Peptides from oyster hydrolysate (OPs) have a variety of biological activities. However, its protective effect and exact mechanism on testicular injury remain poorly understood. This study aimed to evaluate the protective effect of OPs on triptolide (TP)-induced testis damage and spermatogenesis dysfunction and investigate its underlying mechanism. In this work, the TP-induced testis injury model was created while OPs were gavaged in mice for 4 weeks. The results showed that OPs significantly improved the sperm count and motility of mice, and alleviated the seminiferous tubule injury. Further study showed that OPs decreased malonaldehyde (MDA) level and increased antioxidant enzyme (SOD and GPH-Px) activities, attenuating oxidative stress and thereby reducing the number of apoptotic cells in the testis. In addition, OPs improved the activities of enzymes (LDH, ALP and ACP) related to energy metabolism in the testis and restored the serum hormone level of mice to normal. Furthermore, OPs promoted the expression of Nrf2 protein, and then increased the expression of antioxidant enzyme regulatory protein (HO-1 and NQO1) in the testis. OPs inhibited JNK phosphorylation and Bcl-2/Bax-mediated apoptosis. In conclusion, OPs have a protective effect on testicular injury and spermatogenesis disorders caused by TP, suggesting the potential protection of OPs on male reproduction.

Schizochytrium species are one of the best oleaginous thraustochytrids for high-yield production of docosahexaenoic acid (DHA, 22:6). However, the DHA yields from most wild-type (WT) strains of Schizochytrium are unsatisfactory for large-scale production. In this study, we applied the atmospheric and room-temperature plasma (ARTP) tool to obtain the mutant library of a previously isolated strain of Schizochytrium (i.e., PKU#Mn4). Two rounds of ARTP mutagenesis coupled with the acetyl-CoA carboxylase (ACCase) inhibitor (clethodim)-based screening yielded the mutant A78 that not only displayed better growth, glucose uptake and ACCase activity, but also increased (54.1%) DHA content than that of the WT strain. Subsequent optimization of medium components and supplementation improved the DHA content by 75.5 and 37.2%, respectively, compared with that of mutant A78 cultivated in the unoptimized medium. Interestingly, the ACCase activity of mutant A78 in a medium supplemented with biotin, citric acid or sodium citrate was significantly greater than that in a medium without supplementation. This study provides an effective bioengineering approach for improving the DHA accumulation in oleaginous microbes.

Collagen filaments derived from the two marine demosponges Ircinia oros and Sarcotragus foetidus were for the first time isolated, biochemically characterised and tested for their potential use in regenerative medicine. SDS-PAGE of isolated filaments revealed a main collagen subunit band of 130 kDa in both of the samples under study. DSC analysis on 2D membranes produced with collagenous sponge filaments showed higher thermal stability than commercial mammalian-derived collagen membranes. Dynamic mechanical and thermal analysis attested that the membranes obtained from filaments of S. foetidus were more resistant and stable at the rising temperature, compared to the ones derived from filaments of I. oros. Moreover, the former has higher stability in saline and in collagenase solutions and evident antioxidant activity. Conversely, their water binding capacity results were lower than that of membranes obtained from I. oros. Adhesion and proliferation tests using L929 fibroblasts and HaCaT keratinocytes resulted in a remarkable biocompatibility of both developed membrane models, and gene expression analysis showed an evident up-regulation of ECM-related genes. Finally, membranes from I. oros significantly increased type I collagen gene expression and its release in the culture medium. The findings here reported strongly suggest the biotechnological potential of these collagenous structures of poriferan origin as scaffolds for wound healing.

Voltage-gated sodium channels (VGSCs) are considered to be one of the most important ion channels given their remarkable physiological role. VGSCs constitute a family of large transmembrane proteins that allow transmission, generation, and propagation of action potentials. This occurs by conducting Na+ ions through the membrane, supporting cell excitability and communication signals in various systems. As a result, a wide range of coordination and physiological functions, from locomotion to cognition, can be accomplished. Drugs that target and alter the molecular mechanism of VGSCs' function have highly contributed to the discovery and perception of the function and the structure of this channel. Among those drugs are various marine toxins produced by harmful microorganisms or venomous animals. These toxins have played a key role in understanding the mode of action of VGSCs and in mapping their various allosteric binding sites. Furthermore, marine toxins appear to be an emerging source of therapeutic tools that can relieve pain or treat VGSC-related human channelopathies. Several studies documented the effect of marine toxins on VGSCs as well as their pharmaceutical applications, but none of them underlined the principal marine toxins and their effect on VGSCs. Therefore, this review aims to highlight the neurotoxins produced by marine animals such as pufferfish, shellfish, sea anemone, and cone snail that are active on VGSCs and discuss their pharmaceutical values.

Brown algae (Phaeophyceae) have been consumed by humans for hundreds of years. Current studies have shown that brown algae are rich sources of bioactive compounds with excellent nutritional value, and are considered functional foods with health benefits. Polysaccharides are the main constituents of brown algae; their diverse structures allow many unique physical and chemical properties that help to moderate a wide range of biological activities, including immunomodulation, antibacterial, antioxidant, prebiotic, antihypertensive, antidiabetic, antitumor, and anticoagulant activities. In this review, we focus on the major polysaccharide components in brown algae: the alginate, laminarin, and fucoidan. We explore how their structure leads to their health benefits, and their application prospects in functional foods and pharmaceuticals. Finally, we summarize the latest developments in applied research on brown algae polysaccharides.

Marine invertebrates represent a vast, untapped source of bioactive compounds. Cnidarians are represented by nearly 10,000 species that contain a complex mixture of venoms, collagen, and other bioactive compounds, including enzymes, oligosaccharides, fatty acids, and lipophilic molecules. Due to their high abundance in coastal waters, several jellyfish taxa may be regarded as candidate targets for the discovery of novel lead molecules and biomaterials and as a potential source of food/feed ingredients. The moon jellyfish Aurelia coerulea is one of the most common jellyfish worldwide and is particularly abundant in sheltered coastal lagoons and marinas of the Mediterranean Sea, where it first appeared-as an alien species-in the last century, when Pacific oyster cultivation began. In the present study, the antioxidant and lysozyme antibacterial activities associated with extracts from different medusa compartments-namely the umbrella, oral arms, and secreted mucus-were investigated. Extracts from the oral arms of A. coerulea displayed significant antioxidant activity. Similarly, lysozyme-like activity was the highest in extracts from oral arms. These findings suggest that A. coerulea outbreaks may be used in the search for novel cytolytic and cytotoxic products against marine bacteria. The geographically wide occurrence and the seasonally high abundance of A. coerulea populations in coastal waters envisage and stimulate the search for biotechnological applications of jellyfish biomasses in the pharmaceutical, nutritional, and nutraceutical sectors.

Four new chlorinated meroterpenoids, merochlorins G-J (1-4), and 10, a dihydronaphthalenedione precursor, along with known merochlorins A (5) and C-F (6-9), were obtained from cultivation of the bacterium strain Streptomyces sp. CNH-189, which was isolated from marine sediment. The planar structures of compounds 1-4 and 10 were elucidated by interpretation of MS, UV, and NMR spectroscopic data. The relative configurations of compounds 1-4 were determined via analysis of nuclear Overhauser effect (NOE) spectroscopic data, after which their absolute configurations were established by comparing the experimental electronic circular dichroism (ECD) spectra of compounds 1-4 to those of previously reported possible enantiomer models and DP4 calculations. Compound 3 displayed strong antibacterial activities against Bacillus subtilis, Kocuria rhizophila, and Staphylococcus aureus, with MIC values of 1, 2, and 2 μg/mL, respectively, whereas compound 1 exhibited weak antibacterial effects on these three strains, with a 16-32 μg/mL MIC value range.

Green extraction was applied to Argentinean shortfin squid (Illex argentinus) viscera, consisting of a wet pressing method including a drying step, mechanic pressing, centrifugation of the resulting slurry, and oil collection. To maximise the oil yield and ω3 fatty acid content and to minimise the oil damage degree, a response surface methodology (RSM) design was developed focused on the drying temperature (45-85 °C) and time (30-90 min). In general, an increase of the drying time and temperature provided an increase in the lipid yield recovery from the viscera. The strongest drying conditions showed a higher recovery than 50% when compared with the traditional chemical method. The docosahexaenoic and eicosapentaenoic acid contents in the extracted oil revealed scarce dependence on drying conditions, showing valuable ranges (149.2-166.5 and 88.7-102.4 g·kg-1 oil, respectively). Furthermore, the values of free fatty acids, peroxides, conjugated dienes, and ω3/ω6 ratio did not show extensive differences by comparing oils obtained from the different drying conditions. Contrary, a polyene index (PI) decrease was detected with increasing drying time and temperature. The RSM analysis indicated that optimised drying time (41.3 min) and temperature (85 °C) conditions would lead to 74.73 g·kg-1 (oil yield), 1.87 (PI), and 6.72 (peroxide value) scores, with a 0.67 desirability value.

