Phycobiliproteins (PBPs) are colored and water-soluble biliproteins found in cyanobacteria, rhodophytes, cryptomonads and cyanelles. They are divided into three main types: allophycocyanin, phycocyanin and phycoerythrin, according to their spectral properties. There are two methods for PBPs preparation. One is the extraction and purification of native PBPs from Cyanobacteria, Cryptophyta and Rhodophyta, and the other way is the production of recombinant PBPs by heterologous hosts. Apart from their function as light-harvesting antenna in photosynthesis, PBPs can be used as food colorants, nutraceuticals and fluorescent probes in immunofluorescence analysis. An increasing number of reports have revealed their pharmaceutical potentials such as antioxidant, anti-tumor, anti-inflammatory and antidiabetic effects. The advances in PBP biogenesis make it feasible to construct novel PBPs with various activities and produce recombinant PBPs by heterologous hosts at low cost. In this review, we present a critical overview on the productions, characterization and pharmaceutical potentials of PBPs, and discuss the key issues and future perspectives on the exploration of these valuable proteins.

Two new phenylhydrazone derivatives and one new alkaloid, penzonemycins A-B (1-2) and demethylmycemycin A (3), together with three known compounds including an alkaloid (4) and two sesquiterpenoids (5-6), were isolated from the Streptomyces sp. SCSIO 40020 obtained from the Pearl River Estuary sediment. Their structures and absolute configurations were assigned by 1D/2D NMR, mass spectroscopy and X-ray crystallography. Compound 1 was evaluated in four human cancer cell lines by the SRB method and displayed weak cytotoxicity in three cancer cell lines, with IC50 values that ranged from 30.44 to 61.92 µM, which were comparable to those of the positive control cisplatin. Bioinformatic analysis of the putative biosynthetic gene cluster indicated a Japp-Klingemann coupling reaction involved in the hydrazone formation of 1 and 2.

A new compound, exophilone (1), together with nine known compounds (2-10), were isolated from a deep-sea-derived fungus, Exophiala oligosperma. Their chemical structures, including the absolute configuration of 1, were elucidated using nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectroscopy (HRESIMS), and electronic circular dichroism (ECD) calculation. Compounds were preliminarily screened for their ability to inhibit collagen accumulation. Compounds 1, 4, and 7 showed weaker inhibition of TGF-β1-induced total collagen accumulation in compared with pirfenidone (73.14% inhibition rate). However, pirfenidone exhibited cytotoxicity (77.57% survival rate), while compounds 1, 4, and 7 showed low cytotoxicity against the HFL1 cell line. Particularly, exophilone (1) showed moderate collagen deposition inhibition effect (60.44% inhibition rate) and low toxicity in HFL1 cells (98.14% survival rate) at a concentration of 10 μM. A molecular docking study suggests that exophilone (1) binds to both TGF-β1 and its receptor through hydrogen bonding interactions. Thus, exophilone (1) was identified as a promising anti-pulmonary fibrosis agent. It has the potential to be developed as a drug candidate for pulmonary fibrosis.

Algae accumulate large amounts of polysaccharides in their cell walls or intercellular regions. Polysaccharides from algae possess high potential as promising candidates for marine drug development. In this study, a sulfated polysaccharide, UCP, from the green alga Ulva conglobata Kjellman was obtained by water extraction, anion-exchange, and size-exclusion chromatography purification, and its structure was characterized by a combination of chemical and spectroscopic methods. UCP mainly consisted of →4)-α/β-l-Rhap-(1→, →4)-β-d-Xylp-(1→ and →4)-β-d-GlcAp-(1→ residues. Sulfate ester groups were substituted mainly at C-3 of →4)-l-Rhap-(1→ and C-2 of →4)-β-d-Xylp-(1→. Partial glycosylation was at C-2 of →4)-α-l-Rhap-(1→ residues. UCP possessed a potent immunomodulatory effect in vitro, evaluated by the assays of lymphocyte proliferation and macrophage phagocytosis. The immunomodulatory activity of UCP in vivo was further investigated using immunosuppressive mice induced by cyclophosphamide. The results showed that UCP markedly increased the spleen and thymus indexes and ameliorated the cyclophosphamide-induced damage to the spleen and thymus. UCP could increase the levels of white blood cells, lymphocytes, and platelets, and improve the hematopoietic inhibition caused by cyclophosphamide. Moreover, UCP significantly promoted the secretions of the immunoglobulin (Ig)G, IgE, and IgM. The data demonstrated that UCP is a novel sulfated polysaccharide and may be a promising immunomodulatory agent.

Driven by consumer demand and government policies, synthetic additives in aquafeed require substitution with sustainable and natural alternatives. Seaweeds have been shown to be a sustainable marine source of novel bioactive phenolic compounds that can be used in food, animal and aqua feeds, or microencapsulation applications. For example, phlorotannins are a structurally unique polymeric phenolic group exclusively found in brown seaweed that act through multiple antioxidant mechanisms. Seaweed phenolics show high affinities for binding proteins via covalent and non-covalent bonds and can have specific bioactivities due to their structures and associated physicochemical properties. Their ability to act as protein cross-linkers means they can be used to enhance the rheological and mechanical properties of food-grade delivery systems, such as microencapsulation, which is a new area of investigation illustrating the versatility of seaweed phenolics. Here we review how seaweed phenolics can be used in a range of applications, with reference to their bioactivity and structural properties.

Fucoxanthin is a marine carotenoid found in brown seaweeds and several microalgae. It has been reported that fucoxanthin has health benefits such as anti-obesity and anti-diabetic effects. To facilitate fucoxanthin applications in the food industry, it is important to improve its low bioavailability. We attempted the combined feeding of fucoxanthin-containing seaweed oil (SO) and monocaprin in a powder diet and analyzed the fucoxanthin metabolite contents in the liver, small intestine and serum of diabetic/obese KK-Ay mice. After 4 weeks of feeding with the experimental diets, the serum fucoxanthinol concentrations of the mice fed 0.2% SO and 0.5% monocaprin were higher than those of the 0.2% SO-fed mice. Furthermore, fucoxanthinol accumulation in the liver and small intestine tended to increase in a combination diet of 0.2% SO and 0.125-0.5% monocaprin compared with a diet of 0.2% SO alone, although amarouciaxanthin A accumulation was not different among the 0.2% SO-fed groups. These results suggest that a combination of monocaprin with fucoxanthin-containing SO is an effective treatment for improving the bioavailability of fucoxanthin.

BACKGROUND: Chitosan oligosaccharides, with an average molecular weight ≤ 1000 Da (COST), is a natural marine product that has the potential to improve intestinal microflora and resist lipid metabolism disorders. METHODS: First, by establishing a mice model of lipid metabolism disorder induced by a high fat and high sugar diet, it is proven that COST can reduce lipid metabolism disorder, which may play a role in regulating intestinal microorganisms. Then, the key role of COST in the treatment of intestinal microorganisms is further confirmed through the method of COST-treated feces and fecal bacteria transplantation. CONCLUSIONS: intestinal microbiota plays a key role in COST inhibition of lipid metabolism disorder induced by a high fat and high sugar diet. In particular, COST may play a central regulatory role in microbiota, including Bacteroides, Akkermansia, and Desulfovibrio. Taken together, our work suggests that COST may improve the composition of gut microbes, increase the abundance of beneficial bacteria, improve lipid metabolism disorders, and inhibit the development of metabolic disorders.

Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G-J (1-4), and five known analogs (5-9) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1-9 exhibited strong antifungal activities against Colletotrichum gloeosporioides with LD50 values from 0.61 μg/mL to 16.14 μg/mL. Meanwhile, all compounds were evaluated for their cytotoxic activities against human pancreatic cancer BXPC-3 and PANC-1 cell lines; as a result, compound 1 showed more significant cytotoxicities than the positive control against both cell lines. In addition, based on the analyses of the protein-protein interaction (PPI) network and Western blot, 1 could induce apoptosis by activating caspase 3 proteins (CASP3).

