Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Sonneradon A (SDA), a new compound first extracted from the edible fruits of mangrove Sonneratia apetala, showed remarkable antiaging activity. However, the role of SDA in antiaging remains unclear. In this article, we studied the function of SDA in antiaging by using the animal model Caenorhabditis elegans. Results showed that SDA inhibited production of reactive oxygen species (ROS) by 53%, and reduced the accumulation of aging markers such as lipids and lipofuscins. Moreover, SDA also enhanced the innate immune response to Pseudomonas aeruginosa infection. Genetic analysis of a series of mutants showed that SDA extended the lifespan of the mutants of eat-2 and glp-1. Together, this effect may be related to the enhanced resistance to oxidative stress via mitochondrial and insulin/insulin-like growth factor-1 signaling (IIS) pathways. The results of this study provided new evidence for an antiaging effect of SDA in C. elegans, as well as insights into the implication of antiaging activity of SDA in higher organisms.

The structural diversity and unique physicochemical properties of sulphated polysaccharides of red algae carrageenans (CRGs), to a great extent, determine the wide range of their antiviral properties. This work aimed to compare the antiviral activities of different structural types of CRGs: against herpes simplex virus type 1 (HSV-1) and enterovirus (ECHO-1). We found that CRGs significantly increased the resistance of Vero cells to virus infection (preventive effect), directly affected virus particles (virucidal effect), inhibited the attachment and penetration of virus to cells, and were more effective against HSV-1. CRG1 showed the highest virucidal effect on HSV-1 particles with a selective index (SI) of 100. CRG2 exhibited the highest antiviral activity by inhibiting HSV-1 and ECHO-1 plaque formation, with a SI of 110 and 59, respectively, when it was added before virus infection. CRG2 also significantly reduced the attachment of HSV-1 and ECHO-1 to cells compared to other CRGs. It was shown by molecular docking that tetrasaccharides-CRGs are able to bind with the HSV-1 surface glycoprotein, gD, to prevent virus-cell interactions. The revealed differences in the effect of CRGs on different stages of the lifecycle of the viruses are apparently related to the structural features of the investigated compounds.

The marine environment is an important source of specialized metabolites with valuable biological activities. Xanthones are a relevant chemical class of specialized metabolites found in this environment due to their structural variety and their biological activities. In this work, a comprehensive literature review of marine xanthones reported up to now was performed. A large number of bioactive xanthone derivatives (169) were identified, and their structures, biological activities, and natural sources were described. To characterize the chemical space occupied by marine-derived xanthones, molecular descriptors were calculated. For the analysis of the molecular descriptors, the xanthone derivatives were grouped into five structural categories (simple, prenylated, O-heterocyclic, complex, and hydroxanthones) and six biological activities (antitumor, antibacterial, antidiabetic, antifungal, antiviral, and miscellaneous). Moreover, the natural product-likeness and the drug-likeness of marine xanthones were also assessed. Marine xanthone derivatives are rewarding bioactive compounds and constitute a promising starting point for the design of other novel bioactive molecules.

Ericaria crinita and Ericaria amentacea from the Adriatic Sea (Croatia) were investigated with respect to the presence of less-polar compounds for the first time after fractionation by solid-phase extraction (SPE). The composition of less-polar fractions of freeze-dried E. crinita (FdEc) and E. amentacea (FdEa) were analyzed by high-performance liquid chromatography-high-resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). The major identified compounds were: amides of higher aliphatic acids (palmitoleamide, linoleamide, palmitamide, oleamide and erucamide) and related compounds, carotenoid (fucoxanthin), chlorophyll derivatives (pheophytin a and b and their derivatives) and higher terpenes (loliolide, isoamijiol with its oxidation product), β-stigmasterol and (3β,6α)-14-methylergosta-8,24(28)-diene-3,6-diol). The toxic effects observed on the less-polar fractions obtained from Ericaria species on zebrafish Danio rerio embryos could be associated with the high abundance of all five detected amides. The antioxidant activity of the fractions was evaluated by means of five independent assays, including the reduction of the radical cation (ABTS), the oxygen radical absorbance capacity (ORAC), ferric-reducing antioxidant power (FRAP), the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay and the Folin-Ciocalteu method. A higher antioxidant activity of E. amentacea in comparison to that of the E. crinita fractions was found with IC50 concentrations of 0.072 and 1.177 mg/mL, respectively. The correlation between the activity and the chemical composition revealed that the synergistic effect of different compounds impacted their antioxidant response.

This study aimed to investigate the potential use of brown algae Sargassum polycystum as irreversible hydrocolloid (alginate) impression material. Potassium alginate extracted from Sargassum polycystum was prepared in three different compositions (14%, 15%, and 16%) and mixed with other standard components to form an alginate impression material. Prior to that, the purity of potassium alginate was quantified with Fourier Transform Infrared Spectroscopy (FTIR) analysis. As a control material, the alginate impression material from a commercially available product was used. All alginate impression materials were then applied to a die stone model. Dimensional accuracy was measured by calculating the mesiodistal width of incisors in the generated dental cast using a digital caliper 0.01 accuracy (five replications). In addition, to evaluate the dimensional stability, the impression results were poured at four different periods (immediately, 5 min, 10 min, and 15 min). An independent t-test was performed to compare the measurement results with p < 0.05 considered significant. Analytical results confirm that the impression material containing 15% potassium alginate gives the best dimensional accuracy similar to control (p > 0.05). Meanwhile, the optimal dimensional stability was produced in the impression material containing 16% potassium alginate. Our study suggested that brown algae Sargassum polycystum has a promising potential to be used as an alginate impression material in clinical application.

Melanin is a widely distributed and striking dark-colored pigment produced by countless living organisms. Although a wide range of bioactivities have been recognized, there are still major constraints in using melanin for biotechnological applications such as its fragmentary known chemical structure and its insolubility in inorganic and organic solvents. In this study, a bacterial culture of Streptomyces cavourensis SV 21 produced two distinct forms of melanin: (1) a particulate, insoluble form as well as (2) a rarely observed water-soluble form. The here presented novel, acid-free purification protocol of purified particulate melanin (PPM) and purified dissolved melanin (PDM) represents the basis for an in-depth comparison of their physicochemical and biological properties, which were compared to the traditional acid-based precipitation of melanin (AM) and to a synthetic melanin standard (SM). Our data show that the differences in solubility between PDM and PPM in aqueous solutions may be a result of different adjoining cation species, since the soluble PDM polymer is largely composed of Mg2+ ions and the insoluble PPM is dominated by Ca2+ ions. Furthermore, AM shared most properties with SM, which is likely attributed to a similar, acid-based production protocol. The here presented gentler approach of purifying melanin facilitates a new perspective of an intact form of soluble and insoluble melanin that is less chemical altered and thus closer to its original biological form.

Green nanotechnology is now accepted as an environmentally friendly and cost-effective advance with various biomedical applications. The cyanobacterium Synechocystis sp. is a unicellular spherical cyanobacterium with photo- and hetero-trophic capabilities. This study investigates the ability of this cyanobacterial species to produce silver nanoparticles (AgNPs) and the wound-healing properties of the produced nanoparticles in diabetic animals. METHODS: UV-visible and FT-IR spectroscopy and and electron microscopy techniques investigated AgNPs' producibility by Synechocystis sp. when supplemented with silver ion source. The produced AgNPs were evaluated for their antimicrobial, anti-oxidative, anti-inflammatory, and diabetic wound healing along with their angiogenesis potential. RESULTS: The cyanobacterium biosynthesized spherical AgNPs with a diameter range of 10 to 35 nm. The produced AgNPs exhibited wound-healing properties verified with increased contraction percentage, tensile strength and hydroxyproline level in incision diabetic wounded animals. AgNPs treatment decreased epithelialization period, amplified the wound closure percentage, and elevated collagen, hydroxyproline and hexosamine contents, which improved angiogenesis factors' contents (HIF-1α, TGF-β1 and VEGF) in excision wound models. AgNPs intensified catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities, and glutathione (GSH) and nitric oxide content and reduced malondialdehyde (MDA) level. IL-1β, IL-6, TNF-α, and NF-κB (the inflammatory mediators) were decreased with AgNPs' topical application. CONCLUSION: Biosynthesized AgNPs via Synechocystis sp. exhibited antimicrobial, anti-oxidative, anti-inflammatory, and angiogenesis promoting effects in diabetic wounded animals.

Clam heparinoid G2 (60.25 kDa) and its depolymerized derivatives DG1 (24.48 kDa) and DG2 (6.75 kDa) prepared from Coelomactra antiquata have been documented to have excellent fibrinolytic and anticoagulant activity. In this study, to further explore the antithrombotic activity of G2, DG1 and DG2, azure A, sheep plasma, and clot lytic rate assays were used to determine their anticoagulant and thrombolytic activity in vitro. The results indicated that the anticoagulant titer of G2 was approximately 70% that of heparin and the thrombolytic activity of DG2 was greater than G2, DG1, and heparin activities. Moreover, in a carrageenan-induced venous thrombosis model, oral administration of G2 and DG1 each at 20 mg/kg and 40 mg/kg for 7 days significantly reduced blacktail thrombus formation, increased tissue-type plasminogen activator, fibrin degradation products, and D-dimer levels, decreased von Willebrand factor and thromboxane B2 levels, and restored phylum and genus abundance changes of intestinal bacteria. DG2 had no antithrombotic effect. At 20 mg/kg, G2, DG1, and heparin had comparable antithrombotic activities, and DG1 at 40 mg/kg had more muscular antithrombotic activity than G2. Thus, DG1 could be an antithrombotic oral agent owing to its more robust antithrombotic activity and lower molecular weight.