Optimizing the alkali treatment process alone without tracking the changes of algae and agar quality with each pretreatment process will not achieve the optimal agar yield and final quality. In this study, we monitored the changes of the morphology and weight of algae with each treatment process, and comprehensively analyzed the effects of each pretreatment process on the quality of agar by combining the changes of the physicochemical properties of agar. In conventional alkali-extraction technology, alkali treatment (7%, w/v) alone significantly reduced the weight of algae (52%), but hindered the dissolution of algae, resulting in a lower yield (4%). Acidification could solve the problem of algal hardening after alkali treatment to improve the yield (12%). In enzymatic extraction technology, agar with high purity cannot be obtained by enzyme treatment alone, but low gel strength (405 g/cm2) and high sulfate content (3.4%) can be obtained by subsequent acidification and bleaching. In enzyme-assisted extraction technology, enzyme damage to the surface fiber of algae promoted the penetration of low-concentration alkali (3%, w/v), which ensured a high desulfurization efficiency and a low gel degradation rate, thus improving yield (24.7%) and gel strength (706 g/cm2), which has the potential to replace the traditional alkali-extraction technology.

Marine macroalgae is known to be a good source of mycosporine-like amino acids (MAAs), especially red macroalgae. As a new type of active substance with commercial development prospects, the current progress in the extraction, isolation and characterization of MAAs is far from sufficient in terms of effectiveness in application. To determine the extraction processes of MAAs from four species of red macroalgae (Bangia fusco-purpurea, Gelidium amansii, Gracilaria confervoides, and Gracilaria sp.), a series of single-factor and orthogonal experiments were carried out in which the effects of solvents, the solid-liquid ratio, the time of extraction, the extraction degree and the temperature, on the yields of MAA extracts, were analyzed. Further, the isolation and identification of MAAs from Bangia fusco-purpurea and Gracilaria sp. were investigated. The results showed that the solid-liquid ratio, the time of extraction, the extraction degree and the temperature were 1:20 g/mL, 2 h, three times and 40 °C, respectively, when 25% methanol or 25% ethanol were used as the extraction solvent; these values were found to be suitable for the extraction of MAAs from four species of red macroalgae. Silica gel thin-layer chromatography was successfully used, for the first time, for the detection MAAs in this work, and it could be clearly seen that Bangia fusco-purpurea had the highest contents of MAAs among the four species of red macroalgae. MAA extracts from Bangia fusco-purpurea (or Gracilaria sp.) were isolated by silica gel column chromatography to obtain one fraction (or two fractions). The compositions and proportions of the MAAs in these fractions were determined via HPLC-ESI-MS spectra and by comparison with existing studies. Shinorine, palythine and porphyra-334 were found in 95.4% of the T1 fraction, and palythenic acid was found in 4.6% of this fraction, while shinorine, palythine and porphyra-334 were found in 96.3% of the J1 fraction, palythenic acid was found in 3.7% of the J2 fraction, and palythine was found in 100% of the J2 fraction, taken from the MAA extracts found in Bangia fusco-purpurea and Gracilaria sp., respectively. In addition, the relevant compositions and proportions of the MAA extracts taken from Gelidium amansii and Gracilaria confervoides were identified. This was the first study to report on the extraction process, isolation and identification of MAAs from Bangia fusco-purpurea, Gelidium amansii, Gracilaria confervoides, and Gracilaria sp.

Models created by the intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-GalN) have been widely used to study the pathogenesis of human acute liver failure (ALF) and drug development. Our previous study reported that oyster (Crassostrea gigas) hydrolysate (OH) had a hepatoprotective effect in LPS/D-GalN-injected mice. This study was performed to identify the hepatoprotective effect of the tyrosine-alanine (YA) peptide, the main component of OH, in a LPS/D-GalN-injected ALF mice model. We analyzed the effect of YA on previously known mechanisms of hepatocellular injury in the model. LPS/D-GalN-injected mice showed inflammatory, apoptotic, ferroptotic, and pyroptotic liver injury. The pre-administration of YA (10 mg/kg or 50 mg/kg) significantly reduced the liver damage factors. The hepatoprotective effect of YA was higher in the 50 mg/kg YA pre-administered group than in the 10 mg/kg YA pre-administered group. These results showed that YA had a hepatoprotective effect by reducing inflammation, apoptosis, ferroptosis, and pyroptosis in the LPS/D-GalN-injected ALF mouse model. We suggest that YA can be used as a functional peptide for the prevention of acute liver injury.

An ubiquinone derivative, pseudoalteromone A (1), has been isolated from two marine-derived Pseudoalteromonas spp., APmarine002 and ROA-050, and its anti-melanogenesis activity was investigated. The anti-melanogenic capacity of pseudoalteromone A was demonstrated by assessing the intracellular and extracellular melanin content and cellular tyrosinase activity in the B16 cell line, Melan-a mouse melanocyte cell line, and MNT-1 human malignant melanoma cell line. Treatment with pseudoalteromone A (40 μg/mL) for 72 h reduced α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin production by up to 44.68% in B16 cells and 38.24% in MNT-1 cells. Notably, pseudoalteromone A induced a concentration-dependent reduction in cellular tyrosinase activity in B16 cell, and Western blot analyses showed that this inhibitory activity was associated with a significant decrease in protein levels of tyrosinase and tyrosinase-related protein 1 (Tyrp-1), suggesting that pseudoalteromone A exerts its anti-melanogenesis activity through effects on melanogenic genes. We further evaluated the skin-whitening effect of pseudoalteromone A in the three-dimensional (3D) pigmented-epidermis model, MelanoDerm, and visualized the 3D distribution of melanin by two-photon excited fluorescence imaging in this human skin equivalent. Collectively, our findings suggest that pseudoalteromone A inhibits tyrosinase activity and expression and that this accounts for its anti-melanogenic effects in melanocytes.

Four new indole-diterpenoids, named penerpenes K-N (1-4), along with twelve known ones (5-16), were isolated from the fermentation broth produced by adding L-tryptophan to the culture medium of the marine-derived fungus Penicillium sp. KFD28. The structures of the new compounds were elucidated extensively by 1D and 2D NMR, HRESIMS data spectroscopic analyses and ECD calculations. Compound 4 represents the second example of paxilline-type indole diterpene bearing a 1,3-dioxepane ring. Three compounds (4, 9, and 15) were cytotoxic to cancer cell lines, of which compound 9 was the most active and showed cytotoxic activity against the human liver cancer cell line BeL-7402 with an IC50 value of 5.3 μM. Moreover, six compounds (5, 7, 10, 12, 14, and 15) showed antibacterial activities against Staphylococcus aureus ATCC 6538 and Bacillus subtilis ATCC 6633.

Two known Polybrominated Diphenyl Ethers (PBDEs), 3,4,5-tribromo-2-(2',4'-dibromophenoxy)phenol (1d) and 3,4,5,6-tetrabromo-2-(2',4'-dibromophenoxy)phenol (2b), were isolated from the Indonesian marine sponge Lamellodysidea herbacea. The structure was confirmed using 13C chemical shift average deviation and was compared to the predicted structures and recorded chemical shifts in previous studies. We found a wide range of bioactivities from the organic crude extract, such as (1) a strong deterrence against the generalist pufferfish Canthigaster solandri, (2) potent inhibition against environmental and human pathogenic bacterial and fungal strains, and (3) the inhibition of the Hepatitis C Virus (HCV). The addition of a bromine atom into the A-ring of compound 2b resulted in higher fish feeding deterrence compared to compound 1d. On the contrary, compound 2b showed only more potent inhibition against the Gram-negative bacteria Rhodotorula glutinis (MIC 2.1 μg/mL), while compound 1d showed more powerful inhibition against the other human pathogenic bacteria and fungi. The first report of a chemical defense by compounds 1d and 2b against fish feeding and environmental relevant bacteria, especially pathogenic bacteria, might be one reason for the widespread occurrence of the shallow water sponge Lamellodysidea herbacea in Indonesia and the Indo-Pacific.

Phenazines are a large group of nitrogen-containing heterocycles, providing diverse chemical structures and various biological activities. Natural phenazines are mainly isolated from marine and terrestrial microorganisms. So far, more than 100 different natural compounds and over 6000 synthetic derivatives have been found and investigated. Many phenazines show great pharmacological activity in various fields, such as antimicrobial, antiparasitic, neuroprotective, insecticidal, anti-inflammatory and anticancer activity. Researchers continued to investigate these compounds and hope to develop them as medicines. Cimmino et al. published a significant review about anticancer activity of phenazines, containing articles from 2000 to 2011. Here, we mainly summarize articles from 2012 to 2021. According to sources of compounds, phenazines were categorized into natural phenazines and synthetic phenazine derivatives in this review. Their pharmacological activities, mechanisms of action, biosynthetic pathways and synthetic strategies were summarized. These may provide guidance for the investigation on phenazines in the future.