The carotenoids, including lycopene, lutein, astaxanthin, and zeaxanthin belong to the isoprenoids, whose basic structure is made up of eight isoprene units, resulting in a C40 backbone, though some of them are only trace components in Euglena. They are essential to all photosynthetic organisms due to their superior photoprotective and antioxidant properties. Their dietary functions decrease the risk of breast, cervical, vaginal, and colorectal cancers and cardiovascular and eye diseases. Antioxidant functions of carotenoids are based on mechanisms such as quenching free radicals, mitigating damage from reactive oxidant species, and hindering lipid peroxidation. With the development of carotenoid studies, their distribution, functions, and composition have been identified in microalgae and higher plants. Although bleached or achlorophyllous mutants of Euglena were among the earliest carotenoid-related microalgae under investigation, current knowledge on the composition and biosynthesis of these compounds in Euglena is still elusive. This review aims to overview what is known about carotenoid metabolism in Euglena, focusing on the carotenoid distribution and structure, biosynthesis pathway, and accumulation in Euglena strains and mutants under environmental stresses and different culture conditions. Moreover, we also summarize the potential applications in therapy preventing carcinogenesis, cosmetic industries, food industries, and animal feed.

Conopeptides are peptides in the venom of marine cone snails that are used for capturing prey or as a defense against predators. A new cysteine-poor conopeptide, Czon1107, has exhibited non-competitive inhibition with an undefined allosteric mechanism in the human (h) α3β4 nicotinic acetylcholine receptors (nAChRs). In this study, the binding mode of Czon1107 to hα3β4 nAChR was investigated using molecular dynamics simulations coupled with mutagenesis studies of the peptide and electrophysiology studies on heterologous hα3β4 nAChRs. Overall, this study clarifies the structure-activity relationship of Czon1107 and hα3β4 nAChR and provides an important experimental and theoretical basis for the development of new peptide drugs.

Fungi fibrinolytic compound 1 (FGFC1) is a rare pyran-isoindolone derivative with fibrinolytic activity. The aim of this study was to further determine the effect of FGFC1 on fibrin clots lysis in vitro. We constructed a fibrinolytic system containing single-chain urokinase-type plasminogen activator (scu-PA) and plasminogen to measure the fibrinolytic activity of FGFC1 using the chromogenic substrate method. After FITC-fibrin was incubated with increasing concentrations of FGFC1, the changes in the fluorescence intensity and D-dimer in the lysate were measured using a fluorescence microplate reader. The fibrin clot structure induced by FGFC1 was observed and analyzed using a scanning electron microscope and laser confocal microscope. We found that the chromogenic reaction rate of the mixture system increased from (15.9 ± 1.51) × 10-3 min-1 in the control group to (29.7 ± 1.25) × 10-3 min-1 for 12.8 μM FGFC1(p < 0.01). FGFC1 also significantly increased the fluorescence intensity and d-dimer concentration in FITC fibrin lysate. Image analysis showed that FGFC1 significantly reduced the fiber density and increased the fiber diameter and the distance between protofibrils. These results show that FGFC1 can effectively promote fibrin lysis in vitro and may represent a novel candidate agent for thrombolytic therapy.

Antibody-drug conjugates (ADCs) are an important class of therapeutics for the treatment of cancer. Structurally, an ADC comprises an antibody, which serves as the delivery system, a payload drug that is a potent cytotoxin that kills cancer cells, and a chemical linker that connects the payload with the antibody. Unlike conventional chemotherapy methods, an ADC couples the selective targeting and pharmacokinetic characteristics related to the antibody with the potent cytotoxicity of the payload. This results in high specificity and potency by reducing off-target toxicities in patients by limiting the exposure of healthy tissues to the cytotoxic drug. As a consequence of these outstanding features, significant research efforts have been devoted to the design, synthesis, and development of ADCs, and several ADCs have been approved for clinical use. The ADC field not only relies upon biology and biochemistry (antibody) but also upon organic chemistry (linker and payload). In the latter, total synthesis of natural and designed cytotoxic compounds, together with the development of novel synthetic strategies, have been key aspects of the consecution of clinical ADCs. In the case of payloads from marine origin, impressive structural architectures and biological properties are observed, thus making them prime targets for chemical synthesis and the development of ADCs. In this review, we explore the molecular and biological diversity of ADCs, with particular emphasis on those containing marine cytotoxic drugs as the payload.

Echinoderms belong to the phylum Echinodermata (from the Ancient Greek words "echinos" (hedgehog) and "derma" (skin)) [...].

Antioxidant compounds decrease the amount of intracellular reactive oxygen species (ROS) and, consequently, reduce the deleterious effects of ROS in osteoblasts. Here, we modified a 21 kDa fucoidan (FucA) with gallic acid (GA) using the redox method, to potentiate its antioxidant/protective capacity on pre-osteoblast-like cells (MC3T3) against oxidative stress. The 20 kDa FucA-GA contains 37 ± 3.0 mg GA per gram of FucA. FucA-GA was the most efficient antioxidant agent in terms of total antioxidant capacity (2.5 times), reducing power (five times), copper chelation (three times), and superoxide radical scavenging (2 times). Exposure of MC3T3 cells to H2O2 increased ROS levels and activated caspase-3 along with caspase-9. In addition, the cell viability decreased approximately 80%. FucA-GA also provided the most effective protection against oxidative damage caused by H2O2. Treatment with FucA-GA (1.0 mg/mL) increased cell viability (~80%) and decreased intracellular ROS (100%) and caspase activation (~80%). In addition, Fuc-GA (0.1 mg/mL) abolished H2O2-induced oxidative stress in zebra fish embryos. Overall, FucA-GA protected MC3T3 cells from oxidative stress and could represent a possible adjuvant for the treatment of bone fragility by counteracting oxidative phenomena.

Sleep deficiency is now considered an emerging global epidemic associated with many serious health problems, and a major cause of financial and social burdens. Sleep and mental health are closely connected, further exacerbating the negative impact of sleep deficiency on overall health and well-being. A major drawback of conventional treatments is the wide range of undesirable side-effects typically associated with benzodiazepines and antidepressants, which can be more debilitating than the initial disorder. It is therefore valuable to explore the efficiency of other remedies for complementarity and synergism with existing conventional treatments, leading to possible reduction in undesirable side-effects. This review explores the relevance of microalgae bioactives as a sustainable source of valuable phytochemicals that can contribute positively to mood and sleep disorders. Microalgae species producing these compounds are also catalogued, thus creating a useful reference of the state of the art for further exploration of this proposed approach. While we highlight possibilities awaiting investigation, we also identify the associated issues, including minimum dose for therapeutic effect, bioavailability, possible interactions with conventional treatments and the ability to cross the blood brain barrier. We conclude that physical and biological functionalization of microalgae bioactives can have potential in overcoming some of these challenges.

Carotenoid xanthophyll pigments are receiving growing interest in various industrial fields due to their broad and diverse bioactive and health beneficial properties. Fucoxanthin (Fx) and the inter-convertible couple diadinoxanthin-diatoxanthin (Ddx+Dtx) are acknowledged as some of the most promising xanthophylls; they are mainly synthesized by diatoms (Bacillariophyta). While temperate strains of diatoms have been widely investigated, recent years showed a growing interest in using polar strains, which are better adapted to the natural growth conditions of Nordic countries. The aim of the present study was to explore the potential of the polar diatom Fragilariopsis cylindrus in producing Fx and Ddx+Dtx by means of the manipulation of the growth light climate (daylength, light intensity and spectrum) and temperature. We further compared its best capacity to the strongest xanthophyll production levels reported for temperate counterparts grown under comparable conditions. In our hands, the best growing conditions for F. cylindrus were a semi-continuous growth at 7 °C and under a 12 h light:12 h dark photoperiod of monochromatic blue light (445 nm) at a PUR of 11.7 μmol photons m-2 s-1. This allowed the highest Fx productivity of 43.80 µg L-1 day-1 and the highest Fx yield of 7.53 µg Wh-1, more than two times higher than under 'white' light. For Ddx+Dtx, the highest productivity (4.55 µg L-1 day-1) was reached under the same conditions of 'white light' and at 0 °C. Our results show that F. cylindrus, and potentially other polar diatom strains, are very well suited for Fx and Ddx+Dtx production under conditions of low temperature and light intensity, reaching similar productivity levels as model temperate counterparts such as Phaeodactylum tricornutum. The present work supports the possibility of using polar diatoms as an efficient cold and low light-adapted bioresource for xanthophyll pigments, especially usable in Nordic countries.

