Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and found that DSFF could activate macrophages. However, more investigations are needed to further evaluate whether DSFF could promote hematopoiesis in the chemotherapy process. In this study, the protective effect of DSFF (1.8-7.2 mg/kg, i.p.) on cyclophosphamide-induced hematopoietic damage in mice and the underlying mechanisms were investigated. Our results show that DSFF could restore the numbers of white blood cells, neutrophils, and platelets in the peripheral blood, and could also retard bone marrow cell decrease in mice with cyclophosphamide-induced hematopoietic damage. UPLC/Q-Extraction Orbitrap/MS/MS-based lipidomics results reveal 16 potential lipid biomarkers in a serum that responded to hematopoietic damage in mice. Among them, PC (20:1/14:0) and SM (18:0/22:0) were the key lipid molecules through which DSFF exerted protective actions. In a validation experiment, DSFF (6.25-100 μg/mL) could also promote K562 cell proliferation and differentiation in vitro. The current findings indicated that DSFF could affect the blood cells and bone marrow cells in vivo and thus showed good potential and application value in alleviating the hematopoietic damage caused by cyclophosphamide.

The α7 nicotinic acetylcholine receptor (nAChR) is widely distributed in the central and peripheral nervous systems and is closely related to a variety of nervous system diseases and inflammatory responses. The α7 nAChR subtype plays a vital role in the cholinergic anti-inflammatory pathway. In vivo, ACh released from nerve endings stimulates α7 nAChR on macrophages to regulate the NF-κB and JAK2/STAT3 signaling pathways, thereby inhibiting the production and release of downstream proinflammatory cytokines and chemokines. Despite a considerable level of recent research on α7 nAChR-mediated immune responses, much is still unknown. In this study, we used an agonist (PNU282987) and antagonists (MLA and α-conotoxin [A10L]PnIA) of α7 nAChR as pharmacological tools to identify the molecular mechanism of the α7 nAChR-mediated cholinergic anti-inflammatory pathway in RAW264.7 mouse macrophages. The results of quantitative PCR, ELISAs, and transcriptome analysis were combined to clarify the function of α7 nAChR regulation in the inflammatory response. Our findings indicate that the agonist PNU282987 significantly reduced the expression of the IL-6 gene and protein in inflammatory macrophages to attenuate the inflammatory response, but the antagonists MLA and α-conotoxin [A10L]PnIA had the opposite effects. Neither the agonist nor antagonists of α7 nAChR changed the expression level of the α7 nAChR subunit gene; they only regulated receptor function. This study provides a reference and scientific basis for the discovery of novel α7 nAChR agonists and their anti-inflammatory applications in the future.

Harmful algal blooms pose a challenge regarding food safety due to their erratic nature and forming circumstances which are yet to be disclosed. The best strategy to protect human consumers is through legislation and monitoring strategies. Global warming and anthropological intervention aided the migration and establishment of emerging toxin producers into Europe's temperate waters, creating a new threat to human public health. The lack of information, standards, and reference materials delay effective solutions, being a matter of urgent resolution. In this work, the recent findings of the presence of emerging azaspiracids, spirolildes, pinnatoxins, gymnodimines, palitoxins, ciguatoxins, brevetoxins, and tetrodotoxins on European Coasts are addressed. The information concerning emerging toxins such as new matrices, locations, and toxicity assays is paramount to set the risk assessment guidelines, regulatory levels, and analytical methodology that would protect the consumers.

Low molecular weight fucoidan (LMWF) has been reported to have immunomodulation effects through the increase of the activation and function of macrophages. In this study, the regulating effect of LMWF from Undaria pinnatifida grown in New Zealand on dendritic cells (DCs) was investigated. We discovered that LMWF could stimulate DCs' maturation and migration, as well as CD4+ and CD8+ T cells' proliferation in vitro. We proved that this immune promoting activity is activated through TLR4 and its downstream MAPK and NF-κB signaling pathways. Further in vivo (mouse model) investigation showed that LMWF has a strong immunological boosting effect, such as facilitating the proliferation of immune cells and increasing the index of immune organs. These findings suggest that LMWF has a positive immunomodulatory effect and is a promising candidate to supplement cancer immunotherapy.

Five new alkaloids have been isolated from the lipophilic extract of the Antarctic tunicate Synoicum sp. Deep-sea specimens of Synoicum sp. were collected during a 2011 cruise of the R/V Nathanial B. Palmer to the southern Scotia Arc, Antarctica. Crude extracts from the invertebrates obtained during the cruise were screened in a zebrafish-based phenotypic assay. The Synoicum sp. extract induced embryonic dysmorphology characterized by axis truncation, leading to the isolation of aminopyrimidine substituted indolone (1-4) and indole (5-12) alkaloids. While the primary bioactivity tracked with previously reported meridianins A-G (5-11), further investigation resulted in the isolation and characterization of australindolones A-D (1-4) and the previously unreported meridianin H (12).

Marine phycotoxins are a multiplicity of bioactive compounds which are produced by microalgae and bioaccumulate in the marine food web. Phycotoxins affect the ecosystem, pose a threat to human health, and have important economic effects on aquaculture and tourism worldwide. However, human health and food safety have been the primary concerns when considering the impacts of phycotoxins. Phycotoxins toxicity information, often used to set regulatory limits for these toxins in shellfish, lacks traceability of toxicity values highlighting the need for predefined toxicological criteria. Toxicity data together with adequate detection methods for monitoring procedures are crucial to protect human health. However, despite technological advances, there are still methodological uncertainties and high demand for universal phycotoxin detectors. This review focuses on these topics, including uncertainties of climate change, providing an overview of the current information as well as future perspectives.

Six new β-resorcylic acid derivatives (1-5 and 7) were isolated from a halophyte-associated fungus, Colletotrichum gloeosporioides JS0419, together with four previously reported β-resorcylic acid lactones (RALs). The relative and absolute stereochemistry of 1 was completely established by a combination of spectroscopic data and chemical reactions. The structures of the isolated compounds were elucidated by analysis of HRMS and NMR data. Notably, compounds 1-3 had a β-resorcylic acid harboring a long unesterified aliphatic side chain, whereas the long aliphatic chains were esterified to form macrolactones in 4-9. Among the isolated compounds, monocillin I and radicicol showed potent antifungal activities against Cryptococcus neoformans, comparable to clinically available antifungal agents and radicicol showed weak antifungal activity against Candida albicans. These findings provide insight into the chemical diversity of fungal RAL-type compounds and their pharmacological potential.

Microalgae are competitive and commercial sources for health-benefit carotenoids. In this study, a Chromochloris zofingiensis mutant (Cz-pkg), which does not shut off its photosystem and stays green upon glucose treatment, was generated and characterized. Cz-pkg was developed by treating the algal cells with a chemical mutagen as N-methyl-N'-nitro-N-nitrosoguanidine and followed by a color-based colony screening approach. Cz-pkg was found to contain a dysfunctional cGMP-dependent protein kinase (PKG). By cultivated with CO2 aeration under mixotrophy, the mutant accumulated lutein up to 31.93 ± 1.91 mg L-1 with a productivity of 10.57 ± 0.73 mg L-1 day-1, which were about 2.5- and 8.5-fold of its mother strain. Besides, the lutein content of Cz-pkg could reach 7.73 ± 0.52 mg g-1 of dry weight, which is much higher than that of marigold flower, the most common commercial source of lutein. Transcriptomic analysis revealed that in the mutant Cz-pkg, most of the genes involved in the biosynthesis of lutein and chlorophylls were not down-regulated upon glucose addition, suggesting that PKG may regulate the metabolisms of photosynthetic pigments. This study demonstrated that Cz-pkg could serve as a promising strain for both lutein production and glucose sensing study.

Fucus vesiculosus is one of the most prominent brown algae in the shallow waters of the seas of the Arctic region (Barents (BS), White (WS), Norwegian (NS), and Irminger (IS)). The aim of this study was to determine the biochemical composition of F. vesiculosus from the Arctic at different reproductive phases, and to evaluate the antioxidant properties of F. vesiculosus extracts. The amounts of monosaccharides, phlorotannins, flavonoids, and ash and the mineral composition significantly varied in the algae. A strong correlation was established between monosaccharide, phlorotannin, and flavonoid accumulation and water salinity (Pearson's correlation coefficients r = -0.58, 0.83, and 0.44, respectively; p < 0.05). We noted a negative correlation between the antioxidant activity and the amount of the structural monosaccharides of fucoidan (r = -0.64). A positive correlation of phlorotannins and flavonoids with antioxidant power was confirmed for all samples. The ash accumulation was relatively lower in the sterile phase for the algae from the BS and WS. The correlation between the Metal Pollution Index (MPI) and the reproductive phases was medium with high fluctuation. Meanwhile, the MPI strongly correlated with the salinity and sampling site. The gradient of the MPI values across the sea was in the following ranking order: BS < WS < NS < IS. Taken together, and based on our data on the elemental contents of F. vesiculosus, we believe that this alga does not accumulate toxic doses of elements. Therefore, the Arctic F. vesiculosus could be safely used in food and drug development as a source of active biochemical compounds and as a source of dietary elements to cover the daily nutritional requirements of humans.

A rapid and sensitive method using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied for the analysis of the metabolic profile of acarviostatin-containing aminooligosaccharides derived from Streptomyces sp. HO1518. A total of ninety-eight aminooligosaccharides, including eighty potential new compounds, were detected mainly based on the characteristic fragment ions originating from quinovosidic bond cleavages in their molecules. Following an LC-MS-guided separation technique, seven new aminooligosaccharides (10-16) along with four known related compounds (17-20) were obtained directly from the crude extract of strain HO1518. Compounds 10-13 represent the first examples of aminooligosaccharides with a rare acarviostatin II02-type structure. In addition, all isolates displayed considerable inhibitory effects on three digestive enzymes, which revealed that the number of the pseudo-trisaccharide core(s), the feasible length of the oligosaccharides, and acyl side chain exerted a crucial influence on their bioactivities. These results demonstrated that the UPLC-QTOF-MS/MS-based metabolomics approach could be applied for the rapid identification of aminooligosaccharides and other similar structures in complex samples. Furthermore, this study highlights the potential of acylated aminooligosaccharides with conspicuous α-glucosidase and lipase inhibition for the future development of multi-target anti-diabetic drugs.