The common Antarctic red alga Plocamium sp. is rich in halogenated monoterpenes with known anticancer and antimicrobial properties and extracts of Plocamium sp. have strong ecological activity in deterring feeding by sympatric herbivores. Plocamium sp. collected near Anvers Island, Antarctica showed a high degree of secondary metabolite diversity between separate individuals. GC/MS results revealed 15 different combinations of metabolites (chemogroups) across individuals, which were apparent at 50% or greater Bray-Curtis similarity and also clearly distinguishable by eye when comparing chromatographic profiles of the secondary metabolomes. Sequencing of the mitochondrial cox1 gene revealed six distinct haplotypes, of which the most common two had been previously reported (now referred to as Haplotypes 1 and 2). With the exception of one individual, three of the chemogroups were only produced by individuals in Haplotype 1. All the other 12 chemogroups were produced by individuals in Haplotype 2, with five of these chemogroups also present in one of the four new, less common haplotypes that only differed from Haplotype 2 by one base pair. The functional relevance of this metabolomic and genetic diversity is unknown, but they could have important ecological and evolutionary ramifications, thus potentially providing a foundation for differential selection.

Cardiovascular disease represents a leading cause of mortality and is often characterized by the emergence of endothelial dysfunction (ED), a physiologic condition that takes place in the early progress of atherosclerosis. In this study, two cytoprotective peptides derived from blue mussel chymotrypsin hydrolysates with the sequence of EPTF and FTVN were purified and identified. Molecular mechanisms underlying the cytoprotective effects against oxidative stress which lead to human umbilical vein endothelial cells (HUVEC) injury were investigated. The results showed that pretreatment of EPTF, FTVN and their combination (1:1) in 0.1 mg/mL significantly reduced HUVEC death due to H2O2 exposure. The cytoprotective mechanism of these peptides involves an improvement in the cellular antioxidant defense system, as indicated by the suppression of the intracellular ROS generation through upregulation of the cytoprotective enzyme heme oxygenase-1. In addition, H2O2 exposure triggers HUVEC damage through the apoptosis process, as evidenced by increased cytochrome C release, Bax protein expression, and the elevated amount of activated caspase-3, however in HUVEC pretreated with peptides and their combination, the presence of those apoptotic stimuli was significantly decreased. Each peptide showed similar cytoprotective effect but no synergistic effect. Taken together, these peptides may be especially important in protecting against oxidative stress-mediated ED.

Metabolic syndrome is the pathological basis of cardiovascular and cerebrovascular diseases and type 2 diabetes. With the prevalence of modern lifestyles, the incidence of metabolic syndrome has risen rapidly. In recent years, marine sulfate polysaccharides (MSPs) have shown positive effects in the prevention and treatment of metabolic syndrome, and they mainly come from seaweeds and marine animals. MSPs are rich in sulfate and have stronger biological activity compared with terrestrial polysaccharides. MSPs can alleviate metabolic syndrome by regulating glucose metabolism and lipid metabolism. In addition, MSPs prevent and treat metabolic syndrome by interacting with gut microbiota. MSPs can be degraded by gut microbes to produce metabolites such as short chain fatty acids (SCFAs) and free sulfate and affect the composition of gut microbiota. The difference between MSPs and other polysaccharides lies in the sulfation pattern and sulfate content, therefore, which is very important for anti-metabolic syndrome activity of MSPs. This review summarizes the latest findings on effects of MSPs on metabolic syndrome, mechanisms of MSPs in treatment/prevention of metabolic syndrome, interactions between MSPs and gut microbiota, and the role of sulfate group and sulfation pattern in MSPs activity. However, more clinical trials are needed to confirm the potential preventive and therapeutic effects on human body. It may be a better choice to develop new functional foods containing MSPs for dietary intervention in metabolic syndrome.

Gnathonemuspetersii (F. Mormyridae) commonly known as Peters' elephant-nose fish is a freshwater elephant fish native to West and Central African rivers. The present research aimed at metabolic profiling of its derived crude oil via GC-MS analysis. In addition, wound healing aptitude in adult male New Zealand Dutch strain albino rabbits along with isolated bioactive compounds in comparison with a commercial product (Mebo®). The molecular mechanism was studied through a number of in vitro investigations, i.e., radical scavenging and inhibition of COX enzymes, in addition to in silico molecular docking study. The results revealed a total of 35 identified (71.11%) compounds in the fish oil, belonging to fatty acids (59.57%), sterols (6.11%), and alkanes (5.43%). Phytochemical investigation of the crude oil afforded isolation of six compounds 1-6. Moreover, the crude oil showed significant in vitro hydrogen peroxide and superoxide radical scavenging activities. Furthermore, the crude oil along with one of its major components (compound 4) exhibited selective inhibitory activity towards COX-2 with IC50 values of 15.27 and 2.41 µM, respectively. Topical application of the crude oil on excision wounds showed a significant (p < 0.05) increase in the wound healing rate in comparison to the untreated and Mebo®-treated groups, where fish oil increased the TGF-β1 expression, down-regulated TNF-α, and IL-1β. Accordingly, Peters' elephant-nose fish oil may be a potential alternative medication helping wound healing owing to its antioxidant and anti-inflammatory activities.

Fucoxanthin is a major carotenoid in brown macroalgae and diatoms that possesses a broad spectrum of health benefits. This review evaluated the research trends of the fucoxanthin field from 1928 to June 2021 using the bibliometric method. The present findings unraveled that the fucoxanthin field has grown quickly in recent years with a total of 2080 publications. Japan was the most active country in producing fucoxanthin publications. Three Japan institutes were listed in the top ten productive institutions, with Hokkaido University being the most prominent institutional contributor in publishing fucoxanthin articles. The most relevant subject area on fucoxanthin was the agricultural and biological sciences category, while most fucoxanthin articles were published in Marine Drugs. A total of four research concepts emerged based on the bibliometric keywords analysis: "bioactivities", "photosynthesis", "optimization of process'', and "environment". The "bioactivities" of fucoxanthin was identified as the priority in future research. The current analysis highlighted the importance of collaboration and suggested that global collaboration could be the key to valorizing and efficiently boosting the consumer acceptability of fucoxanthin. The present bibliometric analysis offers valuable insights into the research trends of fucoxanthin to construct a better future development of this treasurable carotenoid.

The article describes the structure-activity relationships (SAR) for a broad series of sea cucumber glycosides on different tumor cell lines and erythrocytes, and an in silico modulation of the interaction of selected glycosides from the sea cucumber Eupentacta fraudatrix with model erythrocyte membranes using full-atom molecular dynamics (MD) simulations. The in silico approach revealed that the glycosides bound to the membrane surface mainly through hydrophobic interactions and hydrogen bonds. The mode of such interactions depends on the aglycone structure, including the side chain structural peculiarities, and varies to a great extent. Two different mechanisms of glycoside/membrane interactions were discovered. The first one was realized through the pore formation (by cucumariosides A1 (40) and A8 (44)), preceded by bonding of the glycosides with membrane sphingomyelin, phospholipids, and cholesterol. Noncovalent intermolecular interactions inside multimolecular membrane complexes and their stoichiometry differed for 40 and 44. The second mechanism was realized by cucumarioside A2 (59) through the formation of phospholipid and cholesterol clusters in the outer and inner membrane leaflets, correspondingly. Noticeably, the glycoside/phospholipid interactions were more favorable compared to the glycoside/cholesterol interactions, but the glycoside possessed an agglomerating action towards the cholesterol molecules from the inner membrane leaflet. In silicosimulations of the interactions of cucumarioside A7 (45) with model membrane demonstrated only slight interactions with phospholipid polar heads and the absence of glycoside/cholesterol interactions. This fact correlated well with very low experimental hemolytic activity of this substance. The observed peculiarities of membranotropic action are in good agreement with the corresponding experimental data on hemolytic activity of the investigated compounds in vitro.

Prevalence and incidence of the marine toxins (paralytic, amnesic, and lipophilic toxins) including the so-called emerging toxins (these are, gymnodimines, pinnatoxins, or spirolides among others) have increased in recent years all over the world. Climate change, which is affecting the distribution of their producing phytoplankton species, is probably one of the main causes. Early detection of the toxins present in a particular area, and linking the toxins to their causative phytoplankton species are key tools to minimize the risk they pose for human consumers. The development of both types of studies requires fast and highly sensitive analytical methods. In the present work, we have developed a highly sensitive liquid chromatography-mass spectrometry methodology (LC-MS/MS), using a column with fused-core particle technology, for the determination of fourteen lipophilic toxins in a single run of 3.6 min. The performance of the method was evaluated for specificity, linearity, precision (repeatability and reproducibility) and accuracy by analysing spiked and naturally contaminated samples. The in-house validation was successful, and the limit of detection (LOD) and quantification (LOQ) for all the toxins were far below their regulatory action limits. The method is suitable to be considered in monitoring systems of bivalves for food control.