The survival selection pressure caused by antibiotic-mediated bactericidal and bacteriostatic activity is one of the important inducements for bacteria to develop drug resistance. Bacteria gain drug resistance through spontaneous mutation so as to achieve the goals of survival and reproduction. Quorum sensing (QS) is an intercellular communication system based on cell density that can regulate bacterial virulence and biofilm formation. The secretion of more than 30 virulence factors of P. aeruginosa is controlled by QS, and the formation and diffusion of biofilm is an important mechanism causing the multidrug resistance of P. aeruginosa, which is also closely related to the QS system. There are three main QS systems in P. aeruginosa: las system, rhl system, and pqs system. Quorum-sensing inhibitors (QSIs) can reduce the toxicity of bacteria without affecting the growth and enhance the sensitivity of bacterial biofilms to antibiotic treatment. These characteristics make QSIs a popular topic for research and development in the field of anti-infection. This paper reviews the research progress of the P. aeruginosa quorum-sensing system and QSIs, targeting three QS systems, which will provide help for the future research and development of novel quorum-sensing inhibitors.

Three new polyketides, eutyketides A and B (1 and 2) and cytosporin X (3), along with four known compounds (4-7), were obtained from the marine-derived fungus Eutypella scoparia. The planar structures of 1 and 2 were elucidated by extensive HRMS and 1D and 2D NMR analyses. Their relative configurations of C-13 and C-14 were determined with chemical conversions by introducing an acetonylidene group. The absolute configurations of 1-3 were determined by comparing their experimental electronic circular dichroism (ECD) data with their computed ECD results. All of the isolated compounds were tested for their anti-inflammatory activities on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages. Compounds 5 and 6 showed stronger anti-inflammatory activities than the other compounds, with the inhibition of 49.0% and 54.9% at a concentration of 50.0 µg/mL, respectively.

A series of phenolic acid chitooligosaccharide (COS) derivatives synthesized by two mild and green methods were illuminated in this paper. Seven phenolic acids were selected to combine two kinds of COS derivatives: the phenolic acid chitooligosaccharide salt derivatives and the phenolic-acid-acylated chitooligosaccharide derivatives. The structures of the derivatives were characterized by FT-IR and 1H NMR spectra. The antioxidant experiment results in vitro (including DPPH-radical scavenging activity, superoxide-radical scavenging activity, hydroxyl-radical scavenging ability, and reducing power) demonstrated that the derivatives exhibited significantly enhanced antioxidant activity compared to COS. Moreover, the study showed that the phenolic acid chitooligosaccharide salts had stronger antioxidant activity than phenolic-acid-acylated chitooligosaccharide. The cytotoxicity assay of L929 cells in vitro indicated that the derivatives had low cytotoxicity and good biocompatibility. In conclusion, this study provides a possible synthetic method for developing novel and nontoxic antioxidant agents which can be used in the food and cosmetics industry.

Microalgae are photosynthetic organisms known for producing valuable metabolites under different conditions such as extreme temperatures, high salinity, osmotic pressure, and ultraviolet radiation. In recent years, these metabolites have become a trend due to their versatility in applications such as pharmaceuticals, cosmetics, and others. They have even been proposed as an alternative source of bioactive metabolites to avoid the harmful effects on the environment produced by active compounds such as oxybenzone in commercials sunscreens. One of the most studied applications is the use of microalgae for skin care and topical use as cosmeceuticals. With the increasing demand for more environmentally friendly products in cosmetics, microalgae have been further explored in relation to this application. It has been shown that some microalgae are resistant to UV rays due to certain compounds such as mycosporine-like amino acids, sporopollenin, scytonemin, and others. These compounds have different mechanisms of action to mitigate UV damage induced. Still, they all have been proven to confer UV tolerance to microalgae with an absorbance spectrum like the one in conventional sunscreens. This review focuses on the use of these microalgae compounds obtained by UV stimulation and takes advantage of their natural UV-resistant characteristics to potentially apply them as an alternative for UV protection products.

To solve the problem of antibiotic abuse in aquaculture and to utilize the application potential of antimicrobial peptides (AMPs), a chloroplast transformation system of Porphyridium purpureum was successfully constructed for effectively expressing two exogenous AMPs. The endogenous fragments of 16S rDNA/trnA-23S rDNA were used as flanking fragments for the homologous recombination in the chloroplast genome. Two AMPs encoded by the transformation vector were controlled by the native promoter psbB in a polycistron. The plasmids were transferred into P. purpureum via particle bombardment and the transformation vectors were screened using phosphinothricin (bar), a dominant selection marker under the control of the psbA promoter. Subsequently, in the positive transformed colonies, the exogenous fragments were found to be inserted in the flanking fragments directionally as expected and two foreign AMPs were successfully obtained. Finally, two exogenous peptides with antibacterial properties were obtained from the transformed strain. The two AMPs expressed by the transformed strain were shown to have similar inhibitory effects to antibiotics by inhibition tests. This suggested that AMPs can be introduced into aquaculture using baited microalgae, providing new ideas and ways to solve a series of aquaculture diseases caused by bacteria.

Symbiotic relationships are very important for corals. Abiotic stressors cause the acclimatization of cell membranes in symbionts, which possess different membrane acclimatization strategies. Membrane stability is determined by a unique lipid composition and, thus, the profile of thylakoid lipids can depend on coral symbiont species. We have analyzed and compared thylakoid lipidomes (mono- and digalactosyldiacylglycerols (MGDG and DGDG), sulfoquinovosyldiacylglycerols (SQDG), and phosphatidylglycerols (PG)) of crude extracts from symbiotic reef-building coral Acropora sp., the hydrocoral Millepora platyphylla, and the octocoral Sinularia flexibilis. S. flexibilis crude extracts were characterized by a very high SQDG/PG ratio, a DGDG/MGDG ratio < 1, a lower degree of galactolipid unsaturation, a higher content of SQDG with polyunsaturated fatty acids, and a thinner thylakoid membrane which may be explained by the presence of thermosensitive dinoflagellates Cladocopium C3. In contrast, crude extracts of M. platyphylla and Acropora sp. exhibited the lipidome features of thermotolerant Symbiodiniaceae. M. platyphylla and Acropora sp. colonies contained Cladocopium C3u and Cladocopium C71/C71a symbionts, respectively, and their lipidome profiles showed features that indicate thermotolerance. We suggest that an association with symbionts that exhibit the thermotolerant thylakoid lipidome features, combined with a high Symbiodiniaceae diversity, may facilitate further acclimatization/adaptation of M. platyphylla and Acropora sp. holobionts in the South China Sea.

Mesoporous silica nanoparticles (MSNs) have great potential for applications as a drug delivery system (DDS) due to their unique properties such as large pore size, high surface area, biocompatibility, biodegradability, and stable aqueous dispersion. The MSN-mediated DDS can carry chemotherapeutic agents, optical sensors, photothermal agents, short interfering RNA (siRNA), and gene therapeutic agents. The MSN-assisted imaging techniques are applicable in cancer diagnosis. However, their synthesis via a chemical route requires toxic chemicals and is challenging, time-consuming, and energy-intensive, making the process expensive and non-viable. Fortunately, nature has provided a viable alternative material in the form of biosilica from marine resources. In this review, the applications of biosilica nanoparticles synthesized from marine diatoms in the field of drug delivery, biosensing, imaging agents, and regenerative medicine, are highlighted. Insights into the use of biosilica in the field of DDSs are elaborated, with a focus on different strategies to improve the physico-chemical properties with regards to drug loading and release efficiency, targeted delivery, and site-specific binding capacity by surface functionalization. The limitations, as well as the future scope to develop them as potential drug delivery vehicles and imaging agents, in the overall therapeutic management, are discussed.