Pseudomonas aeruginosa, one of the most intractable Gram-negative bacteria, has become a public health threat due to its outer polysaccharide layer, efflux transporter system, and high level of biofilm formation, all of which contribute to multi-drug resistance. Even though it is a pathogen of the highest concern, the status of the antibiotic development pipeline is unsatisfactory. In this review, we summarize marine natural products (MNPs) isolated from marine plants, animals, and microorganisms which possess unique structures and promising antibiotic activities against P. aeruginosa. In the last decade, nearly 80 such MNPs, ranging from polyketides to alkaloids, peptides, and terpenoids, have been discovered. Representative compounds exhibited impressive in vitro anti-P. aeruginosa activities with MIC values in the single-digit nanomolar range and in vivo efficacy in infectious mouse models. For some of the compounds, the preliminary structure-activity-relationship (SAR) and anti-bacterial mechanisms of selected compounds were introduced. Compounds that can disrupt biofilm formation or membrane integrity displayed potent inhibition of multi-resistant clinical P. aeruginosa isolates and could be considered as lead compounds for future development. Challenges on how to translate hits into useful candidates for clinical development are also proposed and discussed.

Oxidative stress has been implicated in the etiology of Parkinson's disease (PD). Molecules non-covalently binding to the Keap1-Nrf2 complex could be a promising therapeutic approach for PD. Herein, two novel prenylated indole alkaloids asperpenazine (1), and asperpendoline (2) with a scarce skeleton of pyrimido[1,6-a]indole were discovered from the co-cultivated fungi of Aspergillus ochraceus MCCC 3A00521 and Penicillium sp. HUBU 0120. Compound 2 exhibited potential neuroprotective activity on SH-SY5Y cells against oxidative stress. Molecular mechanism research demonstrated that 2 inhibited Keap1 expression, resulting in the translocation of Nrf2 from the cytoplasm to the nucleus, activating the downstream genes expression of HO-1 and NQO1, leading to the reduction in reactive oxygen species (ROS) and the augment of glutathione. Molecular docking and dynamic simulation analyses manifested that 2 interacted with Keap1 (PDB ID: 1X2R) via forming typical hydrogen and hydrophobic bonds with residues and presented less fluctuation of RMSD and RMSF during a natural physiological condition.

Species misidentification in the field of natural products is an acknowledged problem. These errors are especially widespread in sponge studies, albeit rarely assessed and documented. As a case study, we aim to revisit reports of isomalabaricane triterpenes, isolated from four demosponge genera: Jaspis, Geodia, Stelletta and Rhabdastrella. From a total of 44 articles (1981-2022), 27 unique vouchers were listed, 21 of which were accessed and re-examined here: 11 (52.4%) of these were misidentified. Overall, 65.9% of the studies published an incorrect species name: previously identified Jaspis and Stelletta species were all in fact Rhabdastrella globostellata. We conclude that isomalabaricane triterpenes were isolated from only two Rhabdastrella species and possibly one Geodia species. In addition to shedding a new light on the distribution of isomalabaricane triterpenes, this study is an opportunity to highlight the crucial importance of vouchers in natural product studies. Doing so, we discuss the impact of species misidentification and poor accessibility of vouchers in the field of sponge natural products. We advocate for stricter voucher guidelines in natural product journals and propose a common protocol of good practice, in the hope of reducing misidentifications in sponge studies, ensure reproducibility of studies, and facilitate follow-up work on the original material.

The glycoside hydrolase family 17 β-1,3-glucanase of Vibrio vulnificus (VvGH17) has two unknown regions in the N- and C-termini. Here, we characterized these domains by preparing mutant enzymes. VvGH17 demonstrated hydrolytic activity of β-(1→3)-glucan, mainly producing laminaribiose, but not of β-(1→3)/β-(1→4)-glucan. The C-terminal-truncated mutants (ΔC466 and ΔC441) showed decreased activity, approximately one-third of that of the WT, and ΔC415 lost almost all activity. An analysis using affinity gel containing laminarin or barley β-glucan revealed a shift in the mobility of the ΔC466, ΔC441, and ΔC415 mutants compared to the WT. Tryptophan residues showed a strong affinity for carbohydrates. Three of four point-mutations of the tryptophan in the C-terminus (W472A, W499A, and W542A) showed a reduction in binding ability to laminarin and barley β-glucan. The C-terminus was predicted to have a β-sandwich structure, and three tryptophan residues (Trp472, Trp499, and Trp542) constituted a putative substrate-binding cave. Linker and substrate-binding functions were assigned to the C-terminus. The N-terminal-truncated mutants also showed decreased activity. The WT formed a trimer, while the N-terminal truncations formed monomers, indicating that the N-terminus contributed to the multimeric form of VvGH17. The results of this study are useful for understanding the structure and the function of GH17 β-1,3-glucanases.

The genomic and carbohydrate metabolic features of Pseudoalteromonas agarivorans Hao 2018 (P. agarivorans Hao 2018) were investigated through pan-genomic and transcriptomic analyses, and key enzyme genes that may encode the process involved in its extracellular polysaccharide synthesis were screened. The pan-genome of the P. agarivorans strains consists of a core-genome containing 2331 genes, an accessory-genome containing 956 genes, and a unique-genome containing 1519 genes. Clusters of Orthologous Groups analyses showed that P. agarivorans harbors strain-specifically diverse metabolisms, probably representing high evolutionary genome changes. The Kyoto Encyclopedia of Genes and Genomes and reconstructed carbohydrate metabolic pathways displayed that P. agarivorans strains can utilize a variety of carbohydrates, such as d-glucose, d-fructose, and d-lactose. Analyses of differentially expressed genes showed that compared with the stationary phase (24 h), strain P. agarivorans Hao 2018 had upregulated expression of genes related to the synthesis of extracellular polysaccharides in the logarithmic growth phase (2 h), and that the expression of these genes affected extracellular polysaccharide transport, nucleotide sugar synthesis, and glycosyltransferase synthesis. This is the first investigation of the genomic and metabolic features of P. agarivorans through pan-genomic and transcriptomic analyses, and these intriguing discoveries provide the possibility to produce novel marine drug lead compounds with high biological activity.

Microalgae constitute a remarkable biological diversity but a limited number of them have been the object of study for their ability to produce exoplysaccharides (EPS). Among them, the red marine microalgae Porphyridium or Rhodella produce sulphated EPS, exhibiting some biological activities with potential interest in the pharmaceutical and cosmetic industries. EPS from Porphyridium and Rhodella being relatively similar in their composition, it has long been considered that all the red microalgae produced similar EPS and no attention was paid to other red microalgae. The objective of our work was then to explore the diversity of red microalgae for the production of EPS, focusing in this first step on the screening of the strains for their ability to produce EPS and preliminary structural characterization. The study was conducted with 11 microalgae strains belonging to the proteorhodophytina subphylum. All microalgae were able to produce EPS, released in the culture medium (strains belonging to Porphyridiophyceae and Rhodellophyceae classes) or remaining bound to the cells (strains from Stylonematophyceae class). The analysis of monosaccharides composition was found significantly different, with for instance high levels of glucuronic acids in the EPS from C. japonica and N. cyanea, but also strong differences in the sulphation degrees of polymers (between 1.2 and 28.7% eq. SO4).

In the last decades, it has been demonstrated that marine organisms are a substantial source of bioactive compounds with possible biotechnological applications. Marine sponges, in particular those belonging to the class of Demospongiae, have been considered among the most interesting invertebrates for their biotechnological potential. In this review, particular attention is devoted to natural compounds/extracts isolated from Demospongiae and their associated microorganisms with important biological activities for pharmacological applications such as antiviral, anticancer, antifouling, antimicrobial, antiplasmodial, antifungal and antioxidant. The data here presented show that this class of sponges is an exciting source of compounds, which are worth developing into new drugs, such as avarol, a hydroquinone isolated from the marine sponge Disidea avara, which is used as an antitumor, antimicrobial and antiviral drug.

Salmon byproducts (Salmo salar) generated by the food chain represent a source of long-chain polyunsaturated fatty acids (eicosapentaenoic acid (EPA): 20:5n-3; docosahexaenoic acid (DHA): 22:6n-3) and peptides that can be used as supplements in food for nutraceutical or health applications, such as in the prevention of certain pathologies (e.g., Alzheimer's and cardiovascular diseases). The extraction of polar lipids naturally rich in PUFAs by enzymatic processes without organic solvent (controlled by pH-Stat method), coupled with the production of 1 kDa salmon peptides by membrane filtration, allowed the formulation of nanocarriers. The physicochemical properties of the nanoliposomes (size ranging from 120 to 140 nm, PDI of 0.27, zeta potential between -32 and -46 mV and encapsulation efficiency) were measured, and the bioactivity of salmon hydrolysate peptides was assessed (antioxidant and antiradical activity: ABTS, ORAC, DPPH; iron metal chelation). Salmon peptides exhibited good angiotensin-conversion-enzyme (ACE) inhibition activity, with an IC50 value of 413.43 ± 13.12 µg/mL. Cytotoxicity, metabolic activity and proliferation experiments demonstrated the harmlessness of the nanostructures in these experimental conditions.