The disruption of pathogen communication or quorum-sensing (QS) via quorum-quenching (QQ) molecules has been proposed as a promising strategy to fight bacterial infections. Bacillus spp. have recognizable biotechnology applications, namely as probiotic health-promoting agents or as a source of natural antimicrobial molecules, including QQ molecules. This study characterized the QQ potential of 200 Bacillus spp., isolated from the gut of different aquaculture fish species, to suppress fish pathogens QS. Approximately 12% of the tested Bacillus spp. fish isolates (FI). were able to interfere with synthetic QS molecules. Ten isolates were further selected as producers of extracellular QQ-molecules and their QQ capacity was evaluated against the QS of important aquaculture bacterial pathogens, namely Aeromonas spp., Vibrio spp., Photobacterium damselae, Edwardsiela tarda, and Shigella sonnei. The results revealed that A. veronii and E. tarda produce QS molecules that are detectable by the Chr. violaceum biosensor, and which were degraded when exposed to the extracellular extracts of three FI isolates. Moreover, the same isolates, identified as B. subtilis, B. vezelensis, and B. pumilus, significantly reduced the pathogenicity of E. tarda in zebrafish larvae, increasing its survival by 50%. Taken together, these results identified three Bacillus spp. capable of extracellularly quenching aquaculture pathogen communication, and thus become a promising source of bioactive molecules for use in the biocontrol of aquaculture bacterial diseases.

Actinomycin (Act) V, an analogue of Act D, presented stronger antitumor activity and less hepatorenal toxicity than Act D in our previous studies, which is worthy of further investigation. We hereby report that Act V induces apoptosis via mitochondrial and PI3K/AKT pathways in colorectal cancer (CRC) cells. Act V-induced apoptosis was characterized by mitochondrial dysfunction, with loss of mitochondria membrane potential (MMP) and cytochrome c release, which then activated cleaved caspase-9, cleaved caspase-3, and cleaved PARP, revealing that it was related to the mitochondrial pathway, and the apoptotic trendency can be reversed by caspase inhibitor Z-VAD-FMK. Furthermore, we proved that Act V significantly inhibited PI3K/AKT signalling in HCT-116 cells using cell experiments in vitro, and it also presented a potential targeted PI3Kα inhibition using computer docking models. Further elucidation revealed that it exhibited a 28-fold greater potency than the PI3K inhibitor LY294002 on PI3K inhibition efficacy. Taken together, Act V, as a superior potential replacement of Act D, is a potential candidate for inhibiting the PI3K/AKT pathway and is worthy of more pre-clinical studies in the therapy of CRC.

With the advancement of nanotechnology, several nanoparticles have been synthesized as antimicrobial agents by utilizing biologically derived materials. In most cases, the materials used for the synthesis of nanoparticles from natural sources are extracts. Natural extracts contain a wide range of bioactive components, making it difficult to pinpoint the exact component responsible for nanoparticle synthesis. Furthermore, the bioactive component present in the extract changes according to numerous environmental factors. As a result, the current work intended to synthesize gold (AuNPs) and zinc oxide (ZnONPs) nanoparticles using pure phloroglucinol (PG). The synthesized PG-AuNPs and PG-ZnONPs were characterized using a UV-Vis absorption spectrophotometer, FTIR, DLS, FE-TEM, zeta potential, EDS, and energy-dispersive X-ray diffraction. The characterized PG-AuNPs and PG-ZnONPs have been employed to combat the pathogenesis of Pseudomonas aeruginosa. P. aeruginosa is recognized as one of the most prevalent pathogens responsible for the common cause of nosocomial infection in humans. Antimicrobial resistance in P. aeruginosa has been linked to the development of recalcitrant phenotypic characteristics, such as biofilm, which has been identified as one of the major obstacles to antimicrobial therapy. Furthermore, P. aeruginosa generates various virulence factors that are a major cause of chronic infection. These PG-AuNPs and PG-ZnONPs significantly inhibit early stage biofilm and eradicate mature biofilm. Furthermore, these NPs reduce P. aeruginosa virulence factors such as pyoverdine, pyocyanin, protease, rhamnolipid, and hemolytic capabilities. In addition, these NPs significantly reduce P. aeruginosa swarming, swimming, and twitching motility. PG-AuNPs and PG-ZnONPs can be used as control agents for infections caused by the biofilm-forming human pathogenic bacterium P. aeruginosa.

Crustins are widely distributed among different crustacean groups. They are characterized by a whey acidic protein (WAP) domain, and most examined Crustins show activity against Gram-positive bacteria. This study reports two Crustins, Al-crus 3 and Al-crus 7, from hydrothermal vent shrimp, Alvinocaris longirostris. Al-crus 3 and Al-crus 7 belong to Crustin Type IIa, with a similarity of about 51% at amino acid level. Antibacterial assays showed that Al-crus 3 mainly displayed activity against Gram-positive bacteria with MIC50 values of 10-25 μM. However, Al-crus 7 not only displayed activity against Gram-positive bacteria but also against Gram-negative bacteria Imipenem-resistant Acinetobacter baumannii, in a sensitive manner. Notably, in the effective antibacterial spectrum, Methicillin-sensitive Staphylococcus aureus, Escherichia coli (ESBLs) and Imipenem-resistant A. baumannii were drug-resistant pathogens. Narrowing down the sequence to the WAP domain, Al-crusWAP 3 and Al-crusWAP 7 demonstrated antibacterial activities but were weak. Additionally, the effects on bacteria did not significantly change after they were maintained at room temperature for 48 h. This indicated that Al-crus 3 and Al-crus 7 were relatively stable and convenient for transportation. Altogether, this study reported two new Crustins with specific characteristics. In particular, Al-crus 7 inhibited Gram-negative imipenem-resistant A. baumannii.

Marine collagen is gaining vast interest because of its high biocompatibility and lack of religious and social restrictions compared with collagen from terrestrial sources. In this study, lizardfish (Synodus macrops) scales were used to isolate acid-soluble collagen (ASC) and pepsin-soluble collagen (PSC). Both ASC and PSC were identified as type I collagen with intact triple-helix structures by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and spectroscopy. The ASC and PSC had high amino acids of 237 residues/1000 residues and 236 residues/1000 residues, respectively. Thus, the maximum transition temperature (Tmax) of ASC (43.2 °C) was higher than that of PSC (42.5 °C). Interestingly, the Tmax of both ASC and PSC was higher than that of rat tail collagen (39.4 °C) and calf skin collagen (35.0 °C), the terrestrial collagen. Solubility tests showed that both ASC and PSC exhibited high solubility in the acidic pH ranges. ASC was less susceptible to the "salting out" effect compared with PSC. Both collagen types were nontoxic to HaCaT and MC3T3-E1 cells, and ASC was associated with a higher cell viability than PSC. These results indicated that ASC from lizardfish scales could be an alternative to terrestrial sources of collagen, with potential for biomedical applications.

(1) Background: Chitooligosaccharides (COS) have numerous applications due to their excellent properties. Chitosan hydrolysis using chitosanases has been proposed as an advisable method for COS preparation. Although many chitosanases from various sources have been identified, the cold-adapted ones with high stability are still rather rare but required. (2) Methods: A novel chitosanase named CsnY from marine bacterium Renibacterium sp. Y82 was expressed in Escherichia coli, following sequence analysis. Then, the characterizations of recombinant CsnY purified through Ni-NTA affinity chromatography were conducted, including effects of pH and temperature, effects of metal ions and chemicals, and final product analysis. (3) Results: The GH46 family chitosanase CsnY possessed promising thermostability at broad temperature range (0-50 °C), and with optimal activity at 40 °C and pH 6.0, especially showing relatively high activity (over 80% of its maximum activity) at low temperatures (20-30 °C), which demonstrated the cold-adapted property. Common metal ions or chemicals had no obvious effect on CsnY except Mn2+ and Co2+. Finally, CsnY was determined to be an endo-type chitosanase generating chitodisaccharides and -trisaccharides as main products, whose total concentration reached 56.74 mM within 2 h against 2% (w/v) initial chitosan substrate. (4) Conclusions: The results suggest the cold-adapted CsnY with favorable stability has desirable potential for the industrial production of COS.

Representative marine materials such as biopolymers and bioceramics contain bioactive properties and are applied in regenerative medicine and tissue engineering. The marine organism-derived extracellular matrix (ECM), which consists of structural and functional molecules, has been studied as a biomaterial. It has been used to reconstruct tissues and improve biological functions. However, research on marine-derived extracellular vesicles (EVs) among marine functional materials is limited. Recent studies on marine-derived EVs were limited to eco-system studies using bacteria-released EVs. We aimed to expand the range of representative marine organisms such as fish, crustaceans, and echinoderms; establish the extraction process; and study the bioactivity capability of marine EVs. Results confirmed that marine organism ECM-anchored EVs (mEVs) have a similar morphology and cargos to those of EVs in land animals. To investigate physiological effects, lipopolysaccharide (LPS)-infected macrophages were treated with EVs derived from sea cucumber, fish, and shrimp. A comparison of the expression levels of inflammatory cytokine genes revealed that all types of mEVs alleviated pro-inflammatory cytokines, although to different degrees. Among them, the sea cucumber-derived EVs showed the strongest suppression ability. This study showed that research on EVs derived from various types of marine animals can lead to the development of high value-added therapeutics from discarded marine wastes.