Computer-aided drug design (CADD) techniques allow the identification of compounds capable of modulating protein functions in pathogenesis-related pathways, which is a promising line on drug discovery. Marine natural products (MNPs) are considered a rich source of bioactive compounds, as the oceans are home to much of the planet's biodiversity. Biodiversity is directly related to chemodiversity, which can inspire new drug discoveries. Therefore, natural products (NPs) in general, and MNPs in particular, have been used for decades as a source of inspiration for the design of new drugs. However, NPs present both opportunities and challenges. These difficulties can be technical, such as the need to dive or trawl to collect the organisms possessing the compounds, or biological, due to their particular marine habitats and the fact that they can be uncultivable in the laboratory. For all these difficulties, the contributions of CADD can play a very relevant role in simplifying their study, since, for example, no biological sample is needed to carry out an in-silico analysis. Therefore, the amount of natural product that needs to be used in the entire preclinical and clinical study is significantly reduced. Here, we exemplify how this combination between CADD and MNPs can help unlock their therapeutic potential. In this study, using a set of marine invertebrate molecules, we elucidate their possible molecular targets and associated therapeutic potential, establishing a pipeline that can be replicated in future studies.

Sponges are at the forefront of marine natural product research. In the deep sea, extreme conditions have driven secondary metabolite pathway evolution such that we might expect deep-sea sponges to yield a broad range of unique natural products. Here, we investigate the chemodiversity of a deep-sea tetractinellid sponge, Characella pachastrelloides, collected from ~800 m depth in Irish waters. First, we analyzed the MS/MS data obtained from fractions of this sponge on the GNPS public online platform to guide our exploration of its chemodiversity. Novel glycolipopeptides named characellides were previously isolated from the sponge and herein cyanocobalamin, a manufactured form of vitamin B12, not previously found in nature, was isolated in a large amount. We also identified several poecillastrins from the molecular network, a class of polyketide known to exhibit cytotoxicity. Light sensitivity prevented the isolation and characterization of these polyketides, but their presence was confirmed by characteristic NMR and MS signals. Finally, we isolated the new betaine 6-methylhercynine, which contains a unique methylation at C-2 of the imidazole ring. This compound showed potent cytotoxicity towards against HeLa (cervical cancer) cells.

Seven new xanthones, diaporthones A-G (1-7), together with 13 known analogues, including five mono- (8-14) and six dimeric xanthones (15-20), were obtained from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar structures were established by extensive spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HR-ESIMS). The absolute configurations of 1-7 were clearly identified by X-ray crystallographic analysis and calculation of the ECD Spectra. Compounds 15-20 showed significant anti-inflammatory activity with IC50 values between 6.3 and 8.0 μM. In addition, dimeric xanthones (15-20) showed selective cytotoxicity against T98G cell lines with IC50 values ranging from 19.5 to 78.0 μM.

Nereistoxin (NTX) is a marine toxin isolated from an annelid worm that lives along the coasts of Japan. Its insecticidal properties were discovered decades ago and this stimulated the development of a variety of insecticides such as Cartap that are readily transformed into NTX. One unusual feature of NTX is that it is a small cyclic molecule that contains a disulfide bond. In spite of its size, it acts as an antagonist at insect and mammalian nicotinic acetylcholine receptors (nAChRs). The functional importance of the disulfide bond was assessed by determining the effects of inserting a methylene group between the two sulfur atoms, creating dimethylaminodithiane (DMA-DT). We also assessed the effect of methylating the NTX and DMA-DT dimethylamino groups on binding to three vertebrate nAChRs. Radioligand receptor binding experiments were carried out using washed membranes from rat brain and fish (Torpedo) electric organ; [3H]-cytisine displacement was used to assess binding to the predominantly high affinity alpha4beta2 nAChRs and [125I]-alpha-bungarotoxin displacement was used to measure binding of NTX and analogs to the alpha7 and skeletal muscle type nAChRs. While the two quaternary nitrogen analogs, relative to their respective tertiary amines, displayed lower α4β2 nAChR binding affinities, both displayed much higher affinities for the Torpedo muscle nAChR and rat alpha7 brain receptors than their respective tertiary amine forms. The binding affinities of DMA-DT for the three nAChRs were lower than those of NTX and MeNTX. An AChBP mutant lacking the C loop disulfide bond that would potentially react with the NTX disulfide bond displayed an NTX affinity very similar to the parent AChBP. Inhibition of [3H]-epibatidine binding to the AChBPs was not affected by exposure to NTX or MeNTX for up to 24 hr prior to addition of the radioligand. Thus, the disulfide bond of NTX is not required to react with the vicinal disulfide in the AChBP C loop for inhibition of [3H]-epibatidine binding. However, a reversible disulfide interchange reaction of NTX with nAChRs might still occur, especially under reducing conditions. Labeled MeNTX, because it can be readily prepared with high specific radioactivity and possesses relatively high affinity for the nAChR-rich Torpedo nAChR, would be a useful probe to detect and identify any nereistoxin adducts.

Brown algae are ubiquitously distributed in the NW coastline of the Iberian Peninsula, where they stand as an underexploited resource. In this study, five solvents were applied to the extraction of pigments from nine brown algae, followed by their determination and quantification by HPLC-DAD. A total of 13 compounds were detected: Six were identified as chlorophylls, six were classified as xanthophylls, and one compound was reported as a carotene. Fucoxanthin was reported in all extracts, which is the most prominent pigment of these algae. Among them, L. saccharina and U. pinnatifida present the highest concentration of fucoxanthin (4.5-4.7 mg∙g-1 dry weight). Ethanol and acetone were revealed as the most efficient solvents for the extraction of pigments, showing a maximal value of 11.9 mg of total pigments per gram of dry alga obtained from the ethanolic extracts of H. elongata, followed by the acetonic extracts of L. ochroleuca. Indeed, ethanol was also revealed as the most efficient solvent according to its high extraction yield along all species evaluated. Our results supply insights into the pigment composition of brown algae, opening new perspectives on their commercial exploitation by food, pharmaceutical, and cosmeceutical industries.

Inducing the feeling of fullness via the regulation of satiety hormones presents an effective method for reducing excess energy intake and, in turn, preventing the development of obesity. In this study, the ability of blue whiting soluble protein hydrolysates (BWSPHs) and simulated gastrointestinal digested (SGID) BWSPHs, to modulate the secretion and/or production of satiety hormones, such as glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY), was assessed in murine enteroendocrine STC-1 cells. All BWSPHs (BW-SPH-A to BW-SPH-F) (1.0% w/v dw) increased active GLP-1 secretion and proglucagon production in STC-1 cells compared to the basal control (Krebs-Ringer buffer) (p < 0.05). The signaling pathway activated for GLP-1 secretion was also assessed. A significant increase in intracellular calcium levels was observed after incubation with all BWSPHs (p < 0.05) compared with the control, although none of the BWSPHs altered intracellular cyclic adenosine monophosphate (cAMP) concentrations. The secretagogue effect of the leading hydrolysate was diminished after SGID. Neither pre- nor post-SGID hydrolysates affected epithelial barrier integrity or stimulated interleukin (IL)-6 secretion in differentiated Caco-2/HT-29MTX co-cultured cells. These results suggest a role for BWSPH-derived peptides in satiety activity; however, these peptides may need to be protected by some means to avoid loss of activity during gastrointestinal transit.

Methicillin-resistant Staphylococcus aureus (MRSA) is highly concerning as a principal infection pathogen. The investigation of higher effective natural anti-MRSA agents from marine Streptomyces parvulus has led to the isolation of actinomycin D, that showed potential anti-MRSA activity with MIC and MBC values of 1 and 8 μg/mL, respectively. Proteomics-metabolomics analysis further demonstrated a total of 261 differential proteins and 144 differential metabolites induced by actinomycin D in MRSA, and the co-mapped correlation network of omics, indicated that actinomycin D induced the metabolism pathway of producing the antibiotic sensitivity in MRSA. Furthermore, the mRNA expression levels of the genes acnA, ebpS, clfA, icd, and gpmA related to the key differential proteins were down-regulated measured by qRT-PCR. Molecular docking predicted that actinomycin D was bound to the targets of the two key differential proteins AcnA and Icd by hydrogen bonds and interacted with multiple amino acid residues of the proteins. Thus, these findings will provide a basic understanding to further investigation of actinomycin D as a potential anti-MRSA agent.

Although the S8 family in the MEROPS database contains many peptidases, only a few S8 peptidases have been applied in the preparation of bioactive oligopeptides. Bovine bone collagen is a good source for preparing collagen oligopeptides, but has been so far rarely applied in collagen peptide preparation. Here, we characterized a novel S8 gelatinase, Aa2_1884, from marine bacterium Flocculibacter collagenilyticus SM1988T, and evaluated its potential application in the preparation of collagen oligopeptides from bovine bone collagen. Aa2_1884 is a multimodular S8 peptidase with a distinct domain architecture from other reported peptidases. The recombinant Aa2_1884 over-expressed in Escherichia coli showed high activity toward gelatin and denatured collagens, but no activity toward natural collagens, indicating that Aa2_1884 is a gelatinase. To evaluate the potential of Aa2_1884 in the preparation of collagen oligopeptides from bovine bone collagen, three enzymatic hydrolysis parameters, hydrolysis temperature, hydrolysis time and enzyme-substrate ratio (E/S), were optimized by single factor experiments, and the optimal hydrolysis conditions were determined to be reaction at 60 ℃ for 3 h with an E/S of 400 U/g. Under these conditions, the hydrolysis efficiency of bovine bone collagen by Aa2_1884 reached 95.3%. The resultant hydrolysate contained 97.8% peptides, in which peptides with a molecular weight lower than 1000 Da and 500 Da accounted for 55.1% and 39.5%, respectively, indicating that the hydrolysate was rich in oligopeptides. These results indicate that Aa2_1884 likely has a promising potential application in the preparation of collagen oligopeptide-rich hydrolysate from bovine bone collagen, which may provide a feasible way for the high-value utilization of bovine bone collagen.