Alzheimer´s disease is a global neurodegenerative health concern. To prevent the disease, the simultaneous inhibition of acetylcholinesterase and oxidative stress is an efficient approach. In this study, the inhibition effect of all-trans astaxanthin mainly from marine organisms on acetylcholinesterase and oxidative stress was evaluated by a chemical-based method in vitro and cell assay model. The results show that all-trans astaxanthin was a reversible competitive inhibitor and exhibited a strong inhibition effect with half inhibitory concentration (IC50 value) of 8.64 μmol/L. Furthermore, all-trans astaxanthin inhibited oxidative stress through reducing malondialdehyde content and increasing the activity of superoxide dismutase as well as catalase. All-trans astaxanthin could induce the changes of the secondary structure to reduce acetylcholinesterase activity. Molecular-docking analysis reveals that all-trans astaxanthin prevented substrate from binding to acetylcholinesterase by occupying the space of the active pocket to cause the inhibition. Our finding suggests that all-trans astaxanthin might be a nutraceutical supplement for Alzheimer´s disease prevention.

As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin is considered to have neuroprotective activity via its excellent antioxidant properties. Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson's disease (PD), and is considered to be the cause of adverse reactions caused by the current PD commonly used treatment drug levodopa (l-DA). Supplementation with antioxidants early in PD can effectively prevent neurodegeneration and inhibit apoptosis in dopaminergic neurons. At present, the effect of fucoxanthin in improving the adverse effects triggered by long-term l-DA administration in PD patients is unclear. In the present study, we found that fucoxanthin can reduce cytotoxicity and suppress the high concentration of l-DA (200 μM)-mediated cell apoptosis in the 6-OHDA-induced PC12 cells through improving the reduction in mitochondrial membrane potential, suppressing ROS over-expression, and inhibiting active of ERK/JNK-c-Jun system and expression of caspase-3 protein. These results were demonstrated by PD mice with long-term administration of l-DA showing enhanced motor ability after intervention with fucoxanthin. Our data indicate that fucoxanthin may prove useful in the treatment of PD patients with long-term l-DA administration.

Marine sediment derived fungi are a very interesting source of biologically active compounds [...].

Inflammatory reactions are part of a complex biological response that plays a vital role in the appearance of various stimuli resulting from tissue and cell damage, the invasion of pathogenic bacteria, and the formation of the subsequent adaptive immune response. The production of many triggers and mediators of inflammation, which are inducers of pro-inflammatory factors, is controlled by numerous differentiation programs, through which inflammation is resolved and tissue homeostasis is restored. However, prolonged inflammatory responses or dysregulation of pro-inflammatory mechanisms can lead to chronic inflammation. Modern advances in biotechnology have made it possible to characterize the anti-inflammatory activity of phlorotannins, polyphenolic compounds from brown seaweed, and the mechanisms by which they modulate the inflammatory response. The purpose of this review is to analyze and summarize the results of numerous experimental in vitro and in vivo studies, illustrating the regulatory mechanisms of these compounds, which have a wide range of biological effects on the body. The results of these studies and the need for further research are discussed.

A polyoxygenated and halogenated labdane, spongianol (1); a polyoxygenated steroid, 3β,5α,9α-trihydroxy-24S-ethylcholest-7-en-6-one (2); a rare seven-membered lactone B ring, (22E,24S)-ergosta-7,22-dien-3β,5α-diol-6,5-olide (3); and an α,β-unsaturated fatty acid, (Z)-3-methyl-9-oxodec-2-enoic acid (4) as well as five known compounds, 10-hydroxykahukuene B (5), pacifenol (6), dysidamide (7), 7,7,7-trichloro-3-hydroxy-2,2,6-trimethyl-4-(4,4,4-trichloro-3-methyl-1-oxobu-tylamino)-heptanoic acid methyl ester (8), and the primary metabolite 2'-deoxynucleoside thymidine (9), have been isolated from the Red Sea sponge Spongia sp. The stereoisomer of 3 was discovered in Ganoderma resinaceum, and metabolites 5 and 6, isolated previously from red algae, were characterized unprecedentedly in the sponge. Compounds 7 and 8 have not been found before in the genus Spongia. Compounds 1-9 were also assayed for cytotoxicity as well as antibacterial and anti-inflammatory activities.

Cryptosporidium sp. are apicomplexan parasites that cause significant morbidity and possible mortality in humans and valuable livestock. There are no drugs on the market that are effective in the population most severely affected by this parasite. This study is the first high-throughput screen for potent anti-Cryptosporidium natural products sourced from a unique marine compound library. The Harbor Branch Oceanographic Institute at Florida Atlantic University has a collection of diverse marine organisms some of which have been subjected to medium pressure liquid chromatography to create an enriched fraction library. Numerous active compounds have been discovered from this library, but it has not been tested against Cryptosporidium parvum. A high-throughput in vitro growth inhibition assay was used to test 3764 fractions in the library, leading to the identification of 23 fractions that potently inhibited the growth of Cryptosporidium parvum. Bioassay guided fractionation of active fractions from a deep-sea sponge, Leiodermatium sp., resulted in the purification of leiodolide A, the major active compound in the organism. Leiodolide A displayed specific anti-Cryptosporidium activity at a half maximal effective concentration of 103.5 nM with selectivity indexes (SI) of 45.1, 11.9, 19.6 and 14.3 for human ileocecal colorectal adenocarcinoma cells (HCT-8), human hepatocellular carcinoma cells (Hep G2), human neuroblastoma cells (SH-SY5Y) and green monkey kidney cells (Vero), respectively. The unique structure of leiodolide A provides a valuable drug scaffold on which to develop new anti-Cryptosporidium compounds and supports the importance of screening natural product libraries for new chemical scaffolds.

Alexandriumpacificum is a typical toxic bloom-forming dinoflagellate, causing serious damage to aquatic ecosystems and human health. Many bacteria have been isolated, having algicidal effects on harmful algal species, while few algicidal bacteria have been found to be able to lyse A. pacificum. Herein, an algicidal bacterium, Shewanella Y1, with algicidal activity to the toxic dinoflagellate A. pacificum, was isolated from Jiaozhou Bay, China, and the physiological responses to oxidative stress in A. pacificum were further investigated to elucidate the mechanism involved in Shewanella Y1. Y1 exhibited a significant algicidal effect (86.64 ± 5.04% at 24 h) and algicidal activity in an indirect manner. The significant declines of the maximal photosynthetic efficiency (Fv/Fm), initial slope of the light limited region (alpha), and maximum relative photosynthetic electron transfer rate (rETRmax) indicated that the Y1 filtrate inhibited photosynthetic activities of A. pacificum. Impaired photosynthesis induced the overproduction of reactive oxygen species (ROS) and caused strong oxidative damage in A. pacificum, ultimately inducing cell death. These findings provide a better understanding of the biological basis of complex algicidal bacterium-harmful algae interactions, providing a potential source of bacterial agent to control harmful algal blooms.

Catharanthus roseus (L.) G. Don is a plant belonging to the genus Catharanthus of the Apocynaceae family. It contains more than one hundred alkaloids, of which some exhibit significant pharmacological activities. Chitooligosaccharides are the only basic aminooligosaccharides with positively charged cations in nature, which can regulate plant growth and antioxidant properties. In this study, the leaves of Catharanthus roseus were sprayed with chitooligosaccharides of different molecular weights (1 kDa, 2 kDa, 3 kDa) and different concentrations (0.01 μg/mL, 0.1 μg/mL, 1 μg/mL and 10 μg/mL). The fresh weights of its root, stem and leaf were all improved after chitooligosaccharides treatments. More importantly, the chitooligosaccharides elicitor strongly stimulated the accumulation of vindoline and catharanthine in the leaves, especially with the treatment of 0.1 μg/mL 3 kDa chitooligosaccharides, the contents of them were increased by 60.68% and 141.54%, respectively. Furthermore, as the defensive responses, antioxidant enzymes activities (catalase, glutathione reductase, ascorbate peroxidase, peroxidase and superoxide dismutase) were enhanced under chitooligosaccharides treatments. To further elucidate the underlying mechanism, qRT-PCR was used to investigate the genes expression levels of secologanin synthase (SLS), strictosidine synthase (STR), strictosidine glucosidase (SGD), tabersonine 16-hydroxylase (T16H), desacetoxyvindoline-4-hydroxylase (D4H), deacetylvindoline-4-O-acetyltransferase (DAT), peroxidase 1 (PRX1) and octadecanoid-responsive Catharanthus AP2-domain protein 3 (ORCA3). All the genes were significantly up-regulated after chitooligosaccharides treatments, and the transcription abundance of ORCA3, SLS, STR, DAT and PRX1 reached a maximal level with 0.1 μg/mL 3 kDa chitooligosaccharides treatment. All these results suggest that spraying Catharanthus roseus leaves with chitooligosaccharides, especially 0.1 μg/mL of 3 kDa chitooligosaccharides, may effectively improve the pharmaceutical value of Catharanthus roseus.

Fucoxanthin (FX) is a marine carotenoid that has proven to be a promising marine drug due to the multiple bioactivities it possesses. However, the instability and poor bioavailability of FX greatly limit its application in pharmaceuticals or functional foods. In this study, the creative construction of a solid lipid nanoparticle-microcapsule delivery system using mixed lipids of palm stearin and cholesterol wrapped with gelatin/Arabic gum to load lipophilic FX was fabricated, aiming to improve the stability and bioavailability of FX. The results showed that the encapsulated efficiency (EE) and drug loading capacity (LC) of optimized FX microcapsules (FX-MCs) obtained were as high as 96.24 ± 4.60% and 0.85 ± 0.04%, respectively, after single-factor experiments. The average particle size was 1154 ± 54 nm with negative Zeta potential (-20.71 ± 0.93 mV) as depicted with size-zeta potential spectrometer. The differential scanning calorimeter (DSC) and thermogravimetric analyzer (TG) results indicated that FX-MC has a higher Tg and slower weight loss than FX monomers (FX crystal) and blank MCs. Besides, The Fourier transform infrared spectrometer (FTIR) confirmed the good double encapsulation of FX into the solid lipid and composite coacervate. Moreover, the encapsulated FX showed higher storage stability, sustained release (55.02 ± 2.80% release in 8 h), and significantly improved bioavailability (712.33%) when compared to free FX. The research results can provide a principle theoretical basis for the development and application of FX in pharmaceuticals or functional foods.