Nannochloropsis oceanica can accumulate lipids and is a good source of polar lipids, which are emerging as new value-added compounds with high commercial value for the food, nutraceutical, and pharmaceutical industries. Some applications may limit the extraction solvents, such as food applications that require safe food-grade solvents, such as ethanol. However, the effect of using ethanol as an extraction solvent on the quality of the extracted polar lipidome, compared to other more traditional methods, is not yet well established. In this study, the polar lipid profile of N. oceanica extracts was obtained using different solvents, including chloroform/methanol (CM), dichloromethane/methanol (DM), dichloromethane/ethanol (DE), and ethanol (E), and evaluated by modern lipidomic methods using LC-MS/MS. Ultrasonic bath (E + USB)- and ultrasonic probe (E + USP)-assisted methodologies were implemented to increase the lipid extraction yields using ethanol. The polar lipid signature and antioxidant activity of DM, E + USB, and E + USP resemble conventional CM, demonstrating a similar extraction efficiency, while the DE and ethanol extracts were significantly different. Our results showed the impact of different extraction solvents in the polar lipid composition of the final extracts and demonstrated the feasibility of E + USB and E + USP as safe and food-grade sources of polar lipids, with the potential for high-added-value biotechnological applications.

Marine algae are recognised sources of bioactive compounds that have attracted great interest as nutritional supplements for aquaculture fish. Intensive rearing conditions often expose fish to husbandry-related stressors, rendering fish more susceptible to disease and reducing production yields. The present work evaluated the potential of two marine algae extracts (Fucus vesiculosus and Nannochloropsis gaditana) as nutritional supplements to mitigate stress effects in meagre (Argyrosomus regius) exposed to an acute handling stress (AS). A plant-based diet was used as a control, and three other diets were prepared, which were similar to the control diet but supplemented with 1% of each algal extract or a combination of the two extracts (0.5% each). The effects of supplemented diets on stress biomarkers, antioxidant enzyme activities, and immune response were analysed in fish exposed to AS after 4 weeks of feeding. Supplemented diets did not affect growth performance but the inclusion of F. vesiculosus promoted higher feed efficiency, as compared to the control group. Dietary algal extracts supplementation reduced plasma glucose levels, increased white blood cell counts, and reduced the expression of pro-inflammatory genes when compared with the control. N. gaditana supplementation led to a reduction in hepatic antioxidant enzyme activity and glutathione levels, while F. vesiculosus supplementation increased muscle glutathione reductase activity and reduced lipid peroxidation. These findings support the potential of algal extracts as nutraceuticals in aquafeeds to enhance the ability of fish to cope with husbandry-related stressful conditions and ultimately improve fish health and welfare.

Phytoene is a colourless natural carotenoid that absorbs UV light and provides antioxidant and anti-inflammatory activities as well as protection against photodamage. It is therefore valued for its skin health and aesthetic benefits by the cosmetic industry, as well as by the health food sector. The halotolerant green microalga Dunaliella salina is one of the richest sources of natural carotenoids. We have previously investigated the over-production of phytoene in D. salina after cultivation with the well-characterised mitosis inhibitor, chlorpropham. In this study, 15 herbicides with different modes of action were tested for their potential to promote phytoene accumulation. All herbicides showed different levels of capabilities to support phytoene over-production in D. salina. Most significantly, the two mitosis inhibitors tested in this study, propyzamide and chlorpropham, showed similar capacities to support the over-production of phytoene by D. salina cultures as phytoene desaturase inhibitors. The cellular content of phytoene increased by over 10-fold within 48 h of treatment with the mitosis inhibitors compared to untreated cultures. Results indicate a general effect of mitosis inhibitors on phytoene accumulation in D. salina. Furthermore, red light was found to significantly enhance the phytoene yield when used in combination with effective inhibitor treatments. Red light can be applied to maximize the production of phytoene from D. salina.

Breast cancer is the leading cause of death among women worldwide. Over the years, oxidative stress has been linked to the onset and progression of cancer. In addition to the classical histological classification, breast carcinomas are classified into phenotypes according to hormone receptors (estrogen receptor-RE-/progesterone receptor-PR) and growth factor receptor (human epidermal growth factor receptor-HER2) expression. Luminal tumors (ER/PR-positive/HER2-negative) are present in older patients with a better outcome. However, patients with HER2-positive or triple-negative breast cancer (TNBC) (ER/PR/HER2-negative) subtypes still represent highly aggressive behavior, metastasis, poor prognosis, and drug resistance. Therefore, new alternative therapies have become an urgent clinical need. In recent years, anticancer agents based on natural products have been receiving huge interest. In particular, carotenoids are natural compounds present in fruits and vegetables, but algae, bacteria, and archaea also produce them. The antioxidant properties of carotenoids have been studied during the last years due to their potential in preventing and treating multiple diseases, including cancer. Although the effect of carotenoids on breast cancer during in vitro and in vivo studies is promising, clinical trials are still inconclusive. The haloarchaeal carotenoid bacterioruberin holds great promise to the future of biomedicine due to its particular structure, and antioxidant activity. However, much work remains to be performed to draw firm conclusions. This review summarizes the current knowledge on pre-clinical and clinical analysis on the use of carotenoids as chemopreventive and chemotherapeutic agents in breast cancer, highlighting the most recent results regarding the use of bacterioruberin from haloarchaea.

Norovirus infections belong to the most common causes of human gastroenteritis worldwide and epidemic outbreaks are responsible for hundreds of thousands of deaths annually. In humans, noroviruses are known to bind to gastrointestinal epithelia via recognition of blood-group active mucin-type O-glycans. Considering the involvement of l-α-fucose residues in these glycans, their high valency on epithelial surfaces far surpasses the low affinity, though specific interactions of monovalent milk oligosaccharides. Based on these findings, we attempted to identify polyfucoses (fucans) with the capacity to block binding of the currently most prevalent norovirus strain GII.4 (Sydney, 2012, JX459908) to human and animal gastrointestinal mucins. We provide evidence that inhibitory effects on capsid binding are exerted in a competitive manner by α-fucosyl residues on Fucus vesiculosus fucoidan, but also on the galacto-fucan from Undaria pinnatifida and their oligo-fucose processing products. Insight into novel structural aspects of fucoidan and derived oligosaccharides from low-mass Undaria pinnatifida were revealed by GCMS and MALDI mass spectrometry. In targeting noroviral spread attenuation, this study provides first steps towards a prophylactic food additive that is produced from algal species.

C-phycoerythrin (C-PE) is a phycobiliprotein that prevents oxidative stress and cell damage. The aim of this study was to evaluate whether C-PE also counteracts endoplasmic reticulum (ER) stress as a mechanism contributing to its nephroprotective activity. After C-PE was purified from Phormidium persicinum by using size exclusion chromatography, it was characterized by spectrometry and fluorometry. A mouse model of HgCl2-induced acute kidney injury (AKI) was used to assess the effect of C-PE treatment (at 25, 50, or 100 mg/kg of body weight) on oxidative stress, the redox environment, and renal damage. ER stress was examined with the same model and C-PE treatment at 100 mg/kg. C-PE diminished oxidative stress and cell damage in a dose-dependent manner by impeding the decrease in expression of nephrin and podocin normally caused by mercury intoxication. It reduced ER stress by preventing the activation of the inositol-requiring enzyme-1α (IRE1α) pathway and avoiding caspase-mediated cell death, while leaving the expression of protein kinase RNA-like ER kinase (PERK) and activating transcription factor 6α (ATF6α) pathways unmodified. Hence, C-PE exhibited a nephroprotective effect on HgCl2-induced AKI by reducing oxidative stress and ER stress.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating digestive system carcinoma with high incidence and death rates. PDAC cells are dependent on the Gln metabolism, which can preferentially utilize glutamic oxaloacetate transaminase 1 (GOT1) to maintain the redox homeostasis of cancer cells. Therefore, small molecule inhibitors targeting GOT1 can be used as a new strategy for developing cancer therapies. In this study, 18 butyrolactone derivatives (1-18) were isolated from a marine-derived Aspergillus terreus, and asperteretone B (5), aspulvinone H (AH, 6), and (+)-3',3'-di-(dimethylallyl)-butyrolactone II (12) were discovered to possess significant GOT1-inhibitory activities in vitro, with IC50 values of (19.16 ± 0.15), (5.91 ± 0.04), and (26.38 ± 0.1) µM, respectively. Significantly, the molecular mechanism of the crystal structure of GOT1-AH was elucidated, wherein AH and the cofactor pyrido-aldehyde 5-phosphate competitively bound to the active sites of GOT1. More importantly, although the crystal structure of GOT1 has been discovered, the complex structure of GOT1 and its inhibitors has never been obtained, and the crystal structure of GOT1-AH is the first reported complex structure of GOT1/inhibitor. Further in vitro biological study indicated that AH could suppress glutamine metabolism, making PDAC cells sensitive to oxidative stress and inhibiting cell proliferation. More significantly, AH exhibited potent in vivo antitumor activity in an SW1990-cell-induced xenograft model. These findings suggest that AH could be considered as a promising lead molecule for the development of anti-PDAC agents.