The current mindset in the cosmetics market about sustainable ingredients had increased the search for new sources of natural active ingredients. Cyanobacteria are a great source of functional ingredients for cosmetics, as a producer of pigments with described bioactive potential (carotenoids and phycobiliproteins). This work aimed to evaluate the cosmetic potential of marine cyanobacterium Cyanobium sp. pigment-targeted extracts (carotenoids and phycobiliproteins), evaluating their in vitro safety through cytotoxicity assays, cosmetic-related enzyme inhibition, ingredient stability, and putative product (serum formulation). Results showed no cytotoxicity from the extracts in skin-related cell lines. Carotenoid extract showed anti-hyaluronidase capacity (IC50 = 108.74 ± 5.74 mg mL-1) and phycobiliprotein extract showed anti-hyaluronidase and anti-collagenase capacity (IC50 = 67.25 ± 1.18 and 582.82 ± 56.99 mg mL-1, respectively). Regarding ingredient and serum stability, both ingredients showed higher stability at low-temperature conditions, and it was possible to maintain the pigment content and bioactive capacity stable during the tested period, although in higher temperatures the product was degraded in a week. As a major conclusion, both extracts can be potential natural and sustainable ingredients for cosmetic uses, with relatively simple formulation and storage, and can be promising natural anti-aging ingredients due to their bioactive capacity.

Overexpressed EGFR and mutant K-Ras play vital roles in therapeutic resistance in colorectal cancer patients. To search for an effective therapeutic protocol is an urgent task. A secondary metabolite in the sponge Hippospongia sp., Heteronemin, has been shown to induce anti-proliferation in several types of cancers. A thyroxine-deaminated analogue, tetrac, binds to integrin αvβ3 to induce anti-proliferation in different cancers. Heteronemin- and in combination with tetrac-induced antiproliferative effects were evaluated. Tetrac enhanced heteronemin-induced anti-proliferation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC). Heteronemin and tetrac arrested cell cycle in different phases. Combined treatment increased the cell accumulation in sub-G1 and S phases. The combined treatment also induced the inactivation of EGFR signaling and downregulated the phosphorylated ERK1/2 protein in both cell lines. Heteronemin and the combination showed the downregulation of the phosphorylated and total PI3K protein in HT-29 cells (KRAS WT CRC). Results by NanoString technology and RT-qPCR revealed that heteronemin and combined treatment suppressed the expression of EGFR and downstream genes in HCT-116 cells (KRAS MT CRC). Heteronemin or combined treatment downregulated genes associated with cancer progression and decreased cell motility. Heteronemin or the combined treatment suppressed PD-L1 expression in both cancer cell lines. However, only tetrac and the combined treatment inhibited PD-L1 protein accumulation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC), respectively. In summary, heteronemin induced anti-proliferation in colorectal cancer cells by blocking the EGFR-dependent signal transduction pathway. The combined treatment further enhanced the anti-proliferative effect via PD-L1 suppression. It can be an alternative strategy to suppress mutant KRAS resistance for anti-EGFR therapy.

Obesity increases the risks of metabolic syndromes including nonalcoholic fatty liver disease (NAFLD), diabetic dyslipidemia, and chronic kidney disease. Dietary krill oil (KO) has shown antioxidant and anti-inflammatory properties, thereby being a therapeutic potential for obesity-induced metabolic syndromes. Thus, the effects of KO on lipid metabolic alteration were examined in a high-fat diet (HFD)-fed mice model. The HFD model (n = 10 per group) received an oral gavage with distilled water as a control, metformin at 250 mg/kg, and KO at 400, 200, and 100 mg/kg for 12 weeks. The HFD-induced weight gain and fat deposition were significantly reduced in the KO treatments compared with the control. Blood levels were lower in parameters for NAFLD (e.g., alanine aminotransferase, and triglyceride), type 2 diabetes (e.g., glucose and insulin), and renal dysfunction (e.g., blood urea nitrogen and creatinine) by the KO treatments. The KO inhibited lipid synthesis through the modification of gene expressions in the liver and adipose tissues and adipokine-mediated pathways. Furthermore, KO showed hepatic antioxidant activities and glucose lowering effects. Histopathological analyses revealed that the KO ameliorated the hepatic steatosis, pancreatic endocrine/exocrine alteration, adipose tissue hypertrophy, and renal steatosis. These analyses suggest that KO may be promising for inhibiting obesity and metabolic syndromes.

Mycosporine-like amino acids (MAAs) are small molecules with robust ultraviolet (UV)-absorbing capacities and a huge potential to be used as an environmentally friendly natural sunscreen. MAAs, temperature, and light-stable compounds demonstrate powerful photoprotective capacities and the ability to capture light in the UV-A and UV-B ranges without the production of damaging free radicals. The biotechnological uses of these secondary metabolites have been often limited by the small quantities restored from natural resources, variation in MAA expression profiles, and limited success in heterologous expression systems. Overcoming these obstacles requires a better understanding of MAA biosynthesis and its regulatory processes. MAAs are produced to a certain extent via a four-enzyme pathway, including genes encoding enzymes dehydroquinate synthase, enzyme O-methyltransferase, adenosine triphosphate grasp, and a nonribosomal peptide synthetase. However, there are substantial genetic discrepancies in the MAA genetic pathway in different species, suggesting further complexity of this pathway that is yet to be fully explored. In recent years, the application of genome-mining approaches allowed the identification of biosynthetic gene clusters (BGCs) that resulted in the discovery of many new compounds from unconventional sources. This review explores the use of novel genomics tools for linking BGCs and secondary metabolites based on the available omics data, including MAAs, and evaluates the potential of using novel genome-mining tools to reveal a cryptic potential for new bioproduct screening approaches and unrevealing new MAA producers.

The applications of alginate lyase are diverse, but efficient commercial enzymes are still unavailable. In this study, a novel alginate lyase with high activity was obtained from the marine bacteria Vibrio sp. Ni1. The ORF of the algB gene has 1824 bp, encoding 607 amino acids. Homology analysis shows that AlgB belongs to the PL7 family. There are two catalytic domains with the typical region of QIH found in AlgB. The purified recombinant enzyme of AlgB shows highest activity at 35 °C, pH 8.0, and 50 mmol/L Tris-HCl without any metal ions. Only K+ slightly enhances the activity, while Fe2+ and Cu2+ strongly inhibit the activity. The AlgB preferred polyM as substrate. The end products of enzymatic mixture are DP2 and DP3, without any metal ion to assist them. This enzyme has good industrial application prospects.

Anthraquinones are an interesting chemical class of polyketides since they not only exhibit a myriad of biological activities but also contribute to managing ecological roles. In this review article, we provide a current knowledge on the anthraquinoids reported from marine-derived fungi, isolated from various resources in both shallow waters such as mangrove plants and sediments of the mangrove habitat, coral reef, algae, sponges, and deep sea. This review also tentatively categorizes anthraquinone metabolites from the simplest to the most complicated scaffolds such as conjugated xanthone-anthraquinone derivatives and bianthraquinones, which have been isolated from marine-derived fungi, especially from the genera Apergillus, Penicillium, Eurotium, Altenaria, Fusarium, Stemphylium, Trichoderma, Acremonium, and other fungal strains. The present review, covering a range from 2000 to 2021, was elaborated through a comprehensive literature search using the following databases: ACS publications, Elsevier, Taylor and Francis, Wiley Online Library, MDPI, Springer, and Thieme. Thereupon, we have summarized and categorized 296 anthraquinones and their derivatives, some of which showed a variety of biological properties such as enzyme inhibition, antibacterial, antifungal, antiviral, antitubercular (against Mycobacterium tuberculosis), cytotoxic, anti-inflammatory, antifouling, and antioxidant activities. In addition, proposed biogenetic pathways of some anthraquinone derivatives are also discussed.

Acquired immunodeficiency syndrome (AIDS) is a chronic and potentially fatal ailment caused by the human immunodeficiency virus (HIV) and remains a major health problem worldwide. In recent years, the research focus has shifted to a greater emphasis on complementing treatment regimens involving conventional antiretroviral (ARV) drug therapies with novel lead structures isolated from various marine organisms that have the potential to be utilized as therapeutics for the management of HIV-AIDS. The present review summarizes the recent developments regarding bioactive peptides sourced from various marine organisms. This includes a discussion encompassing the potential of these novel marine bioactive peptides with regard to antiretroviral activities against HIV, preparation, purification, and processing techniques, in addition to insight into the future trends with an emphasis on the potential of exploration and evaluation of novel peptides to be developed into effective antiretroviral drugs.