Brevetoxins are a suite of marine neurotoxins that activate voltage-gated sodium channels (VGSCs) in cell membranes, with toxicity occurring from persistent activation of the channel at high doses. Lower doses, in contrast, have been shown to elicit neuroregeneration. Brevetoxins have thus been proposed as a novel treatment for patients after stroke, when neuron regrowth and repair is critical to recovery. However, findings from environmental exposures indicate that brevetoxins may cause inflammation, thus, there is concern for brevetoxins as a stroke therapy given the potential for neuroinflammation. In this study, we examined the inflammatory properties of several brevetoxin analogs, including those that do and do not bind strongly to VGSCs, as binding has classically indicated toxicity. We found that several analogs are toxic to monocytes, while others are not, and the degree of toxicity is not directly related to VGSC binding. Rather, results indicate that brevetoxins containing aldehyde groups were more likely to cause immunotoxicity, regardless of binding affinity to the VGSC. Our results demonstrate that different brevetoxin family members can elicit a spectrum of apoptosis and necrosis by multiple possible mechanisms of action in monocytes. As such, care should be taken in treating "brevetoxins" as a uniform group, particularly in stroke therapy research.

We investigated pigment and mycosporine-like amino acid (MAA) concentrations of phytoplankton and Northern krill (Thysanoessa sp.) in sub-Arctic Kongsfjorden. Chlorophyll a (Chl-a) concentrations in the surface and middle-layer water were 0.44 μg L-1 (±0.17 μg L-1) and 0.63 μg L-1 (±0.25 μg L-1), respectively. Alloxanthin (Allo, a marker of cryptophytes) was observed at all stations, and its mean values for surface and middle-layer water were 0.09 μg L-1 (±0.05 μg L-1) and 0.05 (±0.02 μg L-1), respectively. The mean MAA-to-Chl-a ratios at the surface (3.31 ± 2.58 μg (μg Chl-a)-1) were significantly higher than those in the middle-layer water (0.88 ± 0.49 μg (μg Chl-a)-1), suggesting that these compounds play an important role in reducing UV photodamage. In gut pigment levels of Northern krill, the most abundant accessory pigment was Allo (2.79 ± 0.33 μg g-1 dry weight; d.w.), as was the accumulation of Chl-a (8.29 ± 1.13 μg g-1 d.w.). The average concentration of MAAs was 1.87 mg g-1 d.w. (±0.88 mg g-1 d.w.) in krill eyes, which was higher than that in all other body parts (0.99 ± 0.41 mg g-1 d.w.), except for the gut. Thysanoessa sp. was found to contain five identified MAAs (shinorine, palythine, porphyra-334, mycosporine-glycine, and M-332) in the krill eye, whereas shinorine and porphyra-334 were only observed in the krill body, not the eyes and gut. These findings suggest that Northern krill accumulate MAAs of various compositions through the diet (mainly cryptophytes) and translocate them among their body parts as an adaptation for photoprotection and physiological demands.

Cancer stem cells (CSCs) drive aggressiveness and metastasis by utilizing stem cell-related signals. In this study, 5-O-(N-Boc-l-alanine)-renieramycin T (OBA-RT) was demonstrated to suppress CSC signals and induce apoptosis. OBA-RT exerted cytotoxic effects with a half-maximal inhibitory concentration of approximately 7 µM and mediated apoptosis as detected by annexin V/propidium iodide using flow cytometry and nuclear staining assays. Mechanistically, OBA-RT exerted dual roles, activating p53-dependent apoptosis and concomitantly suppressing CSC signals. A p53-dependent pathway was indicated by the induction of p53 and the depletion of anti-apoptotic Myeloid leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2) proteins. Cleaved poly (ADP-ribose) polymerase (Cleaved-PARP) was detected in OBA-RT-treated cells. Interestingly, OBA-RT exerted strong CSC-suppressing activity, reducing the ability to form tumor spheroids. In addition, OBA-RT could induce apoptosis in CSC-rich populations and tumor spheroid collapse. CSC markers, including prominin-1 (CD133), Octamer-binding transcription factor 4 (Oct4), and Nanog Homeobox (Nanog), were notably decreased after OBA-RT treatment. Upstream CSCs regulating active Akt and c-Myc were significantly decreased; indicating that Akt may be a potential target of action. Computational molecular modeling revealed a high-affinity interaction between OBA-RT and an Akt molecule. This study has revealed a novel CSC inhibitory effect of OBA-RT via Akt inhibition, which may improve cancer therapy.

Ciguatera Poisoning (CP) is caused by consumption of fish or invertebrates contaminated with ciguatoxins (CTXs). Presently CP is a public concern in some temperate regions, such as Macaronesia (North-Eastern Atlantic Ocean). Toxicity analysis was performed to characterize the fish species that can accumulate CTXs and improve understanding of the ciguatera risk in this area. For that, seventeen fish specimens comprising nine species were captured from coastal waters inMadeira and Selvagens Archipelagos. Toxicity was analysed by screening CTX-like toxicity with the neuroblastoma cell-based assay (neuro-2a CBA). Afterwards, the four most toxic samples were analysed with liquid chromatography-high resolution mass spectrometry (LC-HRMS). Thirteen fish specimens presented CTX-like toxicity in their liver, but only four of these in their muscle. The liver of one specimen of Muraena augusti presented the highest CTX-like toxicity (0.270 ± 0.121 µg of CTX1B equiv·kg-1). Moreover, CTX analogues were detected with LC-HRMS, for M. augusti and Gymnothorax unicolor. The presence of three CTX analogues was identified: C-CTX1, which had been previously described in the area; dihydro-CTX2, which is reported in the area for the first time; a putative new CTX m/z 1127.6023 ([M+NH4]+) named as putative C-CTX-1109, and gambieric acid A.

The marine pennate diatom Haslea ostrearia has long been known for its characteristic blue pigment marennine, which is responsible for the greening of invertebrate gills, a natural phenomenon of great importance for the oyster industry. For two centuries, this taxon was considered unique; however, the recent description of a new blue Haslea species revealed unsuspected biodiversity. Marennine-like pigments are natural blue dyes that display various biological activities-e.g., antibacterial, antioxidant and antiproliferative-with a great potential for applications in the food, feed, cosmetic and health industries. Regarding fundamental prospects, researchers use model organisms as standards to study cellular and physiological processes in other organisms, and there is a growing and crucial need for more, new and unconventional model organisms to better correspond to the diversity of the tree of life. The present work, thus, advocates for establishing H. ostrearia as a new model organism by presenting its pros and cons-i.e., the interesting aspects of this peculiar diatom (representative of benthic-epiphytic phytoplankton, with original behavior and chemodiversity, controlled sexual reproduction, fundamental and applied-oriented importance, reference genome, and transcriptome will soon be available); it will also present the difficulties encountered before this becomes a reality as it is for other diatom models (the genetics of the species in its infancy, the transformation feasibility to be explored, the routine methods needed to cryopreserve strains of interest).

Emodin, a hydroxyanthraquinone derivative, has been used as medicine for more than 2000 years due to its extensive pharmacological activities. Large-scale production of emodin has been achieved by optimizing the fermentation conditions of marine-derived Aspergillus flavus HN4-13 in a previous study. However, the fermentation broth contained complex unknown components, which adversely affected the study of emodin. Herein, the conditions for the enrichment of emodin from A. flavipes HN4-13 extract using XAD-16 resin were optimized, and a separation method with high efficiency, simple operation, a low cost, and a large preparative scale was established. The adsorption process of emodin on the XAD-16 resin conformed to pseudo-second-order kinetics and Langmuir models. The optimal conditions for the adsorption process were as follows: An emodin concentration, flow rate, and loading volume of 0.112 mg/mL, 2 BV/h, and 10 BV, respectively. For desorption, 50% ethanol was used to elute impurities and 80% ethanol was used to desorb emodin. After enrichment with XAD-16 resin, the emodin content increased from 1.16% to 11.48%, and the recovery rate was 75.53% after one-step treatment. These results demonstrate the efficiency of the simple adsorption-desorption strategy, using the XAD-16 resin for emodin enrichment.

Thraustochytrids have gained significant attention in recent years because of their considerable ecological and biotechnological importance. Yet, the influence of seasons and habitats on their culturable diversity and lipid profile remains poorly described. In this study, a total of 58 thraustochytrid strains were isolated from the coastal waters of Qingdao, China. These strains were phylogenetically close to five thraustochytrid genera, namely Botryochytrium, Oblongichytrium, Schizochytrium, Thraustochytrium, and Sicyoidochytrium. Most of the isolated strains were classified into the genera Thraustochytrium and Oblongichytrium. Further diversity analysis revealed that samples collected from nutrient-rich habitats and during summer/fall yielded significantly higher culturable diversity of thraustochytrids than those from low-nutrient habitats and winter/spring. Moreover, sampling habitats and seasons significantly impacted the fatty acid profiles of the strains. Particularly, the Oblongichytrium sp. OC931 strain produced a significant amount (153.99 mg/L) of eicosapentaenoic acid (EPA), accounting for 9.12% of the total fatty acids, which was significantly higher than that of the previously reported Aurantiochytrium strains. Overall, the results of this study fill the gap in our current understanding of the culturable diversity of thraustochytrids in the coastal waters and the impact of the sampling habitats and seasons on their capacity for lipid accumulation.