Tetrodotoxin (TTX) is a crystalline, weakly basic, colorless organic substance and is one of the most potent marine toxins known. Although TTX was first isolated from pufferfish, it has been found in numerous other marine organisms and a few terrestrial species. Moreover, tetrodotoxication is still an important health problem today, as TTX has no known antidote. TTX poisonings were most commonly reported from Japan, Thailand, and China, but today the risk of TTX poisoning is spreading around the world. Recent studies have shown that TTX-containing fish are being found in other regions of the Pacific and in the Indian Ocean, as well as the Mediterranean Sea. This review aims to summarize pertinent information available to date on the structure, origin, distribution, mechanism of action of TTX and analytical methods used for the detection of TTX, as well as on TTX-containing organisms, symptoms of TTX poisoning, and incidence worldwide.

Schistosomiasis has been controlled for more than 40 years with a single drug, praziquantel, and only one molluscicide, niclosamide, raising concern of the possibility of the emergence of resistant strains. However, the molecular targets for both agents are thus far unknown. Consequently, the search for lead compounds from natural sources has been encouraged due to their diverse structure and function. Our search for natural compounds with potential use in schistosomiasis control led to the identification of an algal species, Laurencia dendroidea, whose extracts demonstrated significant activity toward both Schistosoma mansoni parasites and their intermediate host snails Biomphalaria glabrata. In the present study, three seaweed-derived halogenated sesquiterpenes, (-)-elatol, rogiolol, and obtusol are proposed as potential lead compounds for the development of anthelminthic drugs for the treatment of and pesticides for the environmental control of schistosomiasis. The three compounds were screened for their antischistosomal and molluscicidal activities. The screening revealed that rogiolol exhibits significant activity toward the survival of adult worms, and that all three compounds showed activity against S. mansoni cercariae and B. glabrata embryos. Biomonitored fractioning of L. dendroidea extracts indicated elatol as the most active compound toward cercariae larvae and snail embryos.

Colorectal carcinoma (CRC) is one of the major causes of cancer-related incidence and deaths. Here, we identified a novel antitumor peptide, P6, with a molecular weight of 2794.8 Da from a marine Chinese medicine, Arca inflata Reeve. The full amino acid sequence and secondary structure of P6 were determined by tandem mass de novo sequencing and circular dichroism spectroscopy, respectively. P6 markedly inhibited cell proliferation and colony formation, and induced apoptosis in CRC cells. Mechanistically, transcriptomics analysis and a serial functional evaluation showed that P6 induced colon cancer cell apoptosis through the activation of the p38-MAPK signaling pathway. Moreover, it was demonstrated that P6 exhibited antitumor effects in a tumor xenograft model, and induced cell cycle arrest in CRC cells in a concentration-dependent mode. These findings provide the first line of indication that P6 could be a potential therapeutic agent for CRC treatment.

Liver cancers, such as hepatocellular carcinoma (HCC), are a highly prevalent cause of cancer-related deaths. Current treatments to combat liver cancer are limited. (-)-Agelasidine A, a compound isolated from the methanol extract of Agelasnakamurai, a sesquiterpene guanidine derived from sea sponge, has antibacterial activity. We demonstrated its anticancer capabilities by researching the associated mechanism of (-)-agelasidine A in human liver cancer cells. We found that (-)-agelasidine A significantly reduced viability in Hep3B and HepG2 cells, and we determined that apoptosis was involved in the (-)-agelasidine A-induced Hep3B cell deaths. (-)-Agelasidine A activated caspases 9, 8, and 3, as well as PARP. This effect was reversed by caspase inhibitors, suggesting caspase-mediated apoptosis in the (-)-agelasidine A-treated Hep3B cells. Moreover, the reduced mitochondrial membrane potential (MMP) and the release of cytochrome c indicated that the (-)-agelasidine A-mediated mitochondrial apoptosis was mechanistic. (-)-Agelasidine A also increased apoptosis-associated proteins (DR4, DR5, FAS), which are related to extrinsic pathways. These events were accompanied by an increase in Bim and Bax, proteins that promote apoptosis, and a decrease in the antiapoptotic protein, Bcl-2. Furthermore, our results presented that (-)-agelasidine A treatment bridged the intrinsic and extrinsic apoptotic pathways. Western blot analysis of Hep3B cells treated with (-)-agelasidine A showed that endoplasmic reticulum (ER) stress-related proteins (GRP78, phosphorylated PERK, phosphorylated eIF2α, ATF4, truncated ATF6, and CHOP) were upregulated. Moreover, 4-PBA, an ER stress inhibitor, could also abrogate (-)-agelasidine A-induced cell viability reduction, annexin V+ apoptosis, death receptor (DR4, DR5, FAS) expression, mitochondrial dysfunction, and cytochrome c release. In conclusion, by activating ER stress, (-)-agelasidine A induced the extrinsic and intrinsic apoptotic pathways of human HCC.

Environmental microbes living in communities engage in complex interspecies interactions that are challenging to decipher. Nevertheless, the interactions provide the basis for shaping community structure and functioning, which is crucial for ecosystem service. In addition, microbial interactions facilitate specific adaptation and ecological evolution processes particularly essential for microbial communities dwelling in resource-limiting habitats, such as the deep oceans. Recent technological and knowledge advancements provide an opportunity for the study of interactions within complex microbial communities, such as those inhabiting deep-sea waters and sediments. The microbial interaction studies provide insights into developing new strategies for biotechnical applications. For example, cooperative microbial interactions drive the degradation of complex organic matter such as chitins and celluloses. Such microbiologically-driven biogeochemical processes stimulate creative designs in many applied sciences. Understanding the interaction processes and mechanisms provides the basis for the development of synthetic communities and consequently the achievement of specific community functions. Microbial community engineering has many application potentials, including the production of novel antibiotics, biofuels, and other valuable chemicals and biomaterials. It can also be developed into biotechniques for waste processing and environmental contaminant bioremediation. This review summarizes our current understanding of the microbial interaction mechanisms and emerging techniques for inferring interactions in deep-sea microbial communities, aiding in future biotechnological and therapeutic applications.

Glycation, and the resulting buildup of advanced glycation end products (AGEs), is recognized as a key driver of cumulative skin damage and skin aging. Dunaliella salina is a halophile microalga adapted to intense solar radiation through the production of carotenoids. We present a natural supercritical CO2 extract of Dunaliella salina rich in the colorless carotenoids phytoene and phytofluene. The extract exhibited antiglycation and anti-inflammatory activities in ex vivo testing, showing strongly reduced formation of N-ε-carboxy-methyl-lysine with exposure to methylglyoxal, reduced AGE receptor levels, and significantly reduced interleukins 6 and 8. In a placebo-controlled clinical study under intense solar exposure, the extract significantly reduced the skin's glycation scores and its sensitivity to histamine; key skin aging parameters were also significantly improved vs. placebo, including wrinkle counts and spots. These results demonstrate the value of this Dunaliella salina extract, rich in colorless carotenoids, as an antiglycative, anti-inflammatory, and antiaging active ingredient, including in high-irradiation contexts.

Within the Conidae family, the piscivorous Conus species have been a hotspot target for drug discovery. Here, we assess the relevance of Conus and their other feeding habits, and thus under distinctive evolutionary constraints, to highlight the potential of neglected molluscivorous and vermivorous species in biomedical research and pharmaceutical industry. By singling out the areas with inadequate Conus disquisition, such as the Tamil Nadu Coast and the Andaman Islands, research resources can be expanded and better protected through awareness. In this study, 728 Conus species and 190 species from three other genera (1 from Californiconus, 159 from Conasprella and 30 from Profundiconus) in the Conidae family are assessed. The phylogenetic relationships of the Conidae species are determined and their known feeding habits superimposed. The worm-hunting species appeared first, and later the mollusc- and fish-hunting species were derived independently in the Neogene period (around 23 million years ago). Interestingly, many Conus species in the warm and shallow waters become polyphagous, allowing them to hunt both fish and worms, given the opportunities. Such newly gained trait is multi originated. This is controversial, given the traditional idea that most Conus species are specialized to hunt certain prey categories. However, it shows the functional complexity and great potential of conopeptides from some worm-eating species. Pharmaceutical attempts and relevant omics data have been differentially obtained. Indeed, data from the fish-hunting species receive strong preference over the worm-hunting ones. Expectedly, conopeptides from the fish-hunting species are believed to include the most potential candidates for biomedical research. Our work revisits major findings throughout the Conus evolution and emphasizes the importance of increasing omics surveys complemented with further behavior observation studies. Hence, we claim that Conus species and their feeding habits are equally important, highlighting many places left for Conus exploration worldwide. We also discuss the Conotoxin drug discovery potentials and the urgency of protecting the bioresources of Conus species. In particular, some vermivorous species have demonstrated great potential in malaria therapy, while other conotoxins from several worm- and mollusc-eating species exhibited explicit correlation with SARS-CoV-2. Reclaiming idle data with new perspectives could also promote interdisciplinary studies in both virological and toxicological fields.