New carboxamides, (±)-vochysiamide C (1) and (+)-vochysiamide B (2), and a new polyketide, 4S,3aS,9aR-3a,9a-deoxy-3a hydroxy-1-dehydroxyarthrinone (3), were isolated and identified from the sponge-derived fungus Arthrinium sp. SCSIO 41421, together with other fifteen known natural products (4-18). Their structures including absolute configurations were determined by detailed NMR, MS spectroscopic analyses, calculated electronic circular dichroism (ECD), as well as quantum-chemical NMR calculations. Preliminary bioactivity screening and molecular docking analysis revealed that several natural products exhibited obvious enzyme inhibitory activities against acetylcholinesterase (AChE), such as 2,3,6,8-tetrahydroxy-1-methylxanthone (4) with an inhibitory rate 86% at 50 μg/mL.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer and exhibits a devastating 5-year survival rate. The most recent procedure for the treatment of PDAC is a combination of several conventional chemotherapeutic agents, termed FOLFIRINOX, that includes irinotecan, leucovorin, oxaliplatin, and 5-fluorouracil (5-FU). However, ongoing treatment using these agents is challenging due to their severe side effects and limitations on the range of patients available for PDAC. Therefore, safer and more innovative anticancer agents must be developed. The anticarcinoma activity of matairesinol that can be extracted from seagrass has been reported in various types of cancer, including prostate, breast, cervical, and pancreatic cancer. However, the molecular mechanism of effective anticancer activity of matairesinol against pancreatic cancer remains unclear. In the present study, we confirmed the inhibition of cell proliferation and progression induced by matairesinol in representative human pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). Additionally, matairesinol triggers apoptosis and causes mitochondrial impairment as evidenced by the depolarization of the mitochondrial membrane, disruption of calcium, and suppression of cell migration and related intracellular signaling pathways. Finally, matairesinol exerts a synergistic effect with 5-FU, a standard anticancer agent for PDAC. These results demonstrate the therapeutic potential of matairesinol in the treatment of PDAC.

Nowadays, the therapeutic efficiency of small interfering RNAs (siRNA) is still limited by the efficiency of gene therapy vectors capable of carrying them inside the target cells. In this study, siRNA nanocarriers based on low molecular weight chitosan grafted with increasing proportions (5 to 55%) of diisopropylethylamine (DIPEA) groups were developed, which allowed precise control of the degree of ionization of the polycations at pH 7.4. This approach made obtaining siRNA nanocarriers with small sizes (100-200 nm), positive surface charge and enhanced colloidal stability (up to 24 h) at physiological conditions of pH (7.4) and ionic strength (150 mmol L-1) possible. Moreover, the PEGylation improved the stability of the nanoparticles, which maintained their colloidal stability and nanometric sizes even in an albumin-containing medium. The chitosan-derivatives displayed non-cytotoxic effects in both fibroblasts (NIH/3T3) and macrophages (RAW 264.7) at high N/P ratios and polymer concentrations (up to 0.5 g L-1). Confocal microscopy showed a successful uptake of nanocarriers by RAW 264.7 macrophages and a promising ability to silence green fluorescent protein (GFP) in HeLa cells. These results were confirmed by a high level of tumor necrosis factor-α (TNFα) knockdown (higher than 60%) in LPS-stimulated macrophages treated with the siRNA-loaded nanoparticles even in the FBS-containing medium, findings that reveal a good correlation between the degree of ionization of the polycations and the physicochemical properties of nanocarriers. Overall, this study provides an approach to enhance siRNA condensation by chitosan-based carriers and highlights the potential of these nanocarriers for in vivo studies.

Filter-feeding bivalves can accumulate paralytic shellfish toxins (PST) produced by toxic microalgae, which may induce oxidative stress and lipid peroxidation. Peroxisomal acyl-coenzyme A oxidases (ACOXs) are key enzymes functioning in maintaining redox and lipid homeostasis, but their roles in PST response in bivalves are less understood. Herein, a total of six and six ACOXs were identified in the Chlamys farreri and Patinopecten yessoensis genome, respectively, and the expansion of ACOX1s was observed. Gene expression analysis revealed an organ/tissue-specific expression pattern in both scallops, with all ACOXs being predominantly expressed in the two most toxic organs, digestive glands and kidneys. The regulation patterns of scallop ACOXs after exposure to different PST-producing algaes Alexandrium catenella (ACDH) and A. minutum (AM-1) were revealed. After ACDH exposure, more differentially expressed genes (DEGs) were identified in C. farreri digestive glands (three) and kidneys (five) than that in P. yessoensis (two), but the up-regulated DEGs showed similar expression patterns in both species. In C. farreri, three DEGs were found in both digestive glands and kidneys after AM-1 exposure, with two same CfACOX1s being acutely and chronically induced, respectively. Notably, these two CfACOX1s also showed different expression patterns in kidneys between ACDH (acute response) and AM-1 (chronic response) exposure. Moreover, inductive expression of CfACOXs after AM-1 exposure was observed in gills and mantles, and all DEGs in both tissues were up-regulated and their common DEGs exhibited both acute and chronic induction. These results indicate the involvement of scallop ACOXs in PST response, and their plasticity expression patterns between scallop species, among tissues, and between the exposure of different PST analogs.

Sulfated polysaccharides (SPS) from seaweeds have great biochemical and biotechnological potential. This study aimed to investigate the effect of SPS isolated from the seaweed Caulerpa sertularioides on adipogenic differentiation as a possible alternative treatment for obesity. The SPS-rich extract from the seaweed C. sertularioides was fractioned into three SPS-rich fractions (F0.5; F0.9; and F1.8) chemically characterized. Among these four samples, only F0.9 showed a significant inhibitory effect on adipogenesis of 3T3-L1 preadipocytes. Ten SPS-rich fractions were isolated from F0.9 through ion-exchange chromatography. However, only the fraction (CS0.2) containing a sulfated glucan was able to inhibit adipogenesis. CS0.2 reduces lipid accumulation and inhibits the expression of key adipogenic (PPARγ, C/EBPβ, and C/EBPα) and lipogenic markers (SREBP-1c, Fabp4, and CD36). The data points to the potential of sulfated glucan from C. sertularioides for the development of functional approaches in obesity management.

Ecklonia maxima is a brown seaweed, which is abundantly distributed in South Africa. This study investigated an efficient approach using high-performance centrifugal partition chromatography (HPCPC), which has been successfully developed for the isolation and purification of phlorotannins, eckmaxol, and dieckol from the ethyl acetate fraction of E. maxima (EEM). We evaluated EEM for its inhibitory effect against lipopolysaccharide (LPS)-induced inflammatory responses in zebrafish embryos. The separation of eckmaxol and dieckol from samples of EEM using HPCPC was found to be of high purity and yield under an optimal solvent system composed of n-hexane:ethyl acetate:methanol:water (2:7:3:7, v/v/v/v). To evaluate the anti-inflammatory efficacy of EEM containing active compounds, zebrafish embryos exposed to LPS were compared with and without EEM treatment for nitric oxide (NO) production, reactive oxygen species (ROS) generation, and cell death two days after fertilization. These evaluations indicate that EEM alleviated inflammation by inhibiting cell death, ROS, and NO generation induced by LPS treatment. According to these results, eckmaxol and dieckol isolated from brown seaweed E. maxima could be considered effective anti-inflammatory agents as pharmaceutical and functional food ingredients.