Antibiotic resistance and residues in aquaculture are a growing concern worldwide and consequently identifying favorable antibacterial compounds against aquatic pathogenic bacteria are gained more attention. Active compounds derived from marine microorganisms have shown great promise in this area. This review is aimed to make a comprehensive survey of anti-aquatic pathogenic bacterial compounds that were produced by marine microorganisms. A total of 79 compounds have been reported, covering literature from 1997 to 2021. The compounds are included in different structural classes such as polyketides, terpenoids, nitrogen compounds and others, and some of them present the potential to be developed into agents for the treatment of aquatic pathogenic bacteria.

Prostate cancer is a common cause of cancer death in men. In advanced stages of prostate cancer, androgen deprivation therapy (ADT) is initiated. Despite ADT, prostate cancers invariably progress to become androgen independent. A growing body of evidence implicates iron dysmetabolism in prostate cancer progression. A bioactive peptide-rich salmon protein hydrolysate (SPH) has previously been demonstrated to modulate iron homeostatic mechanisms. In the present study, the anticancer effect of SPH and bicalutamide co-treatment on LNCaP and PC3 prostate cancer cell proliferation was investigated. Our results found that SPH potentiates the anti-proliferative effect of bicalutamide in a dose-dependent manner for both cell lines. In the presence of 160 µg/mL SPH, co-treatment with 1.0 µM bicalutamide decreased LNCaP cells' relative colony survival from 25% (1.0 µM bicalutamide monotreatment) to 2% after culturing for 12 days. For PC3 cells, the relative colony survival diminished from 52% (10.0 µM bicalutamide) to 32% at an SPH concentration of 160 µg/mL. Gene expression profiling, employing quantitative real-time PCR, revealed that the inhibitory effects were related to significant FTH1 up-regulation with a concomitant TFRC down-regulation. In conclusion, our results provide in vitro evidence that SPH potentiates the growth inhibitory effect of bicalutamide on prostate cancer cells by modulating iron homeostasis mechanisms.

Thymic epithelial cells (TECs) account for the most abundant and dominant stromal component of the thymus, where T cells mature. Oxidative- or cytotoxic-stress associated injury in TECs, a significant and common problem in many clinical settings, may cause a compromised thymopoietic capacity of TECs, resulting in clinically significant immune deficiency disorders or impairment in the adaptive immune response in the body. The present study demonstrated that fish collagen peptides (FCP) increase cell viability, reduce intracellular levels of reactive oxygen species (ROS), and impede apoptosis by repressing the expression of Bax and Bad and the release of cytochrome c, and by upregulating the expression of Bcl-2 and Bcl-xL in cisplatin-treated TECs. These inhibitory effects of FCP on TEC damage occur via the suppression of ROS generation and MAPK (p38 MAPK, JNK, and ERK) activity. Taken together, our data suggest that FCP can be used as a promising protective agent against cytotoxic insults- or ROS-mediated TEC injury. Furthermore, our findings provide new insights into a therapeutic approach for the future application of FCP in the prevention and treatment of various types of oxidative- or cytotoxic stress-related cell injury in TECs as well as age-related or acute thymus involution.

Cyanobacteria, particularly thermophilic strains, represent an important potential source of EPSs, harboring structural complexity that predicts diverse and specific bioactive potential. The thermophilic cyanobacteria Gloeocapsa gelatinosa, isolated from a natural hot source in Ain Echfa (Tunisia), was cultivated in a cylindrical reactor, and the production of biomass and EPSs was investigated. Results revealed that the strain is amongst the most efficient EPSs producers (0.89 g L-1) and that EPSs production was not correlated with the growth phase. EPSs were sulfated heteropolysaccharides containing carbohydrates (70%) based on nine different monosaccharides, mainly mannose (22%), and with the presence of two uronic acids. EPSs were formed by two polymers moieties with a molecular weight of 598.3 ± 7.2 and 67.2 ± 4.4 kDa. They are thermostable in temperatures exceeding 100 °C and have an anionic nature (zeta potential of -40 ± 2 mV). Atomic force microscopy showed that EPSs formed multimodal lumps with 88 nm maximum height. EPSs presented high water holding capacity (70.29 ± 2.36%) and solubility index (97.43 ± 1.24%), and a strong bivalent metal sorption capacity especially for Cu2+ (91.20 ± 1.25%) and Fe2+ (75.51 ± 0.71%). The antioxidant activity of G. gelatinosa EPSs was investigated using four methods: the β-carotene-bleaching activity, DPPH assays, iron-reducing activity, and metal-chelating activity. EPS has shown high potential as free radicals' scavenger, with an IC50 on DPPH (0.2 g L-1) three-fold lower than ascorbic acid (0.6 g L -1) and as a metal chelating activity (IC50 = 0.4 g L-1) significantly lower than EDTA. The obtained results allow further exploration of the thermophilic G. gelatinosa for several biotechnological and industrial applications.

The vast ocean holds many unexplored organisms with unique adaptive features that enable them to thrive in their environment. The secretion of fluorescent proteins is one of them, with reports on the presence of such compounds in marine annelids being scarce. The intertidal Eulalia sp. is an example. The worm secretes copious amounts of mucus, that when purified and concentrated extracts, yield strong fluorescence under UV light. Emission has two main maxima, at 400 nm and at 500 nm, with the latter responsible for the blue-greenish fluorescence. Combining proteomics and transcriptomics techniques, we identified ubiquitin, peroxiredoxin, and 14-3-3 protein as key elements in the mucus. Fluorescence was found to be mainly modulated by redox status and pH, being consistently upheld in extracts prepared in Tris-HCl buffer with reducing agent at pH 7 and excited at 330 nm. One of the proteins associated with the fluorescent signal was localized in secretory cells in the pharynx. The results indicate that the secretion of fluorescent proteinaceous complexes can be an important defense against UV for this dweller. Additionally, the internalization of fluorescent complexes by ovarian cancer cells and modulation of fluorescence of redox status bears important considerations for biotechnological application of mucus components as markers.

Two new cytotoxic metabolites, halosmysins B and C, have been isolated from the fungus Halosphaeriaceae sp. OUPS-135D-4 separated from the marine alga Sargassum thunbergii. These chemical structures have been elucidated by 1D and 2D NMR, and HRFABMS spectral analyses. The new compounds had the same 14-membered macrodiolide skeleton as halosmysin A, which was isolated from this fungal strain previously. As the unique structural feature, a diketopiperazine derivative and a sugar are conjugated to the 14-membered ring of halosmysins B and C, respectively. The absolute stereostructures of them were elucidated by the chemical derivatization such as a hydrolysis, the comparison with the known compounds (6R,11R,12R,14R)-colletodiol and halosmysin A, and a HPLC analysis of sugar. In addition, their cytotoxicities were assessed using murine P388 leukemia, human HL-60 leukemia, and murine L1210 leukemia cell lines. Halosmysin B was shown to be potent against all of them, with IC50 values ranging from 8.2 ± 1.8 to 20.5 ± 3.6 μM, though these values were slightly higher than those of halosmysin A.

Fucoxanthin, a xanthophyll carotenoid abundant in brown algae, is reported to have several biological functions, such as antioxidant, anti-inflammatory, and anti-tumor activities, in mice. We investigated the effects and mechanisms of fucoxanthin in the mixture oleate/palmitate = 2/1(FFA)-induced nonalcoholic fatty liver disease (NAFLD) cell model in this study. The results showed that the content of superoxide dismutase in the FFA group was 9.8 ± 1.0 U/mgprot, while that in the fucoxanthin high-dose (H-Fx) group (2 μg/mL) increased to 22.9 ± 0.6 U/mgprot. The content of interleukin-1β in the FFA group was 89.3 ± 3.6 ng/mL, while that in the H-Fx group was reduced to 53.8 ± 2.8 ng/mL. The above results indicate that fucoxanthin could alleviate the FFA-induced oxidative stress and inflammatory levels in the liver cells. Oil red-O staining revealed visible protrusions and a significant decrease in the number of lipid droplets in the cytoplasm of cells in the fucoxanthin group. These findings on the mechanisms of action suggest that fucoxanthin can repair FFA-induced NAFLD via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and nuclear factor erythroid-2-related factor 2-mediated (Nrf2) signaling pathway, as well as by downregulating the expression of the Toll-like receptor 4-mediated (TLR4) signaling pathway. Fucoxanthin exhibited alleviating effects in the FFA-induced NAFLD model and could be explored as a potential anti-NAFLD substance.

An immunomodulatory polysaccharide (DAP4) was extracted, purified, and characterized from Durvillaea antarctica. The results of chemical and spectroscopic analyses demonstrated that the polysaccharide was a fucoidan, and was mainly composed of (1→3)-α-l-Fucp and (1→4)-α-l-Fucp residues with a small degree of branching at C-3 of (1→4)-α-l-Fucp residues. Sulfate groups were at C-4 of (1→3)-α-l-Fucp, C-2 of (1→4)-α-l-Fucp and minor C-6 of (1→4)-β-d-Galp. Small amounts of xylose and galactose exist in the forms of β-d-Xylp-(1→ and β-d-Gal-(1→. The immunomodulatory activity of DAP4 was measured on RAW 264.7 cells, the results proved that DAP4 exhibited excellent immunomodulatory activities, such as promoted the proliferation of spleen lymphocytes, increased NO production, as well as enhanced phagocytic of macrophages. Besides, DAP4 could also produce better enhancement on the vitality of NK cells. For the high immunomodulatory activity, DAP4 might be a potential source of immunomodulatory fucoidan with a novel structure.

Marine environment has been identified as a huge reservoir of novel biometabolites that are beneficial for medical treatments, as well as improving human health and well-being. Sponges have been highlighted as one of the most interesting phyla as new metabolites producers. Dactylospongia elegans Thiele (Thorectidae) is a wealth pool of various classes of sesquiterpenes, including hydroquinones, quinones, and tetronic acid derivatives. These metabolites possessed a wide array of potent bioactivities such as antitumor, cytotoxicity, antibacterial, and anti-inflammatory. In the current work, the reported metabolites from D. elegans have been reviewed, including their bioactivities, biosynthesis, and synthesis, as well as the structural-activity relationship studies. Reviewing the reported studies revealed that these metabolites could contribute to new drug discovery, however, further mechanistic and in vivo studies of these metabolites are needed.

