acidity of the samples ranges between 2.0 and 2.47 mmol/g and is given mostly by Lewis acid sites. The obtained materials were proven to catalyze the hydrolysis of Ulvan polysaccharide with high conversions. The distribution of the reaction products depends on the reaction conditions and the concentration of Ulvan. The catalytic properties-catalytic performances correlations clearly show the acid zeolite Y is the active phase for Ulvan hydrolysis while the iron nanoparticles enable the catalyst separation in a magnetic field. Under oxygen pressure, the selectivity was completely changed to succinic acid. All Fe@Y composites were recycled for 10 times with no change in the catalytic performances after a simple magnetic separation and washing with water.

Ulvan, a sulphated polysaccharide located in the cell walls of green algae that possesses unique structural properties albeit its repeating unit shares chemical affinity with glycosoaminoglycans, such as hyaluronan and chondroitin sulphate, has been increasingly studied over the years for applications in the pharmaceutical field. The increasing knowledge on ulvan's chemical properties and biological activities has triggered its utilization in hybrid materials, given its potential efficacy in biomedical applications. In the present review, the use of ulvan in the design of different biomaterials, including membranes, particles, hydrogels, 3D porous structures and nanofibers, is presented. The applications of these structures may vary from drug delivery to wound dressing or bone tissue engineering. In this context, general information regarding the structure and chemical variability, extraction processes, physicochemical properties, and biological activities of ulvan is reported.

Nisin is an attractive alternative to chemical preservatives in the food industry. It is a cationic peptide of 34 amino acid residues that exhibits antimicrobial activity against Gram-positive bacteria. To ensure nisin stability in food matrices, new nisin-loaded ulvan particles were developed by the complexation method. The interaction of nisin with ulvan was demonstrated by FT-IR spectroscopy and differential scanning calorimetry. The encapsulation efficiency was calculated at different pH values within the range of 4.0–7.0 and was found to have the highest value at pH 7.0. The size and surface charge of particles fabricated at different concentrations of nisin and pH values were determined. Nisin-loaded ulvan particles exhibited antimicrobial activity against Gram-positive bacteria comparable to that of free nisin. Therefore, the developed complexes have the potential for application as biopreservatives in the food industry. For the first time, the potential of ulvan as a carrier of antimicrobial agent nisin was demonstrated.

Hybrid composites of synthetic and natural polymers represent materials of choice for bone tissue engineering. Ulvan, a biologically active marine sulfated polysaccharide, is attracting great interest in the development of novel biomedical scaffolds due to recent reports on its osteoinductive properties. Herein, a series of hybrid polycaprolactone scaffolds containing ulvan either alone or in blends with κ-carrageenan and chondroitin sulfate was prepared and characterized. The impact of the preparation methodology and the polysaccharide composition on their morphology, as well as on their mechanical, thermal, water uptake and porosity properties was determined, while their osteoinductive potential was investigated through the evaluation of cell adhesion, viability, and osteogenic differentiation of seeded human adipose-derived mesenchymal stem cells. The results verified the osteoinductive ability of ulvan, showing that its incorporation into the polycaprolactone matrix efficiently promoted cell attachment and viability, thus confirming its potential in the development of biomedical scaffolds for bone tissue regeneration applications.

The antioxidant activity of the essential oils, as well as of the organic and hydroethanolic extracts, of the fresh needles of 54 pine taxa was evaluated using the peroxy-oxalate and luminol chemiluminescence assays. Among all evaluated essential oils, P. canariensis and P. attenuata displayed the highest levels of activity. P. contorta var. murrayana, followed by P. nigra var. caramanica, exhibited the highest antioxidant capacity among the organic extracts, while the most active hydroethanolic extract was that of P. nigra subsp. nigra. Based on the overall levels of activity, the latter taxon was selected for phytochemical analysis targeting the isolation of the bioactive constituents. As such, the organic extract of P. nigra subsp. nigra was subjected to chromatographic separations to yield 11 secondary metabolites (1&minus, 11) that were evaluated for their antioxidant activity. Nonetheless, the isolated compounds were found to be less active than the crude extract, thus suggesting the potential role of synergism.