Various seaweed sulfated polysaccharides have been explored for antimicrobial application. This study aimed to evaluate the antibacterial activity of the native Gracilaria fisheri sulfated galactans (NSG) and depolymerized fractions against the marine pathogenic bacteria Vibrio parahaemolyticus and Vibrio harveyi. NSG was hydrolyzed in different concentrations of H2O2 to generate sulfated galactans degraded fractions (SGF). The molecular weight, structural characteristics, and physicochemical parameters of both NSG and SGF were determined. The results revealed that the high molecular weight NSG (228.33 kDa) was significantly degraded to SGFs of 115.76, 3.79, and 3.19 kDa by hydrolysis with 0.4, 2, and 10% H2O2, respectively. The Fourier transformed spectroscopy (FTIR) and 1H- and 13C-Nuclear magnetic resonance (NMR) analyses demonstrated that the polysaccharide chain structure of SGFs was not affected by H2O2 degradation, but alterations were detected at the peak positions of some functional groups. In vitro study showed that SGFs significantly exerted a stronger antibacterial activity against V. parahaemolyticus and V. harveyi than NSG, which might be due to the low molecular weight and higher sulfation properties of SGF. SGF disrupted the bacterial cell membrane, resulting in leakage of intracellular biological components, and subsequently, cell death. Taken together, this study provides a basis for the exploitation and utilization of low-molecular-weight sulfated galactans from G. fisheri to prevent and control the shrimp pathogens.

Prostate cancer (PCa) is the leading cause of cancer death in men, and its treatment is commonly associated with severe adverse effects. Thus, new treatment modalities are required. In this context, natural compounds have been widely explored for their anti-PCa properties. Aquatic organisms contain numerous potential medications. Anticancer peptides are less toxic to normal cells and provide an efficacious treatment approach via multiple mechanisms, including altered cell viability, apoptosis, cell migration/invasion, suppression of angiogenesis and microtubule balance disturbances. This review sheds light on marine peptides as efficacious and safe therapeutic agents for PCa.

Aging has become a global public health challenge. Many studies have revealed that the excessive generation of ROS and oxidative stress could be the major causative factors contributing to aging. In this study, R-phycocyanin (R-PC) was isolated from Porphyra haitanensis, and its anti-aging ability was explored by natural aging Drosophila melanogaster and H2O2-induced HUVEC cells as the aging model. Results showed that R-PC α and β subunits expressed have antioxidant activity and can inhibit the generation of radicals, exhibiting a protective effect against H2O2-induced apoptotic HUVEC cells death. R-PC prevented the H2O2-induced HUVEC cell cycle phase arrest by regulating cell cycle-related protein. Furthermore, R-PC prevented the H2O2-induced HUVEC cell cycle phase arrest by regulating cell-cycle-related protein expression. In vivo study also indicated that R-PC significantly increased the survival time and alleviated the oxidative stress of Drosophila melanogaster. Moreover, R-PC notably decreased levels of ROS in natural aging flies and inhibited lipid peroxidation by enhancing the expressions of the endogenous stress marker genes (SOD1, SOD2, CAT of Drosophila melanogaster). Taken together, a study on the antioxidation extract from Porphyra haitanensis, such as R-PC, may open a new window for the prevention of anti-aging.

Erectile dysfunction (ED) is the inability to achieve and/or maintain a penile erection sufficient for sexual satisfaction. Currently, many patients do not respond to the pharmacotherapy. The effects of a supplementation with Spirulina platensis, were evaluated in a model of ED induced by hypercaloric diet consumption. Wistar rats were divided into groups fed with standard diet (SD) or hypercaloric diet (HD) and supplemented with this alga at doses of 25, 50 or 100 mg/kg. Experimental adiposity parameters and erectile function were analyzed. In SD groups, Spirulina platensis reduced food intake, final body mass and adiposity index, and increased the total antioxidant capacity (TAC) of adipose tissue. However, no change was observed in erectile function. In the HD group, without Spirulina supplementation, a decrease in food intake was observed, in addition to an increase of final body mass, weight gain, adipose reserves, and adiposity index. Additionally, reduction in the number and increase in the latency of penile erection and adipose malondialdehyde levels, as well as a reduction in TCA was noted. Furthermore, cavernous contractility was increased, and the relaxing response was decreased. Interestingly, these deleterious effects were prevented by the algae at doses of 25, 50 and/or 100 mg/kg. Therefore, the supplementation with S. platensis prevents damages associated to a hypercaloric diet consumption and emerges as an adjuvant the prevention of ED.

The TRPA1 channel is involved in a variety of physiological processes and its activation leads to pain perception and the development of inflammation. Peptide Ms 9a-1 from sea anemone Metridium senile is a positive modulator of TRPA1 and causes significant analgesic and anti-inflammatory effects by desensitization of TRPA1-expressing sensory neurons. For structural and functional analysis of Ms 9a-1, we produced four peptides-Ms 9a-1 without C-terminal domain (abbreviated as N-Ms), short C-terminal domain Ms 9a-1 alone (C-Ms), and two homologous peptides (Ms 9a-2 and Ms 9a-3). All tested peptides possessed a reduced potentiating effect on TRPA1 compared to Ms 9a-1 in vitro. None of the peptides reproduced analgesic and anti-inflammatory properties of Ms 9a-1 in vivo. Peptides N-Ms and C-Ms were able to reduce pain induced by AITC (selective TRPA1 agonist) but did not decrease AITC-induced paw edema development. Fragments of Ms 9a-1 did not effectively reverse CFA-induced thermal hyperalgesia and paw edema. Ms 9a-2 and Ms 9a-3 possessed significant effects and anti-inflammatory properties in some doses, but their unexpected efficacy and bell-shape dose-responses support the hypothesis of other targets involved in their effects in vivo. Therefore, activity comparison of Ms 9a-1 fragments and homologues peptides revealed structural determinants important for TRPA1 modulation, as well as analgesic and anti-inflammatory properties of Ms9a-1.

Three new glycosylated secondary metabolites, including a new indole alkaloid, pityriacitrin D (1), and two new trehalose lipids (2 and 3), together with three known compounds (4-6) were isolated from two marine-derived bacterial strains, Bacillus siamensis 168CLC-66.1 and Tsukamurella pseudospumae IV19-045. The structures of 1-3 were determined by extensive analysis and comparison of their spectroscopic data with literature values. The absolute configurations of sugar moieties were determined by chemical derivatization followed by LC-MS analysis. Cytotoxicity of 1-3 against six cancer cell lines was evaluated by SRB assay, and 1 showed moderate activity against all the tested cell lines with GI50 values ranging from 8.0 to 10.9 µM.

The discovery of novel secondary metabolites is actively being pursued in new ecosystems. Sponge-associated bacteria have been in the limelight in recent years on account of their ability to produce bioactive compounds. In this study, heterotrophic bacteria associated with four sponge species were isolated, taxonomically identified, and subjected to screening for the production of bioactive entities against a panel of nine microorganisms, including Gram-positive and negative bacteria, as well as yeast and fungi. Of the 105 isolated strains, 66% were represented by Proteobacteria, 16% by Bacteriodetes, 7% by Actinobacteria, and 11% by Firmicutes. Bioactivity screening revealed that 40% of the total isolated strains showed antimicrobial activity against one or more of the target microorganisms tested. Further, active extracts from selective species were narrowed down by bioassay-guided fractionation and subsequently identified by HR-ESI-MS analyses to locate the active peaks. Presumably responsible compounds for the observed bioactivities were identified as pentadecenoic acid, oleic acid, and palmitoleic acid. One isolate, Qipengyuania pacifica NZ-96T, based on 16S rRNA novelty, was subjected to comparative metabolic reconstruction analysis with its closest phylogenetic neighbors, revealing 79 unique functional roles in the novel isolate. In addition, genome mining of Qipengyuania pacifica NZ-96T revealed three biosynthetic gene clusters responsible for the biosynthesis of terpene, beta lactone, lasso peptide, and hserlactone secondary metabolites. Our results demonstrate the ability to target the sponge microbiome as a potential source of novel microbial life with biotechnological potential.