Fucoxanthin is a brown-colored pigment from algae, with great potential as a bioactive molecule due to its numerous properties. This review aims to present current knowledge on this high added-value pigment. An accurate analysis of the biological function of fucoxanthin explains its wide photon absorption capacities in golden-brown algae. The specific chemical structure of this pigment also leads to many functional activities in human health. They are outlined in this work and are supported by the latest studies in the literature. The scientific and industrial interest in fucoxanthin is correlated with great improvements in the development of algae cultures and downstream processes. The best fucoxanthin producing algae and their associated culture parameters are described. The light intensity is a major influencing factor, as it has to enable both a high biomass growth and a high fucoxanthin content. This review also insists on the most eco-friendly and innovative extraction methods and their perspective within the next years. The use of bio-based solvents, aqueous two-phase systems and the centrifugal partition chromatography are the most promising processes. The analysis of the global market and multiple applications of fucoxanthin revealed that Asian companies are major actors in the market with macroalgae. In addition, fucoxanthin from microalgae are currently produced in Israel and France, and are mostly authorized in the USA.

Haematococcus pluvialis is a microalgae actively studied for the production of natural astaxanthin, which is a powerful antioxidant for human application. However, it is economically disadvantageous for commercialization owing to the low productivity of astaxanthin. This study reports an effective screening strategy using the negative phototaxis of the H. pluvialis to attain the mutants having high astaxanthin production. A polydimethylsiloxane (PDMS)-based microfluidic device irradiated with a specific light was developed to efficiently figure out the phototactic response of H. pluvialis. The partial photosynthesis deficient (PP) mutant (negative control) showed a 0.78-fold decreased cellular response to blue light compared to the wild type, demonstrating the positive relationship between the photosynthetic efficiency and the phototaxis. Based on this relationship, the Haematococcus mutants showing photosensitivity to blue light were selected from the 10,000 random mutant libraries. The M1 strain attained from the phototaxis-based screening showed 1.17-fold improved growth rate and 1.26-fold increases in astaxanthin production (55.12 ± 4.12 mg g-1) in the 100 L photo-bioreactor compared to the wild type. This study provides an effective selection tool for industrial application of the H. pluvialis with improved astaxanthin productivity.

Aquatic invertebrates are a major source of biomaterials and bioactive natural products that can find applications as pharmaceutics, nutraceutics, cosmetics, antibiotics, antifouling products and biomaterials. Symbiotic microorganisms are often the real producers of many secondary metabolites initially isolated from marine invertebrates; however, a certain number of them are actually synthesized by the macro-organisms. In this review, we analysed the literature of the years 2010-2019 on natural products (bioactive molecules and biomaterials) from the main phyla of marine invertebrates explored so far, including sponges, cnidarians, molluscs, echinoderms and ascidians, and present relevant examples of natural products of interest to public and private stakeholders. We also describe omics tools that have been more relevant in identifying and understanding mechanisms and processes underlying the biosynthesis of secondary metabolites in marine invertebrates. Since there is increasing attention on finding new solutions for a sustainable large-scale supply of bioactive compounds, we propose that a possible improvement in the biodiscovery pipeline might also come from the study and utilization of aquatic invertebrate stem cells.

Sea stars or starfish (class Asteroidea) and holothurians or sea cucumbers (class Holothuroidea), belonging to the phylum Echinodermata (echinoderms), are characterized by different sets of glycosidic metabolites: the steroid type in starfish and the triterpene type in holothurians. However, herein we report the isolation of eight new triterpene glycosides, pacificusosides D-K (1-3, 5-9) along with the known cucumarioside D (4), from the alcoholic extract of the Far Eastern starfish Solaster pacificus. The isolated new compounds are closely related to the metabolites of sea cucumbers, and their structures of 1-3 and 5-9 were determined by extensive NMR and ESIMS techniques. Compounds 2, 5, and 8 have a new type of tetrasaccharide chain with a terminal non-methylated monosaccharide unit. Compounds 3, 6, and 9 contain another new type of tetrasaccharide chain, having 6-O-SO3-Glc as one of the sugar units. The cytotoxic activity of 1-9 against non-cancerous mouse epidermal cells JB6 Cl41 and human melanoma cell lines SK-MEL-2, SK-MEL-28, and RPMI-7951 was determined by MTS assay. Compounds 1, 3, 4, 6, and 9 showed potent cytotoxicity against these cell lines, but the cancer selectivity (SI > 9) was observed only against the SK-MEL-2 cell line. Compounds 1, 3, 4, 6, and 9 at the non-toxic concentration of 0.1 μM significantly inhibited neoplastic cell transformation of JB6 Cl41 cells induced by chemical carcinogens (EGF, TPA) or ionizing radiation (X-rays and UVB). Moreover, compounds 1 and 4 at the non-toxic concentration of 0.1 µM possessed the highest inhibiting activity on colony formation among the investigated compounds and decreased the colonies number of SK-MEL-2 cells by 64% and 70%, respectively. Thus, triterpene glycosides 1 and 4 can be considered as prospective cancer-preventive and anticancer-compound leaders.

Three complex polyoxygenated diterpenoids possessing uncommon tetradecahydro-2,13:6,9-diepoxybenzo[10]annulene scaffold, namely ximaoornatins A-C (1-3), one new eunicellin-type diterpene, litophynin K (4), and a related known compound, litophynol B (5) were isolated from the South China Sea soft coral Sinularia ornata. The structures and absolute configurations of 1-4 were established by extensive spectroscopic analysis, X-ray diffraction analysis, and/or modified Mosher's method. A plausible biosynthetic relationship of 1 and its potential precursor 4 was proposed. In a bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages and PTP1B inhibitory effects.

The world is already facing the devastating effects of the SARS-CoV-2 pandemic. A disseminated mucormycosis epidemic emerged to worsen this situation, causing havoc, especially in India. This research aimed to perform a multitargeted docking study of marine-sponge-origin bioactive compounds against mucormycosis. Information on proven drug targets and marine sponge compounds was obtained via a literature search. A total of seven different targets were selected. Thirty-five compounds were chosen using the PASS online program. For homology modeling and molecular docking, FASTA sequences and 3D structures for protein targets were retrieved from NCBI and PDB databases. Autodock Vina in PyRx 0.8 was used for docking studies. Further, molecular dynamics simulations were performed using the IMODS server for top-ranked docked complexes. Moreover, the drug-like properties and toxicity analyses were performed using Lipinski parameters in Swiss-ADME, OSIRIS, ProTox-II, pkCSM, and StopTox servers. The results indicated that naamine D, latrunculin A and S, (+)-curcudiol, (+)-curcuphenol, aurantoside I, and hyrtimomine A had the highest binding affinity values of -8.8, -8.6, -9.8, -11.4, -8.0, -11.4, and -9.0 kcal/mol, respectively. In sum, all MNPs included in this study are good candidates against mucormycosis. (+)-curcudiol and (+)-curcuphenol are promising compounds due to their broad-spectrum target inhibition potential.

Aspergillus is well-known as the second-largest contributor of fungal natural products. Based on NMR guided isolation, three nitrogen-containing secondary metabolites, including two new compounds, variotin B (1) and coniosulfide E (2), together with a known compound, unguisin A (3), were isolated from the ethyl acetate (EtOAc) extract of the deep-sea fungus Aspergillus unguis IV17-109. The planar structures of 1 and 2 were elucidated by an extensive analysis of their spectroscopic data (HRESIMS, 1D and 2D NMR). The absolute configuration of 2 was determined by comparison of its optical rotation value with those of the synthesized analogs. Compound 2 is a rare, naturally occurring substance with an unusual cysteinol moiety. Furthermore, 1 showed moderate anti-inflammatory activity with an IC50 value of 20.0 µM. These results revealed that Aspergillus unguis could produce structurally diverse nitrogenous secondary metabolites, which can be used for further studies to find anti-inflammatory leads.

The beneficial effects of fish-derived lipid bioactives have come to prominence over the last few decades, especially for their utilization in fish oils, supplements, and nutraceuticals. Omega-3 (n-3) polyunsaturated fatty acids (PUFA), lipid vitamins, carotenoids, and polar lipid bioactives from fish have shown to possess a vast range of beneficial effects against a multitude of chronic disorders and especially against inflammation-and cardiovascular disorders (CVD). The observed cardio-protective effects and health benefits are believed to be attributed to the synergy of these fish-derived lipid bioactives. Within the present article the recent findings in the literature on the lipid content of the mainly consumed fish species, their bio-functionality, and cardio-protective benefits is thoroughly reviewed. Moreover, the recovery and valorization of such lipid bioactives from fish by-products and fishing by-catch, in order to reduce waste, while developing useful products containing cardio-protective lipids from the leftover materials of fisheries and aquaculture industries, are also of industrial and environmental interest. Emphasis is also given to the effects of heat treatments during fish processing on the structures and bio-functionality of these marine lipid bioactives, based on the paradigm of different cooking methodologies and thermal processing, while the compounds produced during such treatment(s) with detrimental changes in the fish lipid profile, which can reduce its cardio-protective efficacy, are also reviewed. Novel green extraction technologies and low temperature processing and cooking of fish and fishery by-products are needed to reduce these undesirable effects in a sustainable and environmentally friendly way.