Six new (1, 2, 6, 8, 13, and 20) and twenty previously isolated (3&ndash, 5, 7, 9&ndash, 12, 14&ndash, 19, and 21&ndash, 26) steroids featuring thirteen different carbocycle motifs were isolated from the organic extract of the soft coral Sinularia polydactyla collected from the Hurghada reef in the Red Sea. The structures and the relative configurations of the isolated natural products have been determined based on extensive analysis of their NMR and MS data. The cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activity of compounds 3&ndash, 7, 9&ndash, 20, and 22&ndash, 26, as well as their effect on androgen receptor-regulated transcription was evaluated in vitro in human tumor and non-cancerous cells. Steroids 22 and 23 showed significant cytotoxicity in the low micromolar range against the HeLa and MCF7 cancer cell lines, while migration of endothelial cells was inhibited by compounds 11, 12, 22, and 23 at 20 &micro, M. The results of the androgen receptor (AR) reporter assay showed that compound 11 exhibited the strongest inhibition of AR at 10 &micro, M, while it is noteworthy that steroids 10, 16, and 20 displayed increased inhibition of AR with decreasing concentrations. Additionally, compounds 11 and 23 showed neuroprotective activity on neuron-like SH-SY5Y cells.

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Ulvan, a bioactive natural sulfated polysaccharide, and gelatin, a collagen-derived biopolymer, have attracted interest for the preparation of biomaterials for different biomedical applications, due to their demonstrated compatibility for cell attachment and proliferation. Both ulvan and gelatin have exhibited osteoinductive potential, either alone or in combination with other materials. In the current work, a series of novel hybrid scaffolds based on crosslinked ulvan and gelatin was designed, prepared and characterized. Their mechanical performance, thermal stability, porosity, water-uptake and in vitro degradation ability were assessed, while their morphology was analyzed through scanning electron microscopy. The prepared hybrid ulvan/gelatin scaffolds were characterized by a highly porous and interconnected structure. Human adipose-derived mesenchymal stem cells (hADMSCs) were seeded in selected ulvan/gelatin hybrid scaffolds and their adhesion, survival, proliferation, and osteogenic differentiation efficiency was evaluated. Overall, it was found that the prepared hybrid sponge-like scaffolds could efficiently support mesenchymal stem cells&rsquo, adhesion and proliferation, suggesting that such scaffolds could have potential uses in bone tissue engineering.

Wound healing is a fundamental response to tissue injury and a number of natural products has been found to accelerate the healing process. Herein, we report the preparation of a series of different polarity (organic and aqueous) extracts of the marine isopod Ceratothoa oestroides and the in vivo evaluation of their wound healing activity after topical administration of ointments incorporating the various extracts on wounds inflicted on SKH-hr1 hairless mice. The most active extract was fractionated for enrichment in the bioactive constituents and the fractions were further evaluated for their wound healing activity, while their chemical profiles were analyzed. Wound healing was evaluated by clinical assessment, photo-documentation, histopathological analysis and measurement of biophysical skin parameters, such as transepidermal water loss (TEWL), hydration, elasticity, and skin thickness. The highest levels of activity were exerted by treatment of the wounds with a fraction rich in eicosapentaenoic acid (EPA), as well as myristic and palmitoleic acids. Topical application of the bioactive fraction on the wounds of mice resulted in complete wound closure with a skin of almost normal architecture without any inflammatory elements.

New systems for the controlled release of 1,7-dioxaspiro[5.5]undecane and (Z)-7-tetradecenal, the sex pheromones of olive fruit fly, Bactrocera oleae, and olive moth, Prays oleae, respectively, were developed utilizing electrospun micro/nanofiber matrices from inexpensive, biodegradable polymers, namely polycaprolactone, cellulose acetate and polyhydroxybutyrate. The incorporation of the pheromones in 5, 10 and 20% w/w in the electrospinning polymer blends allowed for the production of fiber mats with variable loading levels and release rates, ensuring however in all cases the release of pheromones for more than 16 weeks. Laboratory bioassays and field trapping tests showed that the fiber mats obtained from electrospinning of polyhydroxybutyrate solution containing 5% w/w 1,7-dioxaspiro[5.5]undecane and polycaprolactone solution containing 5% w/w (Z)-7-tetradecenal were almost twice as effective in attracting B. oleae and P. oleae males, respectively, in comparison to the positive controls used.