Microglia M1 phenotype causes HPA axis hyperactivity, neurotransmitter dysfunction, and production of proinflammatory mediators and oxidants, which may contribute to the etiology of depression and neurodegenerative diseases. Eicosapentaenoic acid (EPA) may counteract neuroinflammation by increasing n-3 docosapentaenoic acid (DPA). However, the cellular and molecular mechanisms of DPA, as well as whether it can exert antineuroinflammatory and neuroprotective effects, are unknown. The present study first evaluated DPA's antineuroinflammatory effects in lipopolysaccharide (LPS)-activated BV2 microglia. The results showed that 50 μM DPA significantly decreased BV2 cell viability after 100 ng/mL LPS stimulation, which was associated with significant downregulation of microglia M1 phenotype markers and proinflammatory cytokines but upregulation of M2 markers and anti-inflammatory cytokine. Then, DPA inhibited the activation of mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) p65 pathways, which results were similar to the effects of NF-κB inhibitor, a positive control. Second, BV2 cell supernatant was cultured with differentiated SH-SY5Y neurons. The results showed that the supernatant from LPS-activated BV2 cells significantly decreased SH-SY5Y cell viability and brain-derived neurotrophic factor (BDNF), TrkB, p-AKT, and PI3K expression, which were significantly reversed by DPA pretreatment. Furthermore, DPA neuroprotection was abrogated by BDNF-SiRNA. Therefore, n-3 DPA may protect neurons from neuroinflammation-induced damage by balancing microglia M1 and M2 polarizations, inhibiting microglia-NF-κB and MAPK p38 while activating neuron-BDNF/TrkB-PI3K/AKT pathways.

Alginate, a natural polysaccharide derived from brown seaweed, is finding multiple applications in biomedicine via its transformation through chemical, physical, and, increasingly, enzymatic processes. In this study a novel alginate lyase, AlyDS44, was purified and characterized from a marine actinobacterium, Streptomyces luridiscabiei, which was isolated from decomposing seaweed. The purified enzyme had a specific activity of 108.6 U/mg, with a molecular weight of 28.6 kDa, and was composed of 260 amino acid residues. AlyDS44 is a bifunctional alginate lyase, active on both polyguluronate and polymannuronate, though it preferentially degrades polyguluronate. The optimal pH of this enzyme is 8.5 and the optimal temperature is 45 °C. It is a salt-tolerant alginate lyase with an optimal activity at 0.6 M NaCl. Metal ions Mn2+, Co2+, and Fe2+ increased the alginate degrading activity, but it was inhibited in the presence of Zn2+ and Cu2+. The highly conserved regions of its amino acid sequences indicated that AlyDS44 belongs to the polysaccharide lyase family 7. The main breakdown products of the enzyme on alginate were disaccharides, trisaccharides, and tetrasaccharides, which demonstrated that this enzyme acted as an endo-type alginate lyase. AlyDS44 is a novel enzyme, with the potential for efficient production of alginate oligosaccharides with low degrees of polymerization.

One of the challenges to the management of severe asthma is the poor therapeutic response to treatment with glucocorticosteroids. Compounds derived from marine sources have received increasing interest in recent years due to their prominent biologically active properties for biomedical applications, as well as their sustainability and safety for drug development. Based on the pathobiological features associated with glucocorticoid resistance in severe asthma, many studies have already described many glucocorticoid resistance mechanisms as potential therapeutic targets. On the other hand, in the last decade, many studies described the potentially anti-inflammatory effects of marine-derived biologically active compounds. Analyzing the underlying anti-inflammatory mechanisms of action for these marine-derived biologically active compounds, we observed some of the targeted pathogenic molecular mechanisms similar to those described in glucocorticoid (GC) resistant asthma. This article gathers the marine-derived compounds targeting pathogenic molecular mechanism involved in GC resistant asthma and provides a basis for the development of effective marine-derived drugs.

One strain-many compounds (OSMAC) manipulation of the sponge-derived fungus Pestalotiopsis heterocornis XWS03F09 resulted in the production of new secondary metabolites. The chemical study of the fermentation, cultivated on 3% artificial sea salt in the rice media, led to the isolation of twelve compounds, including eight new polyketide derivatives, heterocornols Q-X (1-8), one new ceramide (9), and three known analogues (10-12). The structures and absolute configurations of the new compounds were elucidated by spectroscopic data and calculated ECD analysis. Heterocornols Q (1) and R (2) are novel 6/5/7/5 tetracyclic polyketide derivatives featuring dihydroisobenzofuran and benzo-fused dioxabicyclo [4.2.1] nonane system, which might be derived from the acetyl-CoA by epoxidation, polyene cyclization, and rearrangement to form the core skeleton. Compound 12 showed moderate or weak antimicrobial activities against with MIC values ranging from 25 to 100 μg/mL. Heterocornols T and X (7 and 8) could inhibit the production of LPS-induced NO significantly, comparable to dexamethasone. Further Western blotting analysis showed 7 and 8 markedly suppressed the iNOS protein expression in LPS-induced RAW 264.7 cells in a dose-dependent manner. The result showed that 7 and 8 might serve as potential leads for development of anti-inflammatory activity.

The sponge metabolite ancorinoside B was prepared for the first time in 16 steps and 4% yield. It features a β-d-galactopyranosyl-(1→4)-β-d-glucuronic acid tethered to a d-aspartic acid-derived tetramic acid. Key steps were the synthesis of a fully protected d-lactose derived thioglycoside, its attachment to a C20-aldehyde spacer, functionalization of the latter with a terminal N-(β-ketoacyl)-d-aspartate, and a basic Dieckmann cyclization to close the pyrrolidin-2,4-dione ring with concomitant global deprotection. Ancorinoside B exhibited multiple biological effects of medicinal interest. It inhibited the secretion of the cancer metastasis-relevant matrix metalloproteinases MMP-2 and MMP-9, and also the growth of Staphylococcus aureus biofilms by ca 87% when applied at concentrations as low as 0.5 µg/mL. This concentration is far below its MIC of ca 67 µg/mL and thus unlikely to induce bacterial resistance. It also led to a 67% dispersion of preformed S. aureus biofilms when applied at a concentration of ca 2 µg/mL. Ancorinoside B might thus be an interesting candidate for the control of the general hospital, catheter, or joint protheses infections.

In a previous study, we found that the collagen peptides prepared from the by-products of Bester sturgeon had an inhibitory effect on elevated blood glucose levels in a glucose tolerance test with ICR mice. In the present study, we examine the mechanism of the effect of sturgeon collagen peptides (SCPs) in detail. When glucose was orally administered to mice along with the SCPs, it was found that the glucose remained in the stomach for a longer time. In the above tests, the amount of glucose excreted in the feces of mice also increased. On the contrary, it was revealed that the SCPs have a dipeptidyl-peptidase-IV (DPP-IV) inhibitory ability in an in vitro test. In subsequent oral and intravenous glucose administration tests, glucagon-like peptide-1 (GLP-1) and insulin levels in the blood of mice were maintained at high levels. These results suggested the following three mechanisms: SCPs slow the rate of transportation of glucose from the stomach into the small intestine, resulting in delayed glucose absorption; SCPs suppress the absorption of glucose in the small intestine and excrete it from the body; SCPs inhibit DPP-IV in the blood and maintain a high GLP-1 level in blood, which in turn stimulates insulin secretion.

Raf kinase inhibitory protein (RKIP) is an essential regulator of the Ras/Raf-1/MEK/ERK signaling cascade and functions by directly interacting with the Raf-1 kinase. The abnormal expression of RKIP is linked with numerous diseases including cancers, Alzheimer's and diabetic nephropathy. Interestingly, RKIP also plays an indispensable role as a tumor suppressor, thus making it an attractive therapeutic target. To date, only a few small molecules have been reported to modulate the activity of RKIP, and there is a need to explore additional scaffolds. In order to achieve this objective, a pharmacophore model was generated that explores the features of locostatin, the most potent RKIP modulator. Correspondingly, the developed model was subjected to screening, and the mapped compounds from Marine Natural Products (MNP) library were retrieved. The mapped MNPs after ensuing drug-likeness filtration were escalated for molecular docking, where locostatin was regarded as a reference. The MNPs exhibiting higher docking scores than locostatin were considered for molecular dynamics simulations, and their binding affinity towards RKIP was computed via MM/PBSA. A total of five molecules revealed significantly better binding free energy scores than compared to locostatin and, therefore, were reckoned as hits. The hits from the present in silico investigation could act as potent RKIP modulators and disrupt interactions of RKIP with its binding proteins. Furthermore, the identification of potent modulators from marine natural habitat can act as a future drug-discovery source.