Agar is widely applied across the food, pharmaceutical and biotechnology industries, owing to its various bioactive functions. To better understand the agar biosynthesis in commercial seaweed Gracilariopsis lemaneiformis, the activities of four enzymes participating in the agar biosynthesis were detected, and phosphoglucomutase (PGM) was confirmed as highly correlated with agar accumulation. Three genes of PGM (GlPGM1, GlPGM2 and GlPGM3) were identified from the G. lemaneiformis genome. The subcellular localization analysis validated that GlPGM1 was located in the chloroplast and GlPGM3 was not significantly distributed in the organelles. Both the GlPGM1 and GlPGM3 protein levels showed a remarkable consistency with the agar variations, and GlPGM3 may participate in the carbon flux between (iso)floridoside, floridean starch and agar synthesis. After treatment with the PGM inhibitor, the agar and floridean starch contents and the activities of floridean starch synthase were significantly decreased; products identified in the Calvin cycle, the pentose phosphate pathway, the Embden-Meyerhof-Parnas pathway and the tricarboxylic acid cycle were depressed; however, lipids, phenolic acids and the intermediate metabolites, fructose-1,6-phosphate were upregulated. These findings reveal the essential role of PGM in regulating the carbon flux between agar and other carbohydrates in G. lemaneiformis, providing a guide for the artificial regulation of agar accumulation.

The seaweed Sargassum muticum, collected on the southern coast of Galicia, yielded a tetraprenyltoluquinol chromane meroditerpene compound known as 1b, whose structure is revised. The relative configuration of 1b was determined by J-based configurational methodology combined with an iJ/DP4 statistical analysis and further confirmed by measuring two anisotropic properties: carbon residual chemical shift anisotropies (13C-RCSAs) and one-bond 1H-13C residual dipolar couplings (1DCH-RDCs). The absolute configuration of 1b was deduced by ECD/OR/TD-DFT methods and established as 3R,7S,11R.

Blooms of the benthic toxic dinoflagellate genus Ostreopsis have been recorded more frequently during the last two decades, particularly in warm temperate areas such as the Mediterranean Sea. The proliferation of Ostreopsis species may cause deleterious effects on ecosystems and can impact human health through skin contact or aerosol inhalation. In the eastern Atlantic Ocean, the toxic O. cf. ovata has not yet been reported to the north of Portugal, and the only species present further north was O. cf. siamensis, for which the toxic risk is considered low. During summer blooms of unidentified Ostreopsis species on the French Basque coast (Atlantic) in 2020 and 2021, people suffered from irritations and respiratory disorders, and the number of analyzed cases reached 674 in 2021. In order to investigate the causes, sampling was carried out during summer 2021 to (i) taxonomically identify Ostreopsis species present using a molecular approach, (ii) isolate strains from the bloom and culture them, and (iii) characterize the presence of known toxins which may be involved. For the first time, this study reports the presence of both O. cf. siamensis and O. cf. ovata, for which the French Basque coast is a new upper distribution limit. Furthermore, the presence of ovatoxins a, b, c, and d in the environmental sample and in a cultivated strain in culture confirmed the toxic nature of the bloom and allowed identifying O. cf. ovata as the producer. The present data identify a new health risk in the area and highlight the extended distribution of some harmful dinoflagellates, presumably in relation to climate change.

Chitin and its derivative chitosan are highly abundant polymers in nature, appearing in both the shells and exoskeletons of various marine and non-marine species. Since they possess favorable properties, such as biocompatibility, biodegradability, non-toxicity, and non-immunogenicity, they have gained recent attention due to their enormous potential biomedical applications. The polycationic surface of chitosan enables it to form hydrogenic and ionic bonds with drug molecules, which is one of its most useful properties. Because chitosan is biocompatible, it can therefore be used in drug delivery systems. The development of chitosan-based nanoparticles has also contributed to the significance of chitin as a drug delivery system that can deliver drugs topically. Furthermore, chitin can be used in cancer treatment as a vehicle for delivering cancer drugs to a specific site and has an antiproliferative effect by reducing the viability of cells. Finally, chitosan can be used as a wound dressing in order to promote the faster regeneration of skin epithelial cells and collagen production by fibroblasts. As discussed in this review, chitin and chitosan have diverse applications in the medical field. Recognizing the biomedical applications of these two polymers is essential for future research in tissue engineering and nanobiotechnology.

Hemocyanins present in the hemolymph of invertebrates are multifunctional proteins that are responsible for oxygen transport and play crucial roles in the immune system. They have also been identified as a source of antimicrobial peptides during infection in mollusks. Hemocyanin has also been identified in the cephalopod ancestor Nautilus, but antimicrobial peptides derived from the hemocyanin of Nautilus pompilius have not been reported. Here, the bactericidal activity of six predicted peptides from N. pompilius hemocyanin and seven mutant peptides was analyzed. Among those peptides, a mutant peptide with 15 amino acids (1RVFAGFLRHGIKRSR15), NpHM4, showed relatively high antibacterial activity. NpHM4 was determined to have typical antimicrobial peptide characteristics, including a positive charge (+5.25) and a high hydrophobic residue ratio (40%), and it was predicted to form an alpha-helical structure. In addition, NpHM4 exhibited significant antibacterial activity against Gram-negative bacteria (MBC = 30 μM for Vibrio alginolyticus), with no cytotoxicity to mammalian cells even at a high concentration of 180 µM. Upon contact with V. alginolyticus cells, we confirmed that the bactericidal activity of NpHM4 was coupled with membrane permeabilization, which was further confirmed via ultrastructural images using a scanning electron microscope. Therefore, our study provides a rationalization for the development and optimization of antimicrobial peptide from the cephalopod ancestor Nautilus, paving the way for future novel AMP development with broad applications.

Codium bernabei is a green alga that grows on Chilean coasts. The composition of its structural polysaccharides is still unknown. Hence, the aim of this work is to isolate and characterize the hot water extracted polysaccharide fractions. For this purpose, the water extracts were further precipitated in alcohol (TPs) and acid media (APs), respectively. Both fractions were characterized using different physicochemical techniques such as GC-MS, GPC, FTIR, TGA, and SEM. It is confirmed that the extracted fractions are mainly made of sulfated galactan unit, with a degree of sulfation of 19.3% (TPs) and 17.4% (ATs) and a protein content of 3.5% in APs and 15.6% in TPs. Other neutral sugars such as xylose, glucose, galactose, fucose, mannose, and arabinose were found in a molar ratio (0.05:0.6:1.0:0.02:0.14:0.11) for TPs and (0.05:0.31:1.0:0.03:0.1:0.13) for ATs. The molecular weight of the polysaccharide samples was lower than 20 kDa. Both polysaccharides were thermally stable (Tonset > 190 °C) and showed antioxidant activity according to the ABTS•+ and DPPH tests, where TPs fractions had higher scavenging activity (35%) compared to the APs fractions. The PT and APTTS assays were used to measure the anticoagulant activity of the polysaccharide fractions. In general, the PT activity of the TPs and APs was not different from normal plasma values. The exception was the TPs treatment at 1000 µg mL-1 concentration. The APTTS test revealed that clotting time for both polysaccharides was prolonged regarding normal values at 1000 µg mL-1. Finally, the antitumor test in colorectal carcinoma (HTC-116) cell line, breast cancer (MCF-7) and human leukemia (HL-60) cell lines showed the cytotoxic effect of TPs and APs. Those results suggest the potential biotechnological application of sulfate galactan polysaccharides isolated from a Chilean marine resource.

Posidonia oceanica (L.) Delile is an endemic Mediterranean marine plant of extreme ecological importance. Previous in vitro and in vivo studies have demonstrated the potential antidiabetic properties of P. oceanica leaf extract. Intestinal glucose transporters play a key role in glucose homeostasis and represent novel targets for the management of diabetes. In this study, the ability of a hydroalcoholic P. oceanica leaf extract (POE) to modulate intestinal glucose transporters was investigated using Caco-2 cells as a model of an intestinal barrier. The incubation of cells with POE significantly decreased glucose uptake by decreasing the GLUT2 glucose transporter levels. Moreover, POE had a positive effect on the barrier integrity by increasing the Zonulin-1 levels. A protective effect exerted by POE against oxidative stress induced by chronic exposure to high glucose concentrations or tert-butyl hydroperoxide was also demonstrated. This study highlights for the first time the effect of POE on glucose transport, intestinal barrier integrity, and its protective antioxidant effect in Caco-2 cells. These findings suggest that the P. oceanica phytocomplex may have a positive impact by preventing the intestinal cell dysfunction involved in the development of inflammation-related disease associated with oxidative stress.