Marine rhodophyta are known to synthesize specific secondary metabolites, mycosporine-like amino acids (MAAs), to protect themselves from harmful UV-radiation. Shinorine and porphyra-334 are among the most abundant representatives of this compound class. In the present work, a novel approach for their isolation is described. As a first step, a fast centrifugal partition chromatography method, with an aqueous two-phase system comprising water, ethanol, ammonium sulfate and methanol in ascending mode, was developed to isolate the two MAAs from crude aqueous-methanolic extracts of three algal species within 90 min. The compounds could be isolated when just one of them was present in a sample or also both at the same time. By employing solid phase extraction as a second purification step, the individual MAAs were obtained in high purity and good quantity within a much shorter time frame than the established purification protocols, e.g., semi-preparative HPLC. For example, from 4 g Porphyra sp. (Nori) crude extract, 15.7 mg shinorine and 36.2 mg porphyra-334 were isolated. Both were highly pure, as confirmed by TLC, HPLC-MS and NMR analyses.

Marine algae are an excellent source of novel lectins. The isolation of lectins from marine algae expands the diversity in structure and carbohydrate specificities of lectins isolated from other sources. Marine algal lectins have been reported to have antiviral, antitumor, and antibacterial activity. Lectins are typically isolated from marine algae by grinding the algal tissue with liquid nitrogen and extracting with buffer and alcohol. While this method produces higher yields, it may not be sustainable for large-scale production, because a large amount of biomass is required to produce a minute amount of compound, and a significant amount of waste is generated during the extraction process. Therefore, non-destructive extraction using algal culture water could be used to ensure a continuous supply of lectins without exclusively disrupting the marine algae. This review discusses the traditional and recent advancements in algal lectin extraction methods over the last decade, as well as the steps required for large-scale production. The challenges and prospects of various extraction methods (destructive and non-destructive) are also discussed.

In this study, films of chitosan and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), a 2-aminothiophene derivative with great pharmacological potential, were prepared as a system for a topical formulation. 6CN-chitosan films were characterized by physicochemical analyses, such as Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electronic microscopy (SEM). Additionally, the antifungal potential of the films was evaluated in vitro against three species of Candida (C. albicans, C. tropicalis, and C. parapsilosis). The results of the FTIR and thermal analysis showed the incorporation of 6CN in the polymer matrix. In the diffractogram, the 6CN-chitosan films exhibited diffraction halos that were characteristic of amorphous structures, while the micrographs showed that 6CN particles were dispersed in the chitosan matrix, exhibiting pores and cracks on the film surface. In addition, the results of antifungal investigation demonstrated that 6CN-chitosan films were effective against Candida species showing potential for application as a new antifungal drug.

Malaysia has a long coastline surrounded by various islands, including North Borneo, that provide a suitable environment for the growth of diverse species of seaweeds. Some of the important North Bornean seaweed species are Kappaphycus alvarezii, Eucheuma denticulatum, Halymenia durvillaei (Rhodophyta), Caulerpa lentillifera, Caulerpa racemosa (Chlorophyta), Dictyota dichotoma and Sargassum polycystum (Ochrophyta). This review aims to highlight the therapeutic potential of North Bornean seaweeds and their nutraceutical profiling. North Bornean seaweeds have demonstrated anti-inflammatory, antioxidant, antimicrobial, anticancer, cardiovascular protective, neuroprotective, renal protective and hepatic protective potentials. The protective roles of the seaweeds might be due to the presence of a wide variety of nutraceuticals, including phthalic anhydride, 3,4-ethylenedioxythiophene, 2-pentylthiophene, furoic acid (K. alvarezii), eicosapentaenoic acid, palmitoleic acid, fucoxanthin, β-carotene (E. denticulatum), eucalyptol, oleic acid, dodecanal, pentadecane (H. durvillaei), canthaxanthin, oleic acid, pentadecanoic acid, eicosane (C. lentillifera), pseudoephedrine, palmitic acid, monocaprin (C. racemosa), dictyohydroperoxide, squalene, fucosterol, saringosterol (D. dichotoma), and lutein, neophytadiene, cholest-4-en-3-one and cis-vaccenic acid (S. polycystum). Extensive studies on the seaweed isolates are highly recommended to understand their bioactivity and mechanisms of action, while highlighting their commercialization potential.

The design and development of innovative multifunctional wound dressing materials in engineered biomaterials is essential for promoting tissue repair. In this study, nanofibrous wound dressing materials loaded with anti-inflammatory ingredients were manufactured by a promising electrospinning strategy, and their capability for treating diabetic wounds was also investigated. A scaffold blend consisting of an Enteromorpha polysaccharide and polyvinyl alcohol (PVA) was fabricated. The in vitro and in vivo studies confirmed the efficacy of PVA/EPP1 fiber. We found that PVA/EPP1 fiber accelerated the repair of a full-thickness skin wound in diabetic mice. The results suggest that this scaffold could effectively shorten the wound healing time by inhibiting inflammatory activity, which makes it a promising candidate for the treatment of hard-to-heal wounds caused by diabetes.

Fucoidan is a polysaccharide obtained from marine brown algae, with anti-inflammatory, anti-viral, and immune-enhancing properties, thus, fucoidan may be used as an alternative treatment (complementary to prescribed medical therapy) for COVID-19 recovery. This work aimed to determine the ex-vivo effects of treatment with fucoidan (20 µg/mL) on mitochondrial membrane potential (ΔΨm, using a cationic cyanine dye, 3,3'-dihexyloxacarbocyanine iodide (DiOC6(3)) on human peripheral blood mononuclear cells (HPBMC) isolated from healthy control (HC) subjects, COVID-19 patients (C-19), and subjects that recently recovered from COVID-19 (R1, 40 ± 13 days after infection). In addition, ex-vivo treatment with fucoidan (20 and 50 µg/mL) was evaluated on ΔΨm loss induced by carbonyl cyanide 3-chlorophenylhydrazone (CCCP, 150 µM) in HPBMC isolated from healthy subjects (H) and recovered subjects at 11 months post-COVID-19 (R2, 335 ± 20 days after infection). Data indicate that SARS-CoV-2 infection induces HPBMC loss of ΔΨm, even 11 months after infection, however, fucoidan promotes recovery of ΔΨm in PBMCs from COVID-19 recovered subjects. Therefore, fucoidan may be a potential treatment to diminish long-term sequelae from COVID-19, using mitochondria as a therapeutic target for the recovery of cellular homeostasis.

Enzymatic hydrolysates from Oysters (OAH) display multiple biological activities. Previously, a 3~5 KDa oyster ultrafiltration component (OUP) showed a high property of preventing skin oxidation. Subsequently, we identified specific peptides with such activity. OUP was fractionated stepwise by Sephadex-G25 and RP-HPLC, and active fractions were screened using UV-irradiated HaCaT cells. The most active fractions (OP5-3) were analyzed by LC-MS/MS and a total of 17 peptides were identified. Results from mass spectrometry showed that OP5-3 consisted of peptides with a molecular weight range of 841.51-1786.92 Da. Six of these peptides were synthesized for validating the activity of resisting skin oxidation in the same cell model. All six peptides showed varying degrees of antioxidant activity, while pretreatment of HaCaT cells with AIVAEVNEAAK alleviated UV cytotoxicity, inhibited metalloproteinase 1 (MMP-1) expression, and showed the highest activity to resist UV-induced skin photo-oxidation among these peptides. In addition, results from molecular docking analysis of MMP-1 with AIVAEVNEAAK showed that AIVAEVNEAAK suppresses its enzymatic activity by directly interacting with MMP-1 and thus exhibit anti-photoaging activity.

The current tuberculosis treatment regimen is long and complex, and its failure leads to relapse and emergence of drug resistance. One of the major reasons underlying the extended chemotherapeutic regimen is the ability of Mycobacterium tuberculosis to attain a dormant state. Therefore, the identification of new lead compounds with chemical structures different from those of conventional anti-tuberculosis drugs is essential. The compound 3-(phenethylamino)demethyl(oxy)aaptamine (PDOA, 1), isolated from marine sponge of Aaptos sp., is known as an anti-dormant mycobacterial substance, and has been reported to be effective against the drug resistant strains of M. tuberculosis. However, its target protein still remains unclear. This study aims to clarify the structure-activity relationship of 1 using 15 synthetic analogues, in order to prepare a probe molecule for detecting the target protein of 1. We succeeded in creating the compound 15 with a photoaffinity group that retained antimicrobial activity, which proved to be a suitable probe molecule for identifying the target protein of 1.

As a continuation of our research on the chemical reactivity, pharmacokinetics and ADMET properties of cyclopeptides of marine origin with potential therapeutic abilities, in this work our already presented integrated molecular modeling protocol has been used for the study of the chemical reactivity and bioactivity properties of the Veraguamides A-G family of marine natural drugs. This protocol results from the estimation of the conceptual density functional theory (CDFT) chemical reactivity descriptors together with several chemoinformatics tools commonly considered within the process of development of new therapeutic drugs. CP-CDFT is a branch of computational chemistry and molecular modeling dedicated to the study of peptides, and it is a protocol that allows the estimation with great accuracy of the CDFT-based reactivity descriptors and the associated physical and chemical properties, which can aid in determining the ability of the studied peptides to behave as potential useful drugs. Moreover, the superiority of the MN12SX density functional over other long-range corrected density functionals for the prediction of chemical and physical properties in the presence of water as the solvent is clearly demonstrated. The research was supplemented with an investigation of the bioactivity of the molecular systems and their ADMET (absorption, distribution, metabolism, excretion, and toxicity) parameters, as is customary in medicinal chemistry. Some instances of the CDFT-based chemical reactivity descriptors' capacity to predict the pKas of peptides as well as their potential as AGE inhibitors are also shown.