This study provides a review of all isolated natural products (NPs) reported for sponges within the order Verongiida (1960 to May 2020) and includes a comprehensive compilation of their geographic and physico-chemical parameters. Physico-chemical parameters were used in this study to infer pharmacokinetic properties as well as the potential pharmaceutical potential of NPs from this order of marine sponge. In addition, a network analysis for the NPs produced by the Verongiida sponges was applied to systematically explore the chemical space relationships between taxonomy, secondary metabolite and drug score variables, allowing for the identification of differences and correlations within a dataset. The use of scaffold networks as well as bipartite relationship networks provided a platform to explore chemical diversity as well as the use of chemical similarity networks to link pharmacokinetic properties with structural similarity. This study paves the way for future applications of network analysis procedures in the field of natural products for any order or family.

A systematic chemical investigation of the deep-sea-derived fungus Penicillium solitum MCCC 3A00215 resulted in the isolation of one novel polyketide (1), two new alkaloids (2 and 3), and 22 known (4-25) compounds. The structures of the new compounds were established mainly on the basis of exhaustive analysis of 1D and 2D NMR data. Viridicatol (13) displayed moderate anti-tumor activities against PANC-1, Hela, and A549 cells with IC50 values of around 20 μM. Moreover, 13 displayed potent in vitro anti-food allergic activity with an IC50 value of 13 μM, compared to that of 92 μM for the positive control, loratadine, while indole-3-acetic acid methyl ester (9) and penicopeptide A (10) showed moderate effects (IC50 = 50 and 58 μM, respectively).

Neuroblastoma (NB) is a common cancer in childhood, and lethal in its high-risk form, primarily because of its high metastatic potential. Targeting cancer cell migration, and thus preventing metastasis formation, is the rationale for more effective cancer therapy against NB. Previous studies have described the leaf extract from Posidonia oceanica marine plant (POE) as an antioxidant, anti-inflammatory agent and inhibitor of cancer cell migration. This study aims to examine the POE anti-migratory role in human SH-SY5Y neuroblastoma cells and the underlying mechanisms of action. Wound healing and gelatin zymography assays showed that POE at early times inhibits cell migration and reduces pro-MMP-2 release into culture medium. By monitoring expression level of key autophagy markers by Western blot assay, a correlation between POE-induced cell migration inhibition and autophagy activation was demonstrated. Cell morphology and immunofluorescence analyses showed that POE induces neurite formation and neuronal differentiation at later times. These results suggest POE might act against cell migration by triggering early nontoxic autophagy. The POE-induced cellular morphological change toward cell differentiation might contribute to prolonging the phytocomplex anti-migratory effect to later times. Overall, these results encourage future in vivo studies to test POE applicability in neuroblastoma treatment.

Caulerpa racemosa (sea grapes) and Ulva lactuca (sea lettuces) are edible green seaweeds and good sources of bioactive compounds for future foods, nutraceuticals and cosmeceutical industries. In the present study, we determined nutritional values and investigated the recovery of bioactive compounds from C. racemosa and U. lactuca using hot water extraction (HWE) and subcritical water extraction (SWE) at different extraction temperatures (110 to 230 °C). Besides significantly higher extraction yield, SWE processes also give higher protein, sugar, total phenolic (TPC), saponin (TSC), flavonoid contents (TFC) and antioxidant activities as compared to the conventional HWE process. When SWE process was applied, the highest TPC, TSC and TFC values were obtained from U. lactuca hydrolyzed at reaction temperature 230 °C with the value of 39.82 ± 0.32 GAE mg/g, 13.22 ± 0.33 DE mg/g and 6.5 ± 0.47 QE mg/g, respectively. In addition, it also showed the highest antioxidant activity with values of 5.45 ± 0.11 ascorbic acid equivalents (AAE) mg/g and 8.03 ± 0.06 trolox equivalents (TE) mg/g for ABTS and total antioxidant, respectively. The highest phenolic acids in U. lactuca were gallic acid and vanillic acid. Cytotoxic assays demonstrated that C. racemosa and U. lactuca hydrolysates obtained by HWE and SWE did not show any toxic effect on RAW 264.7 cells at tested concentrations after 24 h and 48 h of treatment (p < 0.05), suggesting that both hydrolysates were safe and non-toxic for application in foods, cosmeceuticals and nutraceuticals products. In addition, the results of this study demonstrated the potential of SWE for the production of high-quality seaweed hydrolysates. Collectively, this study shows the potential of under-exploited tropical green seaweed resources as potential antioxidants in nutraceutical and cosmeceutical products.

The Hantaan orthohantavirus (genovariant Amur-AMRV) is a rodent-borne zoonotic virus; it is the causative agent of haemorrhagic fever with renal syndrome in humans. The currently limited therapeutic options require the development of effective anti-orthohantavirus drugs. The ability of native fucoidan from Fucus evanescens (FeF) and its enzymatically prepared high-molecular-weight (FeHMP) and low-molecular-weight (FeLMP) fractions to inhibit different stages of AMRV infection in Vero cells was studied. The structures of derivatives obtained were determined using nuclear magnetic resonance (NMR) spectroscopy. We found that fucoidan and its derivatives exhibited significant antiviral activity by affecting the early stages of the AMRV lifecycle, notably virus attachment and penetration. The FeHMP and FeLMP fractions showed the highest anti-adsorption activity by inhibiting AMRV focus formation, with a selective index (SI) > 110; FeF had an SI of ~70. The FeLMP fraction showed a greater virucidal effect compared with FeF and the FeHMP fraction. It was shown by molecular docking that 2O-sulphated fucotetrasaccharide, a main component of the FeLMP fraction, is able to bind with the AMRV envelope glycoproteins Gn/Gc and with integrin β3 to prevent virus-cell interactions. The relatively small size of these sites of interactions explains the higher anti-AMRV activity of the FeLMP fraction.

During the processes of primary and secondary endosymbiosis, different microalgae evolved to synthesis different storage polysaccharides. In stramenopiles, the main storage polysaccharides are β-1,3-glucan, or laminarin, in vacuoles. Currently, laminarin is gaining considerable attention due to its application in the food, cosmetic and pharmaceuticals industries, and also its importance in global biogeochemical cycles (especially in the ocean carbon cycle). In this review, the structures, composition, contents, and bioactivity of laminarin were summarized in different algae. It was shown that the general features of laminarin are species-dependence. Furthermore, the proposed biosynthesis and catabolism pathways of laminarin, functions of key genes, and diel regulation of laminarin were also depicted and comprehensively discussed for the first time. However, the complete pathways, functions of genes, and diel regulatory mechanisms of laminarin require more biomolecular studies. This review provides more useful information and identifies the knowledge gap regarding the future studies of laminarin and its applications.

Inflammation is the body's defense reaction in response to stimulations and is the basis of various physiological and pathological processes. However, chronic inflammation is undesirable and closely related to the occurrence and development of diseases. The ocean gives birth to unique and diverse bioactive substances, which have gained special attention and been a focus for anti-inflammatory drug development. So far, numerous promising bioactive substances have been obtained from various marine organisms such as marine bacteria and fungi, sponges, algae, and coral. This review covers 71 bioactive substances described during 2015-2020, including the structures (65 of which), species sources, evaluation models and anti-inflammatory activities of these substances. This review aims to provide some reference for the research progress of marine-organism-derived anti-inflammatory metabolites and give more research impetus for their conversion to novel anti-inflammatory drugs.

Production of sponge-derived bioactive compounds in vitro has been proposed as an alternative to wild harvest, aquaculture, and chemical synthesis to meet the demands of clinical drug development and manufacture. Until recently, this was not possible because there were no marine invertebrate cell lines. Recent breakthroughs in the development of sponge cell lines and rapid cell division in improved nutrient media now make this approach a viable option. We hypothesized that three-dimensional (3-D) cell cultures would better represent how sponges function in nature, including the production of bioactive compounds. We successfully cultured sponge cells in 3-D matrices using FibraCel® disks, thin hydrogel layers, and gel microdroplets (GMDs). For in vitro production of bioactive compounds, the use of GMDs is recommended. Nutrients and sponge products rapidly diffuse into and out of the 3-D matrix, the GMDs may be scaled up in spinner flasks, and cells and/or secreted products can be easily recovered. Research on scale-up and production is in progress in our laboratory.