CXCR4 chemokine receptor represents an attractive pharmacological target due to its key role in cancer metastasis and inflammatory diseases. Starting from our previously-developed pharmacophoric model, we applied a combined computational and experimental approach that led to the identification of the hydantoin alkaloids parazoanthines, isolated from the Mediterranean Sea anemone Parazoanthus axinellae, as novel CXCR4 antagonists. Parazoanthine analogues were then synthesized to evaluate the contribution of functional groups to the overall activity. Within the panel of synthesized natural and non-natural parazoanthines, parazoanthine-B was identified as the most potent CXCR4 antagonist with an IC50 value of 9.3 nM, even though all the investigated compounds were able to antagonize in vitro the down-stream effects of CXC12, albeit with variable potency and efficacy. The results of our study strongly support this class of small molecules as potent CXCR4 antagonists in tumoral pathologies characterized by an overexpression of this receptor. Furthermore, their structure–activity relationships allowed the optimization of our pharmacophoric model, useful for large-scale in silico screening.

Dinoflagellates contain large amounts of omega-3 fatty acids, including the nutritionally important docosahexaenoic acid (DHA). However, their cultivation in suspensions is characterized by low growth rates. Twin-layer porous substrate photobioreactors (TL-PSBRs) have been shown to support growth of different microalgal species, including the robust dinoflagellate Symbiodinium voratum. In the present study, the potential of cultivating marine autotrophic dinoflagellate species in a TL-PSBR for DHA production was explored. Based on initial screening experiments, two Symbiodinium species with high biomass and DHA productivities were selected: the symbiotic Symbiodinium microadriaticum CCAC 2475 B and the free-living Symbiodinium voratum CCAC 3869 B. The effects of three different temperatures (17, 22 and 27 °C) and nitrogen regimes (nitrate, ammonium and nitrogen-free) on biomass growth, total lipid accumulation and fatty acid methyl esters (FAMEs) content, with emphasis on DHA, were evaluated. The two lower temperatures (17 and 22 °C) enhanced growth and total lipid accumulation of S. microadriaticum CCAC 2475 B and S. voratum CCAC 3869 B. Cultivation at 22 °C and nitrogen limitation led to a significant positive effect on DHA productivity. Symbiodinium. microadriaticum CCAC 2475 B reached a DHA productivity of 145.4 mg m−2 day−1 and DHA content in the dry biomass of 2% (w/w) after 4 days of nitrogen depletion. The results of the present study demonstrated that autotrophic dinoflagellates, when cultivated on a TL-PSBR, produce comparable amounts of lipids and fatty acids to other commercially used microalgal species including the valuable DHA.

Red algae of the genus Laurencia are known to biosynthesize and secrete an immense variety of secondary metabolites possessing a spectrum of biological activities against bacteria, invertebrates and mammalian cell lines. Following a rigorous cross-species screening process, herein we report the antifouling potential of 25 secondary metabolites derived from species of the genus Laurencia, as well as the thorough evaluation of the ecotoxicity of selected metabolites against non-target marine arthropods and vertebrate cell lines. A number of these secondary metabolites exhibited potent antifouling activity and performed well in all screening tests. Our results show that perforenol (9) possesses similar antifouling activity with that already described for bromosphaerol, which is used herein as a benchmark.

Thuwalallenes A&ndash, E (1&ndash, 3, 5 and 8) and thuwalenynes A&ndash, C (4, 6, 7), new C15 acetogenins featuring uncommon ring systems, along with cis-maneonene D (9), thyrsiferol (10) and 23-acetyl-thyrsiferol (11) were isolated from the organic extract of a population of the red alga Laurencia sp., collected at Rose Reef off the village of Thuwal in the Red Sea waters of the Kingdom of Saudi Arabia. The structure elucidation of the isolated natural products was based on extensive analysis of their spectroscopic data. Compounds 1&ndash, 6, 8, 10 and 11 were evaluated for their anti-inflammatory activity by quantifying nitric oxide (NO) release in response to TLR4 stimulation in macrophages. Besides compound 4 that did not exhibit any activity, all other tested metabolites inhibited NO production from activated macrophages. Among them, thyrsiferol (10) and 23-acetylthyrsiferol (11) displayed activity with IC50 values in the low nM scale without cytotoxicity.