Marine alkaloid fascaplysin and its derivatives are known to exhibit promising anticancer properties in vitro and in vivo. However, toxicity of these molecules to non-cancer cells was identified as a main limitation for their clinical use. Here, for the very first time, we synthesized a library of fascaplysin derivatives covering all possible substituent introduction sites, i.e., cycles A, C and E of the 12H-pyrido[1-2-a:3,4-b']diindole system. Their selectivity towards human prostate cancer versus non-cancer cells, as well as the effects on cellular metabolism, membrane integrity, cell cycle progression, apoptosis induction and their ability to intercalate into DNA were investigated. A pronounced selectivity for cancer cells was observed for the family of di- and trisubstituted halogen derivatives (modification of cycles A and E), while a modification of cycle C resulted in a stronger activity in therapy-resistant PC-3 cells. Among others, 3,10-dibromofascaplysin exhibited the highest selectivity, presumably due to the cytostatic effects executed via the targeting of cellular metabolism. Moreover, an introduction of radical substituents at C-9, C-10 or C-10 plus C-3 resulted in a notable reduction in DNA intercalating activity and improved selectivity. Taken together, our research contributes to understanding the structure-activity relationships of fascaplysin alkaloids and defines further directions of the structural optimization.

The biological screening of 44 marine sponge extracts for the research of bioactive molecules, with potential application in the treatment of age-related diseases (cancer and Alzheimer's disease) and skin aging, resulted in the selection of Scopalina hapalia extract for chemical study. As no reports of secondary metabolites of S. hapalia were found in the literature, we undertook this research to further extend current knowledge of Scopalina chemistry. The investigation of this species led to the discovery of four new compounds: two butenolides sinularone J (1) and sinularone K (2), one phospholipid 1-O-octadecyl-2-pentanoyl-sn-glycero-3-phosphocholine (3) and one lysophospholipid 1-O-(3-methoxy-tetradecanoyl)-sn-glycero-3-phosphocholine (4) alongside with known lysophospholipids (5 and 6), alkylglycerols (7-10), epidioxysterols (11 and 12) and diketopiperazines (13 and 14). The structure elucidation of the new metabolites (1-4) was determined by detailed spectroscopic analysis, including 1D and 2D NMR as well as mass spectrometry. Molecular networking was also explored to complement classical investigation and unravel the chemical classes within this species. GNPS analysis provided further information on potential metabolites with additional bioactive natural compounds predicted.

Two new cyclized thiolopyrrolone derivatives, namely, thiolopyrrolone A (1) and 2,2-dioxidothiolutin (2), together with the kn own compound, thiolutin (3) were identified from a marine-derived Streptomyces sp. BTBU20218885, which was isolated from a mud sample collected from the coastal region of Xiamen, China. Their chemical structures were determined using spectroscopic data, including HRESIMS, 1D and 2D NMR techniques. 1 possessed a unique unsymmetrical sulfur-containing thiolopyrrolone structure. All the compounds were tested for bioactivities against Staphylococcus aureus, Escherichia coli, Bacille Calmette-Guérin (BCG), Mycobacterium tuberculosis, and Candida albicans. 1 displayed antibacterial activities against BCG, M. tuberculosis, and S. aureus with minimum inhibitory concentration (MIC) values of 10, 10, and 100 μg/mL, respectively. Thiolutin (3) showed antibacterial activities against E. coli, BCG, M. tuberculosis, and S. aureus with MIC values of 6.25, 0.3125, 0.625, and 3.125 μg/mL, respectively.

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (-)-asperteretal G (1b), (+)-asperteretal H (2a), (-)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4-13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC50 = 25 μg/mL) and Klebsiella pneumoniae (IC50 = 50 μg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2-73.0% at a concentration of 50 μg/mL.

Four new dimeric sorbicillinoids (1-3 and 5) and a new monomeric sorbicillinoid (4) as well as six known analogs (6-11) were purified from the fungal strain Hypocrea jecorina H8, which was obtained from mangrove sediment, and showed potent inhibitory activity against the tea pathogenic fungus Pestalotiopsis theae (P. theae). The planar structures of 1-5 were assigned by analyses of their UV, IR, HR-ESI-MS, and NMR spectroscopic data. All the compounds were evaluated for growth inhibition of tea pathogenic fungus P. theae. Compounds 5, 6, 8, 9, and 10 exhibited more potent inhibitory activities compared with the positive control hexaconazole with an ED50 of 24.25 ± 1.57 µg/mL. The ED50 values of compounds 5, 6, 8, 9, and 10 were 9.13 ± 1.25, 2.04 ± 1.24, 18.22 ± 1.29, 1.83 ± 1.37, and 4.68 ± 1.44 µg/mL, respectively. Additionally, the effects of these compounds on zebrafish embryo development were also evaluated. Except for compounds 5 and 8, which imparted toxic effects on zebrafish even at 0.625 μM, the other isolated compounds did not exhibit significant toxicity to zebrafish eggs, embryos, or larvae. Taken together, sorbicillinoid derivatives (6, 9, and 10) from H. jecorina H8 displayed low toxicity and high anti-tea pathogenic fungus potential.

Four new benzodipyran racemates, namely (±)-aspergiletals A-D (3-6), representing a rare pyrano[4,3-h]chromene scaffold were isolated together with eurotiumide G (1) and eurotiumide F (2) from the soft-coral-derived fungus Aspergillus sp. EGF 15-0-3. All the corresponding optically pure enantiomers were successfully separated by a chiral HPLC column. The structures and configurations of all the compounds were elucidated based on the combination of NMR and HRESIMS data, chiral separation, single-crystal X-ray diffraction, quantum chemical 13C NMR, and electronic circular dichroism calculations. Meanwhile, the structure of eurotiumide G was also revised. The TDP1 inhibitor activities and photophysical properties of the obtained compounds were evaluated. In the TDP1 inhibition assay, as a result of synergy between (+)-6 and (-)-6, (±)-6 displayed strong inhibitory activity to TDP1 with IC50 values of 6.50 ± 0.73 μM. All compounds had a large Stokes shift and could be utilized for elucidating the mode of bioactivities by fluorescence imaging.

Seaweed endophytic (algicolous) fungi are talented producers of bioactive natural products. We have previously isolated two strains of the endophytic fungus, Pyrenochaetopsis sp. FVE-001 and FVE-087, from the thalli of the brown alga Fucus vesiculosus. Initial chemical studies yielded four new decalinoylspirotetramic acid derivatives with antimelanoma activity, namely pyrenosetins A-C (1-3) from Pyrenochaetopsis sp. strain FVE-001, and pyrenosetin D (4) from strain FVE-087. In this study, we applied a comparative metabolomics study employing HRMS/MS based feature-based molecular networking (FB MN) on both Pyrenochaetopsis strains. A higher chemical capacity in production of decalin derivatives was observed in Pyrenochaetopsis sp. FVE-087. Notably, several decalins showed different retention times despite the same MS data and MS/MS fragmentation pattern with the previously isolated pyrenosetins, indicating they may be their stereoisomers. FB MN-based targeted isolation studies coupled with antimelanoma activity testing on the strain FVE-087 afforded two new stereoisomers, pyrenosetins E (5) and F (6). Extensive NMR spectroscopy including DFT computational studies, HR-ESIMS, and Mosher's ester method were used in the structure elucidation of compounds 5 and 6. The 3'R,5'R stereochemistry determined for compound 6 was identical to that previously reported for pyrenosetin C (3), whose stereochemistry was revised as 3'S,5'R in this study. Pyrenosetin E (5) inhibited the growth of human malignant melanoma cells (A-375) with an IC50 value of 40.9 μM, while 6 was inactive. This study points out significant variations in the chemical repertoire of two closely related fungal strains and the versatility of FB MN in identification and targeted isolation of stereoisomers. It also confirms that the little-known fungal genus Pyrenochaetopsis is a prolific source of complex decalinoylspirotetramic acid derivatives.

Cone snail venom biodiversity reflects dietary preference and predatory and defensive envenomation strategies across the ≈900 species of Conidae. To better understand the mechanisms of adaptive radiations in closely related species, we investigated the venom of two phylogenetically and spatially related species, C. flavidus and C. frigidus of the Virgiconus clade. Transcriptomic analysis revealed that the major superfamily profiles were conserved between the two species, including 68 shared conotoxin transcripts. These shared transcripts contributed 90% of the conotoxin expression in C. frigidus and only 49% in C. flavidus, which showed greater toxin diversification in the dominant O1, I2, A, O2, O3, and M superfamilies compared to C. frigidus. On the basis of morphology, two additional sub-groups closely resembling C. flavidus were also identified from One Tree Island Reef. Despite the morphological resemblance, the venom duct proteomes of these cryptic sub-groups were distinct from C. flavidus. We suggest rapid conotoxin sequence divergence may have facilitated adaptive radiation and the establishment of new species and the regulatory mechanisms facilitating species-specific venom evolution.

This review highlights the underexplored potential and promises of marine bioactive peptides (MBPs) with unique structural, physicochemical, and biological activities to fight against the current and future human pathologies. A particular focus is given to the marine environment as a significant source to obtain or extract high-value MBPs from touched/untouched sources. For instance, marine microorganisms, including microalgae, bacteria, fungi, and marine polysaccharides, are considered prolific sources of amino acids at large, and peptides/polypeptides in particular, with fundamental structural sequence and functional entities of a carboxyl group, amine, hydrogen, and a variety of R groups. Thus, MBPs with tunable features, both structural and functional entities, along with bioactive traits of clinical and therapeutic value, are of ultimate interest to reinforce biomedical settings in the 21st century. On the other front, as the largest biome globally, the marine biome is the so-called "epitome of untouched or underexploited natural resources" and a considerable source with significant potentialities. Therefore, considering their biological and biomedical importance, researchers around the globe are redirecting and/or regaining their interests in valorizing the marine biome-based MBPs. This review focuses on the widespread bioactivities of MBPs, FDA-approved MBPs in the market, sustainable development goals (SDGs), and legislation to valorize marine biome to underlying the impact role of bioactive elements with the related pathways. Finally, a detailed overview of current challenges, conclusions, and future perspectives is also given to satisfy the stimulating demands of the pharmaceutical sector of the modern world.