Until now, the red algae Gelidium sesquipedale has been primarily exploited for agar production, leaving an undervalued biomass. In this work, the use of eco-friendly approaches employing ultrasound-assisted extraction (UAE) and green solvents was investigated to valorize the algal minor compounds. The green methods used herein showed an attractive alternative to efficiently extract a broad spectrum of bioactive compounds in short extraction times (15 to 30 min vs. 8 h of the conventional method). Using the best UAE conditions, red seaweed extracts were characterized in terms of total phenolics (189.3 ± 11.7 mg GAE/100 g dw), flavonoids (310.7 ± 9.7 mg QE/100 g dw), mycosporine-like amino acids (MAAs) (Σ MAAs = 1271 mg/100 g dw), and phycobiliproteins (72.4 ± 0.5 mg/100 g dw). Additionally, produced algal extracts exhibited interesting antioxidant and anti-enzymatic activities for potential applications in medical and/or cosmetic products. Thus, this study provides the basis to reach a superior valorization of algal biomass by using alternative methods to extract biologically active compounds following eco-friendly approaches. Moreover, the strategies developed not only open new possibilities for the commercial use of Gelidium sesquipedale, but also for the valorization of different algae species since the techniques established can be easily adapted.

Microalgae are often called "sustainable biofactories" due to their dual potential to mitigate atmospheric carbon dioxide and produce a great diversity of high-value compounds. Nevertheless, the successful exploitation of microalgae as biofactories for industrial scale is dependent on choosing the right microalga and optimum growth conditions. Due to the rich biodiversity of microalgae, a screening pipeline should be developed to perform microalgal strain selection exploring their growth, robustness, and metabolite production. Current prospects in microalgal biotechnology are turning their focus to high-value lipids for pharmaceutic, nutraceutic, and cosmetic products. Within microalgal lipid fraction, polyunsaturated fatty acids and carotenoids are broadly recognized for their vital functions in human organisms. Microalgal-derived phytosterols are still an underexploited lipid resource despite presenting promising biological activities, including neuroprotective, anti-inflammatory, anti-cancer, neuromodulatory, immunomodulatory, and apoptosis inductive effects. To modulate microalgal biochemical composition, according to the intended field of application, it is important to know the contribution of each cultivation factor, or their combined effects, for the wanted product accumulation. Microalgae have a vital role to play in future low-carbon economy. Since microalgal biodiesel is still costly, it is desirable to explore the potential of oleaginous species for its high-value lipids which present great global market prospects.

Presently, there is a high demand for nutritionally enhanced foods, so it is a current challenge to look at new raw food sources that can supplement beneficially the human diet. The nutritional profile and key secondary metabolites of red seaweeds (Rhodophyta) are gaining interest because of this challenge. In this context, the possible use of the red seaweed Chondracanthus teedei var. lusitanicus (Gigartinales) as a novel nutraceutical source was investigated. As a result, we highlight the high mineral content of this seaweed, representing 29.35 g 100 g-1 of its dry weight (DW). Despite the low levels of calcium and phosphorus (0.26 and 0.20 g 100 g-1 DW, respectively), this seaweed is an interesting source of nitrogen and potassium (2.13 and 2.29 g-1 DW, accordingly). Furthermore, the high content of carbohydrates (56.03 g 100 g-1 DW), which acts as dietary fibers, confers a low caloric content of this raw food source. Thus, this study demonstrates that C. teedei var. lusitanicus is in fact an unexploited potential resource with the capability to provide key minerals to the human diet with promising nutraceutical properties.

Four new anthraquinone derivatives, namely saliniquinones G-I (1-3) and heraclemycin E (4), were obtained from the Antarctic marine-derived actinomycete Nocardiopsis aegyptia HDN19-252, guided by the Global Natural Products Social (GNPS) molecular networking platform. Their structures, including absolute configurations, were elucidated by extensive NMR, MS, and ECD analyses. Compounds 1 and 2 showed promising inhibitory activity against six tested bacterial strains, including methicillin-resistant coagulase-negative staphylococci (MRCNS), with MIC values ranging from 3.1 to 12.5 μM.

Thraustochytrids are the most promising microbial source for the commercial production of docosahexaenoic acid (DHA) for its application in the human health, aquaculture, and nutraceutical sectors. The present study isolated 127 thraustochytrid strains from mangrove habitats of the south Andaman Islands, India to study their diversity, polyunsaturated fatty acids (PUFAs), and biotechnological potential. The predominant strains were identified as belonging to two major genera (Thraustochytrium, Aurantiochytrium) based on morphological and molecular characteristics. The strain ANVKK-06 produced the maximum biomass of 5.42 g·L-1, while ANVKK-03 exhibited the maximum total lipid (71.03%). Omega-3 PUFAs such as eicosapentaenoic acid (EPA) accumulated up to 11.03% in ANVKK-04, docosapentaenoic acid (DPA) up to 8.65% in ANVKK-07, and DHA up to 47.19% in ANVKK-06. ANVKK-06 showed the maximum scavenging activity (84.79 ± 2.30%) while ANVKK-03 and ANVKK-10 displayed the highest antibacterial activity against human and fish pathogens, S. aureus (18.69 ± 1.2 mm) and V. parahaemolyticus (18.31 ± 1.0 mm), respectively. All strains were non-toxic as evident by negative blood agar hemolysis, thus, the thraustochytrids are suggested to be a potential source of DHA for application in the health care of human and fish.

Paralytic shellfish poisoning (PSP) occurs when shellfish contaminated with saxitoxin or equivalent paralytic shellfish toxins (PSTs) are ingested. In British Columbia, Canada, documented poisonings are increasing in frequency based on 62 investigations identified from 1941-2020. Two PSP investigations were reported between 1941 and 1960 compared to 31 since 2001 (p < 0.0001) coincident with rising global temperatures (r2 = 0.76, p < 0.006). The majority of PSP investigations (71%) and cases (69%) were linked to self-harvested shellfish. Far more investigations involved harvests by indigenous communities (24%) than by commercial and recreational groups. Single-case-exposure investigations increased by more than 3.5 times in the decade 2011-2020 compared to previous periods. Clams (47%); mussels (26%); oysters (14%); scallops (6%); and, in more recent years, crabs (4%) were linked to illnesses. To guide understanding of self-harvesting consumption risks, we recommend collecting data to determine when PST-producing algae are present in high concentrations, improving the quality of data in online shellfish harvest maps to include dates of last testing; biotoxin testing results; and a description of bivalve species tested. Over reliance on toxin results in biomonitored species may not address actual consumption risks for unmonitored species harvested from the same area. We further recommend introducing phytoplankton monitoring in remote indigenous communities where self-harvesting is common and toxin testing is unavailable, as well as continuing participatory education about biotoxin risks in seafoods.

Turbo cornutus, the horned turban sea snail, is found along the intertidal and basaltic shorelines of Jeju Island, Korea. T. cornutus feeds on seaweeds (e.g., Undaria sp., and Ecklonia sp.) composed of diverse antioxidants. This study identified potential antioxidant properties from T. cornutus viscera tissues. Diverse extracts were evaluated for their hydrogen peroxide (H2O2) scavenging activities. T. cornutus viscera protamex-assisted extracts (TVP) were purified by gel filtration chromatography (GFC), and potential antioxidant properties were analyzed for their amino acid sequences and its peroxidase inhibition effects by in silico molecular docking and in vitro analysis. According to the results, T. cornutus viscera tissues are composed of many protein contents with each over 50%. Among the extracts, TVP possessed the highest H2O2 scavenging activity. In addition, TVP-GFC-3 significantly decreased intracellular reactive oxygen species (ROS) levels and increased cell viability in H2O2-treated HepG2 cells without cytotoxicity. TVP-GFC-3 comprises nine low molecular bioactive peptides (ELR, VGPQ, TDY, ALPHA, PAH, VDY, WSDK, VFSP, and FAPQY). Notably, the peptides dock to the active site of the myeloperoxidase (MPO), especially TDY and FAPQY showed the MPO inhibition effects with IC50 values of 646.0 ± 45.0 µM and 57.1 ± 17.7 µM, respectively. Altogether, our findings demonstrated that T. cornutus viscera have potential antioxidant properties that can be used as high value-added ingredients.

LC-MS/MS-based molecular networking facilitated the targeted isolation of a new cyclic hexadepsipeptide, cymodepsipeptide (1), and two known analogues, RF-2691A (2) and RF-2691B (3), from the fungus Cymostachys sp. NBUF082 that was derived from a mesophotic zone Aaptos sponge collected near Apo Island. The constitution and configuration of 1 was elucidated through 1D and 2D NMR-spectroscopy, high resolution mass-spectrometry, and chemical degradations including Marfey's analysis and chiral HPLC. It was observed that 1 was moderately cytotoxic against CCRF-CEM human acute lymphocytic leukemia cells in vitro with the IC50 value of 9.2 ± 1.1 μM.