Chitosan oligosaccharides (COS) have been shown to have potential protective effects against colitis, but the mechanism underlying this effect has not been fully elucidated. In this study, COS were found to significantly attenuate dextran sodium sulfate-induced colitis in mice by decreasing disease activity index scores, downregulating pro-inflammatory cytokines, and upregulating Mucin-2 levels. COS also significantly inhibited the levels of nitric oxide (NO) and IL-6 in lipopolysaccharide-stimulated RAW 264.7 cells. Importantly, COS inhibited the activation of the NF-κB signaling pathway via activating PPARγ and SIRT1, thus reducing the production of NO and IL-6. The antagonist of PPARγ could abolish the anti-inflammatory effects of COS in LPS-treated cells. COS also activated SIRT1 to reduce the acetylation of p65 protein at lysine 310, which was reversed by silencing SIRT1 by siRNA. Moreover, COS treatment increased the diversity of intestinal microbiota and partly restored the Firmicutes/Bacteroidetes ratio. COS administration could optimize intestinal microbiota composition by increasing the abundance of norank_f_Muribaculaceae, Lactobacillus and Alistipes, while decreasing the abundance of Turicibacte. Furthermore, COS could also increase the levels of propionate and butyrate. Overall, COS can improve colitis by regulating intestinal microbiota and the PPARγ/SIRT1-mediated NF-κB pathway.

This study aimed to investigate the influence of kappa (κ)-carrageenan on the initial stages of the foreign body response against pectin gel. Pectin-carrageenan (P-Car) gel beads were prepared from the apple pectin and κ-carrageenan using gelling with calcium ions. The inclusion of 0.5% κ-carrageenan (Car0.5) in the 1.5 (P1.5) and 2% pectin (P2) gel formulations decreased the gel strength by 2.5 times. Car0.5 was found to increase the swelling of P2 gel beads in the cell culture medium. P2 gel beads adsorbed 30-42 mg/g of bovine serum albumin (BSA) depending on pH. P2-Car0.2, P2-Car0.5, and P1.5-Car0.5 beads reduced BSA adsorption by 3.1, 5.2, and 4.0 times compared to P2 beads, respectively, at pH 7. The P1.5-Car0.5 beads activated complement and induced the haemolysis less than gel beads of pure pectin. Moreover, P1.5-Car0.5 gel beads allowed less adhesion of mouse peritoneal macrophages, TNF-α production, and NF-κB activation than the pure pectin gel beads. There were no differences in TLR4 and ICAM-1 levels in macrophages treated with P and P-Car gel beads. P2-Car0.5 hydrogel demonstrated lower adhesion to serous membrane than P2 hydrogel. Thus, the data obtained indicate that the inclusion of κ-carrageenan in the apple pectin gel improves its biocompatibility.

Bacteria growing inside biofilms are more resistant to hostile environments, conventional antibiotics, and mechanical stresses than their planktonic counterparts. It is estimated that more than 80% of microbial infections in human patients are biofilm-based, and biofouling induced by the biofilms of some bacteria causes serious ecological and economic problems throughout the world. Therefore, exploring highly effective anti-biofilm compounds has become an urgent demand for the medical and marine industries. Marine microorganisms, a well-documented and prolific source of natural products, provide an array of structurally distinct secondary metabolites with diverse biological activities. However, up to date, only a handful of anti-biofilm natural products derived from marine microorganisms have been reported. Meanwhile, it is worth noting that some promising antifouling (AF) compounds from marine microbes, particularly those that inhibit settlement of fouling invertebrate larvae and algal spores, can be considered as potential anti-biofilm agents owing to the well-known knowledge of the correlations between biofilm formation and the biofouling process of fouling organisms. In this review, a total of 112 anti-biofilm, anti-larval, and anti-algal natural products from marine microbes and 26 of their synthetic analogues are highlighted from 2000 to 2021. These compounds are introduced based on their microbial origins, and then categorized into the following different structural groups: fatty acids, butenolides, terpenoids, steroids, phenols, phenyl ethers, polyketides, alkaloids, flavonoids, amines, nucleosides, and peptides. The preliminary structure-activity relationships (SAR) of some important compounds are also briefly discussed. Finally, current challenges and future research perspectives are proposed based on opinions from many previous reviews.

Aeruginosamides (AEGs) are classified as cyanobactins, ribosomally synthesized peptides with post-translational modifications. They have been identified in cyanobacteria of genera Microcystis, Oscillatoria, and Limnoraphis. In this work, the new data on the in vitro activities of three AEG variants, AEG A, AEG625 and AEG657, and their interactions with metabolic enzymes are reported. Two aeruginosamides, AEG625 and AEG657, decreased the viability of human breast cancer cell line T47D, but neither of the peptides was active against human liver cancer cell line Huh7. AEGs also did not change the expression of MIR92b-3p, but for AEG625, the induction of oxidative stress was observed. In the presence of a liver S9 fraction containing microsomal and cytosolic enzymes, AEG625 and AEG657 showed high stability. In the same assays, quick removal of AEG A was recorded. The peptides had mild activity against three cytochrome P450 enzymes, CYP2C9, CYP2D6 and CYP3A4, but only at the highest concentration used in the study (60 µM). The properties of AEGs, i.e., cytotoxic activity and in vitro interactions with important metabolic enzymes, form a good basis for further studies on their pharmacological potential.

Though the relationship between dietary fiber and physical health has been investigated widely, the use of dietary fiber from marine plants has been investigated relatively rarely. The Saccharina japonica byproducts after the production of algin contain a large amount of insoluble polysaccharide, which will cause a waste of resources if ignored. Soluble dietary fiber (SDF)prepared from waste byproducts of Saccharina japonica by alkaline hydrolysis method for the first time had a wrinkled microscopic surface and low crystallinity, which not only significantly reduced liver index, serum levels of aspartate aminotransferase (AST) and alanine amiotransferase (ALT), and liver fat accumulation damage to the livers of obese diabetic mice, but also activated the PI3K/AKT signaling pathway to increase liver glycogen synthesis and glycolysis. By LC-MS/MS employing a Nexera UPLC tandem QE high-resolution mass spectrometer, the 6 potential biomarker metabolites were screened, namely glycerophosphocholine (GPC), phosphocholine (PCho), pantothenic acid, glutathione (GSH), oxidized glutathione (GSSG), and betaine; several pathways of these metabolites were associated with lipid metabolism, glycogen metabolism, and amino acid metabolism in the liver were observed. This study further provided a detailed insight into the mechanisms of SDF from Saccharina japonica byproducts in regulating the livers of obese mice with type 2 diabetes and laid a reliable foundation for the further development and utilization of Saccharina japonica.

The organization of bacteria in biofilms is one of the adaptive resistance mechanisms providing increased protection against conventional treatments. Thus, the search for new antibiofilm agents for medical purposes, especially of natural origin, is currently the object of much attention. The objective of the study presented here was to explore the potential of extracts derived from three seaweeds: the green Ulva lactuca, the brown Stypocaulon scoparium, and the red Pterocladiella capillacea, in terms of their antibiofilm activity against P. aeruginosa. After preparation of extracts by successive maceration in various solvents, their antibiofilm activity was evaluated on biofilm formation and on mature biofilms. Their inhibition and eradication abilities were determined using two complementary methods: crystal violet staining and quantification of adherent bacteria. The effect of active extracts on biofilm morphology was also investigated by epifluorescence microscopy. Results revealed a promising antibiofilm activity of two extracts (cyclohexane and ethyl acetate) derived from the green alga by exhibiting a distinct mechanism of action, which was supported by microscopic analyses. The ethyl acetate extract was further explored for its interaction with tobramycin and colistin. Interestingly, this extract showed a promising synergistic effect with tobramycin. First analyses of the chemical composition of extracts by GC-MS allowed for the identification of several molecules. Their implication in the interesting antibiofilm activity is discussed. These findings suggest the ability of the green alga U. lactuca to offer a promising source of bioactive candidates that could have both a preventive and a curative effect in the treatment of biofilms.

Exopolysaccharides (EPSs) are carbohydrate polymers produced and secreted by microorganisms. In a changing marine environment, EPS secretion can reduce damage from external environmental disturbances to microorganisms. Meanwhile, EPSs have promising application prospects in the fields of food, cosmetics, and pharmaceuticals. Changes in external environmental pH have been shown to affect the synthesis of EPSs in microorganisms. In this study, we analyzed the effects of different initial fermentation pHs on the production, monosaccharide composition, and antioxidant activity of the EPSs of Pseudoalteromonas agarivorans Hao 2018. In addition, the transcriptome sequence of P. agarivorans Hao 2018 under different initial fermentation pH levels was determined. GO and KEGG analyses showed that the differentially expressed genes were concentrated in the two-component regulatory system and bacterial chemotaxis pathways. We further identified the expression of key genes involved in EPS synthesis during pH changes. In particular, the expression of genes encoding the glucose/galactose MFS transporter, phosphomannomutase, and mannose-1-phosphate guanylyltransferase was upregulated when the environmental pH increased, thus promoting EPS synthesis. This study not only contributes to elucidating the environmental adaptation mechanisms of P. agarivorans, but also provides important theoretical guidance for the directed development of new products using biologically active polysaccharides.