In this work sixteen hydroxyl ammonium Protic Ionic Liquids derived from a proton transfer reaction between four different substituted amines and four different low molecular weight aliphatic and alicyclic carboxylic acids have been synthesized. The synthesized PILs were structurally characterized by NMR and FT-IR spectroscopy whereas two of their more important physicochemical properties namely viscosity and glass transition temperature (T g ) were evaluated. The effect of alkyl chain length and substitution on the anionic and cationic component of the PILs scaffold has been discussed for the studied properties. It seems that T g values are mainly affected by the carboxylate anion structure whereas viscosity is controlled mainly by the structural features of the cationic part of the PILs. In order to estimate their environmental impact and reinforce their “green” character, biodegradation studies, as well as toxicity evaluation experiments have also been conducted. The synthesized PILs can be confidently labelled as green considering that they are not toxic or present low toxicity to the nauplii of the brine shrimp A. salina whereas they show biodegradability levels between 41–64%, according to the manometric respirometric method which measures the biological oxygen demand (BOD 5 ) by microorganisms in order to degrade PILs via bio-oxidation in five days.

Twenty one sesquiterpenes were isolated from the organic extract of the Caribbean gorgonian Pseudopterogogia rigida. Among them, seven bisabolanes (1, 2, 9–11, 13 and 14), six cadinanes (15–20) and one sesquiterpene featuring a new tricyclic carbon skeleton (21) are new natural products, while two (6 and 7) are reported for the first time from a natural source. The structures of the new compounds were established by detailed analyses of their NMR and MS data. The isolated metabolites were evaluated for their inhibitory activity against CDC25 phosphatases, which represent possible targets related to cancer therapy. Compounds 4 and 18 were the most active with IC50 values of 1.88 and 3.44 μM, respectively, against the CDC25A isoform.

Six new (1, 2, and 4-7) and two previously reported (3 and 8) disulfides, along with 4-butyl-2,6-cycloheptadienone, γ-tocopherol, and δ-tocopherol, were isolated from an organic extract of the brown alga Dictyopteris membranacea, collected at Gerolimenas Bay, Greece. The structure elucidation of the isolated natural products was based on analysis of their spectroscopic data. Compounds 1, 3-6, and 8 were evaluated for their antibacterial and anti-inflammatory activities. None of the compounds displayed antibacterial activity against two resistant strains of Staphylococcus aureus and one strain of Escherichia coli. In contrast, metabolite 5 was able to cause strong inhibition of NO production with an IC50 value of 3.8 μM using an LPS stimulation assay.

Vagiallene (1), a rearranged C15 acetogenin with a molecular formula and a carbon skeleton unprecedented in natural products, was isolated as a trace constituent from the organic extract of the red alga Laurencia obtusa from Lefkada island. The planar structure and the relative configuration of 1 were established on the basis of extensive analysis of its spectroscopic data, while its absolute configuration was determined by comparison of its experimental and quantum-mechanically predicted electronic circular dichroism spectra.

From the organic extracts of five bacterial strains isolated from marine sediments collected in the East Mediterranean Sea, three new (15, 16, 31) and twenty-nine previously reported (1&ndash, 14, 17&ndash, 30, 32) metabolites bearing the 2,5-diketopiperazine skeleton were isolated. The structures of the chlorinated compounds 15, 16, and 31 were elucidated by extensive analysis of their spectroscopic data (NMR, MS, UV, IR). Compounds 15 and 16 were evaluated for their antifungal activity against Candida albicans and Aspergillus niger but were proven inactive. The relevant literature is supplemented with complete NMR assignments and revisions for the 29 previously reported compounds.

Covering: 1957 to 2017 Algae constitute a heterogeneous group of eukaryotic photosynthetic organisms, mainly found in the marine environment. Algae produce numerous metabolites that help them cope with the harsh conditions of the marine environment. Because of their structural diversity and uniqueness, these molecules have recently gained a lot of interest for the identification of medicinally useful agents, including those with potential anticancer activities. In the current review, which is not a catalogue-based one, we first highlight the major biological events that lead to various types of cancer, including metastatic ones, to chemoresistance, thus to any types of current anticancer treatment relating to the use of chemotherapeutics. We then review algal metabolites for which scientific literature reports anticancer activity. Lastly, we focus on algal metabolites with promising anticancer activity based on their ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. Thus, we highlight compounds that have, among others, one or more of the following characteristics: selectivity in reducing the proliferation of cancer cells over normal ones, potential for killing cancer cells through non-apoptotic signaling pathways, ability to circumvent MDR-related efflux pumps, and activity in vivo in relevant pre-clinical models.