This work studied the potential biotechnological applications of a naviculoid diatom (IMA053) and a green microalga (Tetraselmis marina IMA043) isolated from the North Adriatic Sea. Water, methanol, and dichloromethane (DCM) extracts were prepared from microalgae biomass and evaluated for total phenolic content (TPC) and in vitro antioxidant properties. Biomass was profiled for fatty acid methyl esters (FAME) composition. The DCM extracts had the highest levels of total phenolics, with values of 40.58 and 86.14 mg GAE/g dry weight (DW in IMA053 and IMA043, respectively). The DCM extracts had a higher radical scavenging activity (RSA) than the water and methanol ones, especially those from IMA043, with RSAs of 99.65% toward 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt (ABTS) at 10 mg/mL, and of 103.43% against 2,2-diphenyl-1-picrylhydrazyl (DPPH) at 5 mg/mL. The DCM extract of IMA053 displayed relevant copper chelating properties (67.48% at 10 mg/mL), while the highest iron chelating activity was observed in the water extract of the same species (92.05% at 10 mg/mL). Both strains presented a high proportion of saturated (SFA) and monounsaturated (MUFA) fatty acids. The results suggested that these microalgae could be further explored as sources of natural antioxidants for the pharmaceutical and food industry and as feedstock for biofuel production.

In recent years, the food, pharma, and cosmetic industries have shown considerable interest in bioactive molecules of marine origin that show high potential for application as nutraceuticals and therapeutic agents. Astaxanthin, a lipid-soluble and orange-reddish-colored carotenoid pigment, is one of the most investigated pigments. Natural astaxanthin is mainly produced from microalgae, and it shows much stronger antioxidant properties than its synthetic counterpart. This paper aims to summarize and discuss the important aspects and recent findings associated with the possible use of crustacean byproducts as a source of astaxanthin. In the last five years of research on the crustaceans and their byproducts as a source of natural astaxanthin, there are many new findings regarding the astaxanthin content in different species and new green extraction protocols for its extraction. However, there is a lack of information on the amounts of astaxanthin currently obtained from the byproducts as well as on the cost-effectiveness of the astaxanthin production from the byproducts. Improvement in these areas would most certainly contribute to the reduction of waste and reuse in the crustacean processing industry. Successful exploitation of byproducts for recovery of this valuable compound would have both environmental and social benefits. Finally, astaxanthin's strong biological activity and prominent health benefits have been discussed in the paper.

Through activity-guided fractionation, a new triterpene (asperflagin, 1) was isolated as a PPAR-γ agonist from the jellyfish-derived fungus Aspergillus flavus. Asperflagin displayed selective and moderate transactivation effects on PPAR-γ in Ac2F rat liver cells. Based on further biological evaluation and molecular docking analysis, we postulated that asperflagin might function as a PPAR-γ partial agonist. This compound was calculated to display a typical PPAR-γ ligand-receptor interaction that is distinct from that of full agonistic antidiabetics such as rosiglitazone, and may retain the antidiabetic effect without accompanying weight gain. Weight gain and obesity are typical side effects of the PPAR-γ full agonist rosiglitazone, and lead to suboptimal outcomes in diabetic patients. Compared to rosiglitazone, asperflagin showed higher glucose uptake in HepG2 human liver cells at concentrations of 20 and 40 μM but induced markedly lower adipogenesis and lipid accumulation in 3T3-L1 preadipocytes. These results suggest that asperflagin may be utilized for further study on advanced antidiabetic leads.

Wound healing is a highly orchestrated process involving many cell types, such as keratinocytes, fibroblasts and endothelial cells. This study aimed to evaluate the potential application of synthetic peptides derived from tilapia piscidin (TP)2, TP2-5 and TP2-6 in skin wound healing. The treatment of HaCaT keratinocytes with TP2-5 and TP2-6 did not cause cytotoxicity, but did enhance cell proliferation and migration, which could be attributed to the activation of epidermal growth factor receptor signaling. In CCD-966SK fibroblasts, although TP2-5 (31.25 μg/mL) and TP2-6 (125 μg/mL) showed cytotoxic effects, we observed the significant promotion of cell proliferation and migration at low concentrations. In addition, collagen I, collagen III, and keratinocyte growth factor were upregulated by the peptides. We further found that TP2-5 and TP2-6 showed pro-angiogenic properties, including the enhancement of human umbilical vein endothelial cell (HUVEC) migration and the promotion of neovascularization. In a murine model, wounds treated topically with TP2-5 and TP2-6 were reduced by day 2 post-injury and healed significantly faster than untreated wounds. Taken together, these findings demonstrate that both TP2-5 and TP2-6 have multifaceted effects when used as topical agents for accelerating wound healing.

The high-valued utilization of Ulva (previously known as Enteromorpha) bioresources has drawn increasing attention due to the periodic blooms of world-wide green tide. The polysaccharide is the main functional component of Ulva and exhibits various physiological activities. The Ulva oligosaccharide as the degradation product of polysaccharide not only possesses some obvious activities, but also possesses excellent solubility and bioavailability. Both Ulva polysaccharides and oligosaccharides hold promising potential in the food industry as new functional foods or food additives. Studies on Ulva polysaccharides and oligosaccharides are increasing and have been the focus of the marine bioresources field. However, the comprehensive review of this topic is still rare and do not cover the recent advances of the structure, isolation, preparation, activity and applications of Ulva polysaccharides and oligosaccharides. This review systematically summarizes and discusses the recent advances of chemical composition, extraction, purification, structure, and activity of Ulva polysaccharides as well as oligosaccharides. In addition, the potential applications as new functional food and food additives have also been considered, and these will definitely expand the applications of Ulva oligosaccharides in the food and medical fields.

Seal meat is of high nutritive value but is not highly exploited for human food due to ethical issues, undesirable flavors, and loss of nutrients during the processing/cooking step. In this work, commercially available processed seal meat was treated with its hydrolysates as preservatives with the aim of improving nutrient bioavailability. The contents of the nutrients were analyzed after digestion using a simulated dynamic digestion model, and the effects of different processing conditions, i.e., low-temperature processing and storage (25 °C) and high-temperature cooking (100 °C), of seal meat were investigated. Hydrolysates with antioxidant activity decreased the amounts of the less desirable Fe3+ ions in the seal meat digests. After treatment with hydrolysates at room temperature, a much higher total Fe content of 781.99 mg/kg was observed compared to other treatment conditions. The release of amino acids increased with temperature and was 520.54 mg/g for the hydrolysate-treated sample versus 413.12 mg/g for the control seal meat sample treated in buffer. Overall, this study provides useful data on the potential use of seal meat as a food product with high nutritive value and seal meat hydrolysates with antioxidant activity as preservatives to control oxidation in food.

We recently demonstrated the monthly variation and antioxidant activity of mycosporine-like amino acids (MAAs) from red alga dulse in Japan. The antioxidant activity of MAAs in acidic conditions was low compared to that in neutral and alkali conditions, but we found strong antioxidant activity from the heated crude MAA fraction in acidic conditions. In this study, we identified and characterized the key compounds involved in the antioxidant activity of this fraction. We first isolated two MAAs, palythine, and porphyra-334, from the fraction and evaluated the activities of the two MAAs when heated. MAAs possess absorption maxima at around 330 nm, while the heated MAAs lost this absorption. The heated MAAs showed a high ABTS radical scavenging activity at pH 5.8-8.0. We then determined the structure of heated palythine via ESI-MS and NMR analyses and speculated about the putative antioxidant mechanism. Finally, a suitable production condition of the heated compounds was determined at 120 °C for 30 min at pH 8.0. We revealed compounds from red algae with antioxidant activities at a wide range of pH values, and this information will be useful for the functional processing of food.

The loss of density and elasticity, the appearance of wrinkles and hyperpigmentation are among the first noticeable signs of skin aging. Beyond UV radiation and oxidative stress, matrix metalloproteinases (MMPs) assume a preponderant role in the process, since their deregulation results in the degradation of most extracellular matrix components. In this survey, four cyanobacteria strains were explored for their capacity to produce secondary metabolites with biotechnological potential for use in anti-aging formulations. Leptolyngbya boryana LEGE 15486 and Cephalothrix lacustris LEGE 15493 from freshwater ecosystems, and Leptolyngbya cf. ectocarpi LEGE 11479 and Nodosilinea nodulosa LEGE 06104 from marine habitats were sequentially extracted with acetone and water, and extracts were analyzed for their toxicity in cell lines with key roles in the skin context (HaCAT, 3T3L1, and hCMEC). The non-toxic extracts were chemically characterized in terms of proteins, carotenoids, phenols, and chlorophyll a, and their anti-aging potential was explored through their ability to scavenge the physiological free radical superoxide anion radical (O2•-), to reduce the activity of the MMPs elastase and hyaluronidase, to inhibit tyrosinase and thus avoid melanin production, and to block UV-B radiation (sun protection factor, SPF). Leptolyngbya species stood out for anti-aging purposes: L. boryana LEGE 15486 presented a remarkable SPF of 19 (at 200 µg/mL), being among the best species regarding O2•- scavenging, (IC50 = 99.50 µg/mL) and also being able to inhibit tyrosinase (IC25 = 784 µg/mL), proving to be promising against UV-induced skin-aging; L. ectocarpi LEGE 11479 was more efficient in inhibiting MMPs (hyaluronidase, IC50 = 863 µg/mL; elastase, IC50 = 391 µg/mL), thus being the choice to retard dermal density loss. Principal component analysis (PCA) of the data allowed the grouping of extracts into three groups, according to their chemical composition; the correlation of carotenoids and chlorophyll a with MMPs activity (p < 0.01), O2•- scavenging with phenolic compounds (p < 0.01), and phycocyanin and allophycocyanin with SPF, pointing to these compounds in particular as responsible for UV-B blockage. This original survey explores, for the first time, the biotechnological potential of these cyanobacteria strains in the field of skin aging, demonstrating the promising, innovative, and multifactorial nature of these microorganisms.