In many African countries, the Bayoud is a common disease spread involving the fungus Fusarium oxusporum f. sp. albedinis (Foa). The induction of plant natural defenses through the use of seaweed polysaccharides to help plants against pathogens is currently a biological and ecological approach that is gaining more and more importance. In the present study, we used alginate, a natural polysaccharide extracted from a brown algae Bifurcaria bifurcata, to activate date palm defenses, which involve phenylalanine ammonia-lyase (PAL), a key enzyme of phenylpropanoid metabolism. The results obtained showed that at low concentration (1 g·L-1), alginate stimulated PAL activity in date palm roots 5 times more compared to the negative control (water-treated) after 24 h following treatment and 2.5 times more compared to the laminarin used as a positive stimulator of plant natural defenses (positive control of induction). Using qRT-PCR, the expression of a selection of genes involved in three different levels of defense mechanisms known to be involved in response to biotic stresses were investigated. The results showed that, generally, the PAL gene tested and the genes encoding enzymes involved in early oxidative events (SOD and LOX) were overexpressed in the alginate-treated plants compared to their levels in the positive and negative controls. POD and PR protein genes selected encoding β-(1,3)-glucanases and chitinases in this study did not show any significant difference between treatments; suggesting that other genes encoding POD and PR proteins that were not selected may be involved. After 17 weeks following the inoculation of the plants with the pathogen Foa, treatment with alginate reduced the mortality rate by up to 80% compared to the rate in control plants (non-elicited) and plants pretreated with laminarin, which agrees with the induction of defense gene expression and the stimulation of natural defenses in date palm with alginate after 24 h. These results open promising prospects for the use of alginate in agriculture as an inducer that triggers immunity of plants against telluric pathogens in general and of date palm against Fusarium oxysporum f. sp. albedinis in particular.

This study aimed to investigate the protective effect of the metabolites produced by a new Lactiplantibacillus plantarum strain BF1-13, isolated from deep seawater (DSW), on the intestinal epithelial barrier against the dysfunction induced by hydrogen peroxide (H2O2) and to elucidate the mechanism underlying the effect. Protective effect of the metabolites by strain BF1-13 on the barrier function of the intestinal epithelial model treated with H2O2 was investigated by the transepithelial electrical resistance (TEER). The metabolites enhanced the Claudin-4 (CLDN-4) expression, including at the transcription level, indicated by immunofluorescence staining and quantitative RT-PCR. The metabolites also showed a suppression of aquaporin3 (AQP3) expression. Lactic acid (LA) produced by this strain of homofermentative lactic acid bacteria (LAB) had a similar enhancement on CLDN-4 expression. The metabolites of L. plantarum strain BF1-13 alleviated the dysfunction of intestinal epithelial barrier owing to its enhancement on the tight junctions (TJs) by LA, along with its suppression on AQP3-facilitating H2O2 intracellular invasion into Caco-2 cells. This is the first report on the enhancement of TJs by LA produced by LAB.

Cardiovascular diseases (CVDs) have emerged as a major threat to global health resulting in a decrease in life expectancy with respect to humans. Thrombosis is one of the foremost causes of CVDs, and it is characterized by the unwanted formation of fibrin clots. Recently, microbial fibrinolytic enzymes due to their specific features have gained much more attention than conventional thrombolytic agents for the treatment of thrombosis. Marine microorganisms including bacteria and microalgae have the significant ability to produce fibrinolytic enzymes with improved pharmacological properties and lesser side effects and, hence, are considered as prospective candidates for large scale production of these enzymes. There are no studies that have evaluated the fibrinolytic potential of marine fungal-derived enzymes. The current review presents an outline regarding isolation sources, production, features, and thrombolytic potential of fibrinolytic biocatalysts from marine microorganisms identified so far.

Nowadays, the use of marine by-products as precursor materials has gained great interest in the extraction and production of chemical compounds with suitable properties and possible pharmaceutical applications. The present paper presents the development of a new immediate release tablet containing calcium lactate obtained from Black Sea mussel shells. Compared with other calcium salts, calcium lactate has good solubility and bioavailability. In the pharmaceutical preparations, calcium lactate was extensively utilized as a calcium source for preventing and treating calcium deficiencies. The physical and chemical characteristics of synthesized calcium lactate were evaluated using Fourier Transform Infrared Spectroscopy, X-ray diffraction analysis and thermal analysis. Further, the various pharmacotechnical properties of the calcium lactate obtained from mussel shells were determined in comparison with an industrial used direct compressible Calcium lactate DC (PURACAL®). The obtained results suggest that mussel shell by-products are suitable for the development of chemical compounds with potential applications in the pharmaceutical domain.

N-2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC), a cationic quaternary ammonium salt polymer exhibiting good solubility in water, is widely used because of its low toxicity and good biocompatibility. Herein, through ion exchange reaction, we prepared N-2-hydroxypropyltrimethyl ammonium chitosan derivatives bearing amino acid Schiff bases with good biological activities. The accuracy of the structures was verified by FT-IR and 1H NMR. The antibacterial activity, antifungal activity, and scavenging ability of DPPH radical and superoxide radical of HACC derivatives were significantly improved compared with that of HACC. In particular, HACGM (HACC-potassium 2-((2-hydroxy-3-methoxybenzylidene)amino)acetate) and HACGB (HACC-potassium 2-((5-bromo-2-hydroxybenzylidene)amino)acetate) showed good inhibitory effect on bacteria and fungi, including Staphylococcus aureus, Escherichia coli, Botrytis cinerea, and Fusarium oxysporum f. sp. cubense. The inhibition rate of HACGB on Staphylococcus aureus and Escherichia coli could reach 100% at the concentration of 0.1 mg/mL, and the inhibition rate of HACGM and HACGB on Botrytis cinerea and Fusarium oxysporum f. sp. cubense could also reach 100% at the concentration of 0.5 mg/mL. Improving antimicrobial and antioxidant activities of HACC could provide ideas and experiences for the development and utilization of chitosan derivatives.

Quorum sensing (QS) can regulate the pathogenicity of bacteria and the production of some virulence factors. It is a promising target for screening to find anti-virulence agents in the coming post-antibiotics era. Cyclo (L-Trp-L-Ser), one variety of cyclic dipeptides (CDPs), isolated from a marine bacterium Rheinheimera aquimaris, exhibited anti-QS activity against Chromobacterium violaceum CV026 and Pseudomonas aeruginosa PAO1. Unlike the CDPs composed of phenylalanine or tyrosine, the anti-QS activity has been widely studied; however, cyclo (L-Trp-L-Ser) and derivatives, containing one tryptophan unit and one non-aromatic amino acid, have not been systematically explored. Herein, the cyclo (L-Trp-L-Ser) and seven derivatives were synthesized and evaluated. All tryptophane-contained CDPs were able to decrease the production of violacein in C.violaceum CV026 and predicted as binding within the same pocket of receptor protein CviR, but in lower binding energy compared with the natural ligand C6HSL. As for P. aeruginosa PAO1, owning more complicated QS systems, these CDPs also exhibited inhibitory effects on pyocyanin production, swimming motility, biofilm formation, and adhesion. These investigations suggested a promising way to keep the tryptophan untouched and make modifications on the non-aromatic unit to increase the anti-QS activity and decrease the cytotoxicity, thus developing a novel CDP-based anti-virulence agent.

Marine microorganisms have proven to be a source of new natural products with a wide spectrum of biological activities relevant in different industrial sectors. The ever-increasing number of sequenced microbial genomes has highlighted a discrepancy between the number of gene clusters potentially encoding the production of natural products and the actual number of chemically characterized metabolites for a given microorganism. Homologous and heterologous expression of these biosynthetic genes, which are often silent under experimental laboratory culture conditions, may lead to the discovery of new cryptic natural products of medical and biotechnological interest. Several new genetic and cultivation-based strategies have been developed to meet this challenge. The OSMAC approach (one strain-many compounds), based on modification of growth conditions, has proven to be a powerful strategy for the discovery of new cryptic natural products. As a direct extension of this approach, the addition of chemical elicitors or epigenetic modifiers have also been used to activate silent genes. This review looks at the structures and biological activities of new cryptic metabolites from marine-derived microorganisms obtained using the OSMAC approach, the addition of chemical elicitors, and enzymatic inhibitors and epigenetic modifiers. It covers works published up to June 2021.

To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2-37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against Helicoverpa armigera Hübner than 1. In particular, 15 showed potent insecticidal activity with an IC50 value of 89 μM, comparable to the positive control azadirachtin (IC50 = 70 μM). Additionally, 5, 12, 13, 16, 30 and 33 showed strong antibacterial activity against Staphylococcus aureus and Aeromonas salmonicida with MIC values in the range of 1.15-4.93 μM. The preliminary structure-activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into 1 and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin.

Palytoxin (PLTX) is a highly toxic polyether identified in various marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. In addition to adverse effects in humans, negative impacts on different marine organisms have been often described during Ostreopsis blooms and the concomitant presence of PLTX and its analogues. Considering the increasing frequency of Ostreopsis blooms due to global warming, PLTX was investigated for its effects on Artemia franciscana, a crustacean commonly used as a model organism for ecotoxicological studies. At concentrations comparable to those detected in culture media of O. cf. ovata (1.0-10.0 nM), PLTX significantly reduced cysts hatching and induced significant mortality of the organisms, both at larval and adult stages. Adults appeared to be the most sensitive developmental stage to PLTX: significant mortality was recorded after only 12 h of exposure to PLTX concentrations > 1.0 nM, with a 50% lethal concentration (LC50) of 2.3 nM (95% confidence interval = 1.2-4.7 nM). The toxic effects of PLTX toward A. franciscana adults seem to involve oxidative stress induction. Indeed, the toxin significantly increased ROS levels and altered the activity of the major antioxidant enzymes, in particular catalase and peroxidase, and marginally glutathione-S-transferase and superoxide dismutase. On the whole, these results indicate that environmentally relevant concentrations of PLTX could have a negative effect on Artemia franciscana population, suggesting its potential ecotoxicological impact at the marine level.