Ulvan, a marine sulfated polysaccharide isolated from green algae, has been recently recognized as a natural biopolymer of biomedical interest. A series of lysozyme/ulvan complexes prepared under various charge ratios at physiological pH were studied. The resulting complexes were examined with light scattering techniques in order to characterize the size, the distribution and the ζ-potential of the nanocarriers, which were found to depend on the charge ratio employed. Increased complexation efficiency of lysozyme was observed for certain charge ratios, while ATR-FTIR data suggested that the protein structure after complexation was retained. Bacterial growth studies showed that lysozyme once complexed with ulvan not only retains its antibacterial activity against the Gram positive strain Staphylococcus aureus, but actually exhibits increased levels of activity. In this model study, the results highlight the potential of ulvan as a promising nanocarrier for positively charged bioactive molecules.

Objective: Aiming at the modified release of melatonin (MLT), electrospun-MLT loaded nanofibers, filled into hard gelatin and DRcapsTM capsules, were used as formulants. Methods: Cellulose acetate, polyvinylpyrrolidinone and hydroxypropylmethylcellusose (HPMC 2910) were used for the preparation of the fiber matrices through electrospinning. The in vitro modified release profile of MLT from the fabricated matrices in gastrointestinal-like fluids was studied. At pH 1.2, the formulations CA1, CA2, PV1, HP1, HP2 and the composite formulations CAPV1-CAPV5 in hard gelatin capsules exhibited fast MLT release. Results: In general, the same trend was observed at pH 6.8, with the exception of CAPV1 and CAPV2. These two composite formulations delivered 52.08% and 75.25% MLT, respectively at a slower pace (6 h) when encapsulated in DRcapsTM capsules. In all other cases, the release of MLT from DRcapsTM capsules filled with the MLT-loaded nanofibers reached 100% at 6h. Conclusion: These findings suggest that the MLT-loaded nanofibrous mats developed in this study exhibit a promising profile for treating sleep dysfunctions.

Extracts from three Salvia sp. (S. fruticosa, S. pomifera, and S. sclarea), native to the island of Crete, were fractionated using ethyl acetate and n-butanol and analyzed using liquid chromatography–diode array–mass spectrometry. The antioxidant potency of each fraction was assessed by the antiradical activity (AAR) and the hydroxyl free radical scavenging activity (SAHFR). The chromatographic analyses revealed a rich profile, composed of mainly of flavones, accompanied by a limited number of phenylpropanoids. The highest antioxidant activity was displayed by the n-butanol fraction of S. fruticosa, which also had the richest polyphenolic composition.

This work was performed under the frame of COST Action collaboration (COST Action CM1106). The generous contribution of AIRC (The Italian Association for Cancer Research) IG14536 to G.D. is gratefully acknowledged. A.H. acknowledges support from the János Bolyai fellowship of the Hungarian Academy of Sciences. Background: Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and to the development of drug resistance after a first platinum-based regimen. The presence of a specific population of “cancer stem cells” could be responsible of the relapse of the tumor, and of the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy. Method: We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them. Results and conclusion: Interestingly there were compounds active only on stem cells, only on differentiated cells and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients. Postprint

Food, besides providing nutrients to satisfy the metabolic requirements, through various bioactive constituents modulates a number of functions in the body, thus playing detrimental or beneficial roles in a number of diseases. Seaweeds are rich in polysaccharides, proteins, minerals, vitamins, secondary metabolites, and polyunsaturated fatty acids, with low caloric value. Macroalgae, producing a great variety of bioactive compounds that have exhibited a wide spectrum of activities ranging from the treatment of allergies, diabetes, hypertension, oxidative stress, inflammation, thrombosis, obesity, and lipidemia to serious degenerative disorders and cancer, have a high potential as a source of functional ingredients. In this chapter, an overview of the most important bioactive seaweed constituents with their potential use in functional foods is presented.

Eight new (1-8) structurally diverse diterpenes featuring five different carbocycles were isolated from the organic extracts of the red alga Sphaerococcus coronopifolius collected from the coastline of the Ionian Sea in Greece. The structures of the new natural products, seven of which were halogenated, and the relative configuration of their stereocenters were determined on the basis of comprehensive spectroscopic analyses, including NMR and HRMS data. Compounds 5 and 8 were found to possess in vitro antitumor activity against one murine and five human cancer cell lines with mean IC50 values 15 and 16 μM, respectively., SCOPUS: ar.j, info:eu-repo/semantics/published