Nitzschia laevis is a candidate microorganism for bioactive compounds (fucoxanthin and eicosapentaenoic acid (EPA)) production. In this study, the impacts of glucose-induced trophic transition on biomass, photosynthesis, pigments, and lipid profiles were examined. The specific growth rate was increased under glucose addition, achieved at 0.47 day-1 (0.26 ± 0.01 day-1 for the group without glucose in medium). However, the photosynthetic parameters and pigments including chlorophylls, fucoxanthin, and diatoxanthin were reduced. The net yield of EPA doubled under glucose addition, reaching 20.36 ± 1.22 mg/L in 4 days. In addition, the alteration in detailed lipid molecular species was demonstrated with a focus on EPA-enriched lipids. The effects of 2-deoxyglucose (2DG) indicated that glucose phosphorylation was involved in glucose-induced regulation. These findings provide novel data for guiding the application of this diatom strain in the functional food industries.

Identifying compounds responsible for the observed toxicity of the Gambierdiscus species is a critical step to ascertaining whether they contribute to ciguatera poisoning. Macroalgae samples were collected during research expeditions to Rarotonga (Cook Islands) and North Meyer Island (Kermadec Islands), from which two new Gambierdiscus species were characterized, G. cheloniae CAWD232 and G. honu CAWD242. Previous chemical and toxicological investigations of these species demonstrated that they did not produce the routinely monitored Pacific ciguatoxins nor maitotoxin-1 (MTX-1), yet were highly toxic to mice via intraperitoneal (i.p.) injection. Bioassay-guided fractionation of methanolic extracts, incorporating wet chemistry and chromatographic techniques, was used to isolate two new MTX analogs; MTX-6 from G. cheloniae CAWD232 and MTX-7 from G. honu CAWD242. Structural characterization of the new MTX analogs used a combination of analytical chemistry techniques, including LC-MS, LC-MS/MS, HR-MS, oxidative cleavage and reduction, and NMR spectroscopy. A substantial portion of the MTX-7 structure was elucidated, and (to a lesser extent) that of MTX-6. Key differences from MTX-1 included monosulfation, additional hydroxyl groups, an extra double bond, and in the case of MTX-7, an additional methyl group. To date, this is the most extensive structural characterization performed on an MTX analog since the complete structure of MTX-1 was published in 1993. MTX-7 was extremely toxic to mice via i.p. injection (LD50 of 0.235 µg/kg), although no toxicity was observed at the highest dose rate via oral administration (155.8 µg/kg). Future research is required to investigate the bioaccumulation and likely biotransformation of the MTX analogs in the marine food web.

Cinnamoyl-containing nonribosomal peptides (CCNPs) form a unique family of actinobacterial secondary metabolites and display various biological activities. A new CCNP named epoxinnamide (1) was discovered from intertidal mudflat-derived Streptomyces sp. OID44. The structure of 1 was determined by the analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) data along with a mass spectrum. The absolute configuration of 1 was assigned by the combination of advanced Marfey's method, 3JHH and rotating-frame overhauser effect spectroscopy (ROESY) analysis, DP4 calculation, and genomic analysis. The putative biosynthetic pathway of epoxinnamide (1) was identified through the whole-genome sequencing of Streptomyces sp. OID44. In particular, the thioesterase domain in the nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster was proposed as a bifunctional enzyme, which catalyzes both epimerization and macrocyclization. Epoxinnamide (1) induced quinone reductase (QR) activity in murine Hepa-1c1c7 cells by 1.6-fold at 5 μM. It also exhibited effective antiangiogenesis activity in human umbilical vein endothelial cells (IC50 = 13.4 μM).

Twelve new and four known alkaloids including five different structural scaffolds were isolated from the sponge Stylissa massa collected in the South China Sea. Compound 1 is the first identified precursor metabolite of the classic 5/7/5 tricyclic skeleton with unesterified guanidine and carboxyl groups, compounds 2-5 and 13-15 belong to the spongiacidin-type pyrrole imidazole alkaloids (PIAs). Z- and E-configurations of the spongiacidin-type PIAs often appeared concomitantly and were distinguished by the chemical shift analysis of 13C NMR spectra. The structures of all twelve new compounds were determined by NMR, MS, and ECD analysis combined with single-crystal data of compounds 1, 5, and 10. In the aldose reductase (ALR2) inhibitory assay, six 5/7/5 tricyclic compounds (2-5, 13-15) displayed significant activities. Compounds 13 and 14, as the representative members of spongiacidin-PIAs, demonstrated their ALR2-targeted activities in SPR experiments with KD values of 12.5 and 6.9 µM, respectively.

The role of NLRP3 in the tumour microenvironment is elusive. In some cancers, the activation of NLRP3 causes a worse prognosis and in some cancers, NLRP3 increases chances of survivability. However, in many cases where NLRP3 has a protumorigenic role, inhibition of NLRP3 would be a crucial step in therapy. Consequently, activation of NLRP3 would be of essence when inflammation is required. Although many ways of inhibiting and activating NLRP3 in cancers have been discussed before, not a lot of focus has been given to chitin and chitosan in this context. The availability of these marine compounds and their versatility in dealing with inflammation needs to be investigated further in relation with cancers, along with other natural extracts. In this review, the effects of NLRP3 on gastrointestinal and gynaecological cancers and the impact of different natural extracts on NLRP3s with special emphasis on chitin and chitosan is discussed. A research gap in using chitin derivatives as anti/pro-inflammatory agents in cancer treatment has been highlighted.

Investigation of the cytotoxic fractions of the ethyl acetate extract of the fermentation broth of the tunicate-derived Aspergillus sp. DY001 afforded two new dipeptides, asperopiperazines A and B (1 and 2), along with the previously reported compounds (+)-citreoisocoumarin (3) and (-)-6,8-di-O-methylcitreoisocoumarin (4). Analyses of the 1D and 2D NMR spectroscopic data of the compounds supported their structural assignments. Asperopiperazine A (1) is a cyclic dipeptide of leucine and phenylalanine moieties, which are substituted with an N-methyl and an N-acetyl group, respectively. On the other hand, asperopiperazine B (2) is a cyclic dipeptide of proline and phenylalanine moieties with a hydroxyl group at C-2 of the proline part. The absolute configuration of the amino acid moieties in 1 and 2 were determined by Marfey's analyses and DFT NMR chemical shift calculations, leading to their assignment as cyclo(l-NMe-Leu-l-NAc-Phe) and cyclo(d-6-OH-Pro-l-Phe), respectively. Asperopiperazines A and B displayed higher antimicrobial effects against Escherichia coli and Staphylococcus aureus than Candida albicans. Furthermore, compounds 1-4 displayed variable growth inhibitory effects towards HCT 116 and MDA-MB-231 cells, with asperopiperazine A as the most active one towards HCT 116.

Lipid peroxidation is associated with the development of some pathologies, such as cardiovascular diseases. Reduction in oxidative stress by antioxidants, such as Arthrospira (formely Spirulina), helps improving this redox imbalance. The aim of the study was to evaluate the effect of the Arthrospira liquid extract "Spirulysat®" on oxidative markers-in particular, oxidized LDL (oxLDL)/total LDL cholesterol-and isoprostanes and to investigate its impact on lipid and glucose metabolism in the metabolic syndrome subject. A controlled, randomised, double-blind design was conducted in 40 subjects aged 18 to 65 years with metabolic syndrome after a daily intake of Spirulysat® or placebo for twelve weeks. Blood and urinary samples were collected at three visits (V1, V2, V3) in the two groups for parameters determination. Although the Spirulysat® group showed a decrease at all visits of the oxLDL/total cholesterol ratio, there was no significant difference compared to the placebo (p = 0.36). The urinary isoprostanes concentration in the Spirulysat® group was reduced (p = 0.014) at V3. Plasma triglycerides decreased at V3 (p = 0.003) and HDL-cholesterol increased (p = 0.031) at all visits with Spirulysat®. In conclusion, Spirulysat® did not change the oxidized LDL (oxLDL)/LDL ratio but decreased the urinary isoprostanes, plasma triglycerides and increased HDL cholesterol, suggesting a beneficial effect on metabolic syndrome.