Streptomyces sp. GET02.ST and Achromobacter sp. GET02.AC were isolated together from the gut of the wharf roach, Ligia&nbsp;exotica, inhabiting the intertidal zone of the west coast of Korea. The co-cultivation of these two strains significantly induced the production of two new metabolites, ligiamycins A (1) and B (2), which were barely detected in the single culture of Streptomyces sp. GET02.ST. The planar structures of ligiamycins A (1) and B (2) were elucidated as new decalins coupled with amino-maleimides by the analysis of various spectroscopic data, including nuclear magnetic resonance (NMR), ultraviolet (UV), and mass (MS) data. The assignment of two nitrogen atoms in amino-maleimide in 1 was accomplished based on 1H-15N heteroatom single quantum coherence spectroscopy (HSQC) NMR experiments. The relative configurations of the ligiamycins were determined using rotating frame Overhauser effect spectroscopy (ROESY) NMR data, and their absolute configurations were deduced by comparing their experimental and calculated optical rotations. Ligiamycin A (1) displayed antibacterial effects against Staphylococcus aureus and Salmonella enterica, while ligiamycin B (2) exhibited mild cell cytotoxicity against human colorectal cancer cells.

Eight trichothecenes, including four new compounds 1-4 and four known entities 5-8, together with one known cyclonerane (9) were isolated from the solid-state fermentation of Trichoderma&nbsp;brevicompactum NTU439 isolated from the marine alga Mastophora rosea. The structures of 1-9 were determined by 1D/2D NMR (nuclear magnetic resonance), MS (mass spectrometry), and IR (infrared spectroscopy) spectroscopic data. All of the compounds were evaluated for cytotoxic activity against HCT-116, PC-3, and SK-Hep-1 cancer cells by the SRB assay, and compound 8 showed promising cytotoxic activity against all three cancer cell lines with the IC50 values of 3.3 ± 0.3, 5.3 ± 0.3, and 1.8 ± 0.8 μM, respectively. Compounds 1-2, 4-6, and 7-8 potently inhibited LPS-induced NO production, and compounds 5 and 8 showed markedly inhibited gelatinolysis of MMP-9 in S1 protein-stimulated THP-1 monocytes.

Seven new compounds, namely talaromanloid A (1), talaromydene (2), 10-hydroxy-8-demethyltalaromydine and 11-hydroxy-8-demethyltalaromydine (3 and 4), talaromylectone (5), and ditalaromylectones A and B (6 and 7), together with seven known compounds were identified from a marine-derived fungus, Talaromyces mangshanicus BTBU20211089, which was isolated from a sediment sample collected from the South China Sea. Their chemical structures were determined using spectroscopic data, including HRESIMS, 1D, and 2D NMR techniques. The absolute configurations of 1 and 2 were elucidated by comparing experimental and calculated ECD spectra. Compounds 1, 2, 6, and 7 are new compounds possessing a novel carbon skeleton. Compound 6 is a dimeric molecule of 3 and 9. Compound 7 shared a unique structure of the cyclized dimer of 3 and 4. All the compounds were tested for their bioactivities against Staphylococcus aureus, Escherichia coli, and Candida albicans.

Three new tripeptide derivatives asterripeptides A-C (1-3) were isolated from Vietnamese mangrove-derived fungus Aspergillus terreus LM.5.2. Structures of isolated compounds were determined by a combination of NMR and ESIMS techniques. The absolute configurations of all stereocenters were determined using the Murfey's method. The isolated compounds 1-3 contain a rare fungi cinnamic acid residue. The cytotoxicity of isolated compounds against several cancer cell lines and inhibition ability of sortase A from Staphylococcus aureus of asterripeptides A-C were investigated.

Puniceusines A-N (1-14), 14 new isoquinoline alkaloids, were isolated from the extracts of a deep-sea-derived fungus, Aspergillus puniceus SCSIO z021. Their structures were elucidated by spectroscopic analyses. The absolute configuration of 9 was determined by ECD calculations, and the structures of 6 and 12 were further confirmed by a single-crystal X-ray diffraction analysis. Compounds 3-5 and 8-13 unprecedentedly contained an isoquinolinyl, a polysubstituted benzyl or a pyronyl at position C-7 of isoquinoline nucleus. Compounds 3 and 4 showed selective inhibitory activity against protein tyrosine phosphatase CD45 with IC50 values of 8.4 and 5.6 µM, respectively, 4 also had a moderate cytotoxicity towards human lung adenocarcinoma cell line H1975 with an IC50 value of 11.0 µM, and 14, which contained an active center, -C=N+, exhibited antibacterial activity. An analysis of the relationship between the structures, enzyme inhibitory activity and cytotoxicity of 1-14 revealed that the substituents at C-7 of the isoquinoline nucleus could greatly affect their bioactivity.

FGFC1, an active compound isolated from the culture of marine fungi Stachybotrys longispora FG216, elicits fibrinolytic, anti-oxidative, and anti-inflammatory activity. We have previously reported that FGFC1 inhibited the proliferation, migration, and invasion of the non-small cell lung cancer (NSCLC) cells in vitro. However, the precise mechanisms of FGFC1 on NSCLC and its anti-cancer activity in vivo remains unclear. Hence, this study was focused to investigate the effects and regulatory mechanisms of FGFC1 on two NSCLC cell lines, EGFR-mutant PC9 (ex19del) and EGFR wild-type H1299. Results suggested that FGFC1 significantly inhibited proliferation, colony formation, as well as triggered G0/G1 arrest and apoptosis of PC9 cells in a dose- and time-dependent manner, but no obvious inhibitory effects were observed in H1299 cells. Subsequently, transcriptome analysis revealed that FGFC1 significantly down-regulated 28 genes related to the NF-κB pathway, including IL-6, TNF-α, and ICAM-1 in the PC9 cells. We further confirmed that FGFC1 decreased the expression of protein p-IKKα/β, p-p65, p-IκB, IL-6, and TNF-α. Moreover, NF-κB inhibitor PDTC could strengthen the effects of FGFC1 on the expression of CDK4, Cyclin D1, cleaved-PARP-1, and cleaved-caspase-3 proteins, suggesting that the NF-κB pathway plays a major role in FGFC1-induced cell cycle arrest and apoptosis. Correspondingly, the nuclear translocation of p-p65 was also suppressed by FGFC1 in PC9 cells. Finally, the intraperitoneal injection of FGFC1 remarkably inhibited PC9 xenograft growth and decreased the expression of Ki-67, p-p65, IL-6, and TNF-α in tumors. Our results indicated that FGFC1 exerted anti-cancer activity in PC9 cells via inhibiting the NF-κB signaling pathway, providing a possibility for FGFC1 to be used as a lead compound for the treatment of NSCLC in the future.

Actinoporins are proteinaceous toxins known for their ability to bind to and create pores in cellular membranes. This quality has generated interest in their potential use as new tools, such as therapeutic immunotoxins. Isolated historically from sea anemones, genes encoding for similar actinoporin-like proteins have since been found in a small number of other animal phyla. Sequencing and de novo assembly of Irish Haliclona transcriptomes indicated that sponges also possess similar genes. An exhaustive analysis of publicly available sequencing data from other sponges showed that this is a potentially widespread feature of the Porifera. While many sponge proteins possess a sequence similarity of 27.70-59.06% to actinoporins, they show consistency in predicted structure. One gene copy from H. indistincta has significant sequence similarity to sea anemone actinoporins and possesses conserved residues associated with the fundamental roles of sphingomyelin recognition, membrane attachment, oligomerization, and pore formation, indicating that it may be an actinoporin. Phylogenetic analyses indicate frequent gene duplication, no distinct clade for sponge-derived proteins, and a stronger signal towards actinoporins than similar proteins from other phyla. Overall, this study provides evidence that a diverse array of Porifera represents a novel source of actinoporin-like proteins which may have biotechnological and pharmaceutical applications.

The incidence of neurodegenerative diseases, such as Alzheimer's disease (AD), increases continuously demanding the urgent development of anti-Alzheimer's agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, such as akaloids, to defend themselves. Therefore, the identification of marine natural products with neuroprotective effects is a necessity. Being that AD is not only a genetic but also an environmental complex disease, a treatment for AD remains to discover. As the major clinical indications (CI) of AD are extracellular plaques formed by β-amyloid (Aβ) protein, intracellular neurofibrillary tangles (NFTs) formed by hyper phosphorylated τ-protein, uncommon inflammatory response and neuron apoptosis and death caused by oxidative stress, alkaloids that may decrease CI, might be used against AD. Most of the alkalolids with those properties are derivatives of the amino acid tryptophan mainly with a planar indole scaffold. Certainly, alkaloids targeting more than one CI, multitarget-directed ligands (MTDL), have the potential to become a lead in AD treatment. Alkaloids to have a maximum of activity against CI, should be planar and contain halogens and amine quaternization.