Protic Ionic Liquids (PILs) are promising solvents with desirable physicochemical properties for a variety of applications. They are considered as greener alternatives to common organic solvents but in order to efficiently be characterized as green their environmental impact has to be assessed. In the present study, the design, synthesis and an initial potential hazard assessment of 11 naphthenic and benzoic acid based PILs is presented. PILs’ “greenness” is enhanced considering that they are non-toxic according to the aquatic toxicity evaluation and most of them show satisfactorily to extremely high biodegradability level. Moreover, two of their most important physicochemical properties, viscosity and glass transition temperature (Tg), were determined for selected ILs. The effect of the aromatic and alicyclic ring on the anions, the size and the presence of a hydroxyl substituent at anions and cations has been also discussed for the studied environmental and physicochemical properties.

Seven new ( 1 – 3 , 5 and 8 – 10 ) and three previously reported ( 4 , 6 and 7 ) 4α-methylated steroids were isolated from the organic extract of the gorgonian Litophyton mollis . The structures and the relative configurations of the isolated natural products were determined on the basis of extensive analyses of their NMR and MS data. Metabolites 1 and 5 – 8 exhibited cytotoxic activity against K562 human chronic myelogenous leukemia cells with IC 50 values below 10 μM, while at the same time displaying low toxicity against healthy PBMCs.

Synthetic biology approaches achieving the reconstruction of specific plant natural product biosynthetic pathways in dedicated microbial "chassis" have provided access to important industrial compounds (e.g., artemisinin, resveratrol, vanillin). However, the potential of such production systems to facilitate elucidation of plant biosynthetic pathways has been underexplored. Here we report on the application of a modular terpene production platform in the characterization of the biosynthetic pathway leading to the potent antioxidant carnosic acid and related diterpenes in Salvia pomifera and Rosmarinus officinalis.Four cytochrome P450 enzymes are identified (CYP76AH24, CYP71BE52, CYP76AK6, and CYP76AK8), the combined activities of which account for all of the oxidation events leading to the biosynthesis of the major diterpenes produced in these plants. This approach develops yeast as an efficient tool to harness the biotechnological potential of the numerous sequencing datasets that are increasingly becoming available through transcriptomic or genomic studies.

Background Several plant diterpenes have important biological properties. Among them, forskolin is a complex labdane-type diterpene whose biological activity stems from its ability to activate adenylyl cyclase and to elevate intracellular cAMP levels. As such, it is used in the control of blood pressure, in the protection from congestive heart failure, and in weight-loss supplements. Chemical synthesis of forskolin is challenging, and production of forskolin in engineered microbes could provide a sustainable source. To this end, we set out to establish a platform for the production of forskolin and related epoxy-labdanes in yeast. Results Since the forskolin biosynthetic pathway has only been partially elucidated, and enzymes involved in terpene biosynthesis frequently exhibit relaxed substrate specificity, we explored the possibility of reconstructing missing steps of this pathway employing surrogate enzymes. Using CYP76AH24, a Salvia pomifera cytochrome P450 responsible for the oxidation of C-12 and C-11 of the abietane skeleton en route to carnosic acid, we were able to produce the forskolin precursor 11β-hydroxy-manoyl oxide in yeast. To improve 11β-hydroxy-manoyl oxide production, we undertook a chassis engineering effort involving the combination of three heterozygous yeast gene deletions (mct1/MCT1, whi2/WHI2, gdh1/GDH1) and obtained a 9.5-fold increase in 11β-hydroxy-manoyl oxide titers, reaching 21.2 mg L−1. Conclusions In this study, we identify a surrogate enzyme for the specific and efficient hydroxylation of manoyl oxide at position C-11β and establish a platform that will facilitate the synthesis of a broad range of tricyclic (8,13)-epoxy-labdanes in yeast. This platform forms a basis for the heterologous production of forskolin and will facilitate the elucidation of subsequent steps of forskolin biosynthesis. In addition, this study highlights the usefulness of using surrogate enzymes for the production of intermediates of complex biosynthetic pathways. The combination of heterozygous deletions and the improved yeast strain reported here will provide a useful tool for the production of numerous other isoprenoids. Electronic supplementary material The online version of this article (doi:10.1186/s12934-016-0440-8) contains supplementary material, which is available to authorized users.

Nature, the most prolific source of biological and chemical diversity, has provided mankind with treatments for health problems since ancient times and continues to be the most promising reservoir of bioactive chemicals for the development of modern drugs. In addition to the terrestrial organisms that still remain a promising source of new bioactive metabolites, the marine environment, covering approximately 70% of the Earth’s surface and containing a largely unexplored biodiversity, offers an enormous resource for the discovery of novel compounds. According to the MarinLit database, more than 27,000 metabolites from marine macro- and microorganisms have been isolated to date providing material and key structures for the development of new products in the pharmaceutical, food, cosmeceutical, chemical, and agrochemical sectors. Algae, which thrive in the euphotic zone, were among the first marine organisms that were investigated as sources of food, nutritional supplements, soil fertilizers, and bioactive metabolites.

Four new (1–4) and six previously reported (5–10) α-pyrone polyketides, along with benzoic acid, hydrocinnamic acid, and (E)-cinnamic acid, were isolated from the organic extract resulting from the cultivation of the algicolous strain Streptomyces ambofaciens BI0048, which in turn was isolated from the inner tissues of the red alga Laurencia glandulifera. The structure elucidation of the isolated natural products was based on extensive analysis of their spectroscopic data (NMR, MS, UV, IR). Compounds 1–10 were evaluated for their antibacterial and cytotoxic activities against two multidrug-resistant strains of Staphylococcus aureus and one strain of Escherichia coli, as well as two human cancer cell lines.

Dendritic-linear-dendritic (DLD) hybrids are highly functional materials combining the properties of linear and dendritic polymers. Attempts to electrospin DLD polymers composed of hyperbranched dendritic blocks of 2,2-bis(hydroxymethyl) propionic acid on a linear poly(ethylene glycol) core proved unsuccessful. Nevertheless, when these DLD hybrids were blended with an array of different biodegradable polymers as entanglement enhancers, nanofibrous nonwovens were successfully prepared by electrospinning. The pseudogeneration degree of the DLDs, the nature of the co-electrospun polymer and the solvent systems used for the preparation of the electrospinning solutions exerted a significant effect on the diameter and morphology of the electrospun fibers. It is worth-noting that aqueous solutions of the DLD polymers and only 1% (w/v) poly(ethylene oxide) resulted in the production of smoother and thinner nanofibers. Such dendritic nanofibrous scaffolds can be promising materials for biomedical applications due to their biocompatibility, biodegradability, multifunctionality, and advanced structural architecture. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 135, 45949.

Macroalgae are a significant source of extracellular organic material in the coastal areas of the Mediterranean, including organic ligands which serve as modulators of metal complexing capacity. This paper examines the release of copper-complexing ligands by 24 macroalgal species, including chlorophyta, rhodophyta, ochrophyta as well as Posidonia oceanica, common throughout the Mediterranean. Metabolites isolated from the algae Dictyota dichotoma and Pterocladiella capillacea were examined for the first time regarding their Cu-complexing properties. The concentration of ligands (LT) and the copper-binding strength (log Kapp) of exudates and metabolites were determined by electrochemical methods. All algal species released ligands giving LT concentrations ranging from 109 to 744 nM in unfiltered samples. An increase in the concentration of ligands up to 15 times in comparison to the blank was observed after 48 h of culturing macroalgae in artificial seawater. The binding strength (log Kapp) varied among species from 7.0 to 8.6, except for the metabolites for which it was lower (log Kapp = 6). Most of the ligands released were in the dissolved phase, with the contribution of particulate and/or colloidal organic matter (up to 46% of total ligands) appearing to be important only in specific macroalgal species.

International audience; The purification of the chloroform extract from the brown invasive macroalga Sargassum muticum, through a series of chromatographic separations, yielded 12 fractions that were tested against strains of bacteria, microalgae, and fungi involved in marine biofilm formation. The chemical composition of four (a, c, g, and k) out of the six fractions that exhibited anti-microfouling activity was investigated. Fraction a contained saturated and unsaturated linear hydrocarbons (C12-C27). Arachidonic acid was identified as the major metabolite in fraction c whereas fraction g contained mainly palmitic, linolenic, and palmitoleic acids. Fraction k was submitted to further purification yielding the fraction kAcaF1e that was composed of galactoglycerolipids, active against the growth of two of the four bacterial strains (Shewanella putrefaciens and Polaribacter irgensii) and all tested fungi. These promising results, in particular the isolation and the activity of galactoglycerolipids, attest the potential of the huge biomass of S. muticum as a source of new environmentally friendly antifouling compounds.