Xanthophylls, a yellow pigment belonging to the carotenoid family, have attracted much attention for industrial applications due to their versatile nature. We report the isolation of a homo xanthophyll pigment-producing marine bacterium, identified as the Erythrobacter sp. SDW2 strain, from coastal seawater. The isolated Erythrobacter sp. SDW2 strain can produce 263 ± 12.9 mg/L (89.7 ± 5.4 mg/g dry cell weight) of yellow xanthophyll pigment from 5 g/L of glucose. Moreover, the xanthophyll pigment produced by the SDW2 strain exhibits remarkable antioxidative activities, confirmed by the DPPH (73.4 ± 1.4%) and ABTS (84.9 ± 0.7%) assays. These results suggest that the yellow xanthophyll pigment-producing Erythrobacter sp. SDW2 strain could be a promising industrial microorganism for producing marine-derived bioactive compounds with potential for foods, cosmetics, and pharmaceuticals.

Six new α-pyrone meroterpenoid chevalones H-M (1-6), together with six known compounds (7-12), were isolated from the gorgonian coral-derived fungus Aspergillus hiratsukae SCSIO 7S2001 collected from Mischief Reef in the South China Sea. Their structures, including absolute configurations, were elucidated on the basis of spectroscopic analysis and X-ray diffraction data. Compounds 1-5 and 7 showed different degrees of antibacterial activity with MIC values of 6.25-100 μg/mL. Compound 8 exhibited potent cytotoxicity against SF-268, MCF-7, and A549 cell lines with IC50 values of 12.75, 9.29, and 20.11 μM, respectively.

Marine myxobacteria present a virtually unexploited reservoir for the discovery of natural products with diverse biological functions and novel chemical scaffolds. We report here the isolation and structure elucidation of eight new deoxyenhygrolides (1-8) from the marine myxobacterium Plesiocystis pacifica DSM 14875T. The herein described deoxyenhygrolides C-J (1-8) feature a butenolide core with an ethyl residue at C-3 of the γ-lactone in contrast to the previously described derivatives, deoxyenhygrolides A and B, which feature an isobutyl residue at this position. The butenolide core is 2,4-substituted with a benzyl (1, 2 and 7), benzoyl (3 and 4) or benzyl alcohol (5, 6 and 8) moiety in the 2-position and a benzylidene (1-6) or benzylic hemiketal (7 and 8) in the 4-position. The description of these new deoxyenhygrolide derivatives, alongside genomic in silico investigation regarding putative biosynthetic genes, provides some new puzzle pieces on how this natural product class might be formed by marine myxobacteria.

Japanese Spanish mackerel (JSM) (Scomberomorus niphonius) is a marine fish species containing health-beneficial polyunsaturated fatty acids (PUFAs). In the present study, the quality of JSM by-products oils extracted by supercritical CO2 (SC-CO2) and organic solvent extraction was compared in terms of physico-chemical properties of the oils. Eicosapentaenoic acid (EPA) is one of the important polyunsaturated fatty acids present in SC-CO2-extracted skin and muscle oil 5.81 ± 0.69% and 4.93 ± 0.06%, respectively. The amount of docosahexaenoic acid (DHA) in SC-CO2-extracted skin and muscle oil was 12.56 ± 0.38% and 15.01 ± 0.28%, respectively. EPA and DHA are considered as important PUFAs for the development of brain function and the prevention of coronary heart diseases. Extracted oils showed considerable antioxidant activity. In the obtained oils, atherogenic index (AI) values varied from 0.72 to 0.93 and thrombogenic index (TI) ranged from 0.75 to 0.92, which is considered an acceptable level. Fatty acid composition, bio potentiality, thermogravimetric, and vitamin D analysis showed that oils extracted from JSM by-products can be a good source of oil for application in food, pharmaceutical and cosmetic industries. Therefore, the present research revealed the potentiality of green valorisation of S. niphonius by-products as a possible sustainable approach for targeting the era of zero waste.

Chitosan obtained from abundant marine resources has been proven to have a variety of biological activities. However, due to its poor water solubility, chitosan application is limited, and the degradation products of chitosan oligosaccharides are better than chitosan regarding performance. Chitosan oligosaccharides have two kinds of active groups, amino and hydroxyl groups, which can form a variety of derivatives, and the properties of these derivatives can be further improved. In this review, the key structures of chitosan oligosaccharides and recent studies on chitosan oligosaccharide derivatives, including their synthesis methods, are described. Finally, the antimicrobial and antitumor applications of chitosan oligosaccharides and their derivatives are discussed.

Crypthecodinium cohnii is a marine heterotrophic dinoflagellate that can accumulate high amounts of omega-3 polyunsaturated fatty acids (PUFAs), and thus has the potential to replace conventional PUFAs production with eco-friendlier technology. So far, C. cohnii cultivation has been mainly carried out with the use of yeast extract (YE) as a nitrogen source. In the present study, alternative carbon and nitrogen sources were studied: the extraction ethanol (EE), remaining after lipid extraction, as a carbon source, and dinoflagellate extract (DE) from recycled algae biomass C. cohnii as a source of carbon, nitrogen, and vitamins. In mediums with glucose and DE, the highest specific biomass growth rate reached a maximum of 1.012 h-1, while the biomass yield from substrate reached 0.601 g·g-1. EE as the carbon source, in comparison to pure ethanol, showed good results in terms of stimulating the biomass growth rate (an 18.5% increase in specific biomass growth rate was observed). DE supplement to the EE-based mediums promoted both the biomass growth (the specific growth rate reached 0.701 h-1) and yield from the substrate (0.234 g·g-1). The FTIR spectroscopy data showed that mediums supplemented with EE or DE promoted the accumulation of PUFAs/docosahexaenoic acid (DHA), when compared to mediums containing glucose and commercial YE.

Colorectal cancer is one of the most common cancers diagnosed in the world. Chemotheraphy is one of the most common methods used for the pharmacological treatment of this cancer patients. Nevertheless, the adverse effect of chemotherapy is not optimized for improving the quality of life of people who are older, who are the most vulnerable subpopulation. This review presents recent updates regarding secondary metabolites derived from marine fungi and actinobacteria as novel alternatives for cytotoxic agents against colorectal cancer cell lines HCT116, HT29, HCT15, RKO, Caco-2, and SW480. The observed marine-derived fungi were from the species Aspergillus sp., Penicillium sp., Neosartorya sp., Dichotomomyces sp., Paradendryphiella sp., and Westerdykella sp. Additionally, Streptomyces sp. and Nocardiopsis sp. are actinobacteria discussed in this study. Seventy one compounds reviewed in this study were grouped on the basis of their chemical structures. Indole alkaloids and diketopiperazines made up most compounds with higher potencies when compared with other groups. The potency of indole alkaloids and diketopiperazines was most probably due to halogen-based functional groups and sulfide groups, respectively.

As a low molecular weight alginate, alginate oligosaccharides (AOS) exhibit improved water solubility, better bioavailability, and comprehensive health benefits. In addition, their biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and gelling capability make them an excellent biomaterial with a dual curative effect when applied in a drug delivery system. In this paper, a novel alginate lyase, Algpt, was cloned and characterized from a marine bacterium, Paenibacillus sp. LJ-23. The purified enzyme was composed of 387 amino acid residues, and had a molecular weight of 42.8 kDa. The optimal pH of Algpt was 7.0 and the optimal temperature was 45 °C. The analysis of the conserved domain and the prediction of the three-dimensional structure indicated that Algpt was a novel alginate lyase. The dominant degradation products of Algpt on alginate were AOS dimer to octamer, depending on the incubation time, which demonstrated that Algpt degraded alginate in an endolytic manner. In addition, Algpt was a salt-independent and thermo-tolerant alginate lyase. Its high stability and wide adaptability endow Algpt with great application potential for the efficient preparation of AOS with different sizes and AOS-based products.

The underexplored biodiversity of seaweeds has recently drawn great attention from researchers to find the bioactive compounds that might contribute to the growth of the blue economy. In this study, we aimed to explore the effect of seasonal growth (from May to September) on the in vitro antioxidant (FRAP, DPPH, and ORAC) and antimicrobial effects (MIC and MBC) of Cystoseira compressa collected in the Central Adriatic Sea. Algal compounds were analyzed by UPLC-PDA-ESI-QTOF, and TPC and TTC were determined. Fatty acids, among which oleic acid, palmitoleic acid, and palmitic acid were the dominant compounds in samples. The highest TPC, TTC and FRAP were obtained for June extract, 83.4 ± 4.0 mg GAE/g, 8.8 ± 0.8 mg CE/g and 2.7 ± 0.1 mM TE, respectively. The highest ORAC value of 72.1 ± 1.2 µM TE was obtained for the August samples, and all samples showed extremely high free radical scavenging activity and DPPH inhibition (>80%). The MIC and MBC results showed the best antibacterial activity for the June, July and August samples, when sea temperature was the highest, against Listeria monocytogenes, Staphylococcus aureus, and Salmonella enteritidis. The results show C. compressa as a potential species for the industrial production of nutraceuticals or functional food ingredients.

The chemical investigation of the Mediterranean ascidian Clavelina lepadiformis has led to the isolation of a new lepadin, named lepadin L, and two known metabolites belonging to the same family, lepadins A and B. The planar structure and relative configuration of the decahydroquinoline ring of lepadin L were established both by means of HR-ESIMS and by a detailed as extensive analysis of 1D and 2D NMR spectra. Moreover, microscale derivatization of the new alkaloid lepadin L was performed to assess the relative configuration of the functionalized alkyl side chain. Lepadins A, B, and L were tested for their cytotoxic activity on a panel of cancer cell lines (human melanoma [A375], human breast [MDA-MB-468], human colon adenocarcinoma [HT29], human colorectal carcinoma [HCT116], and mouse myoblast [C2C12]). Interestingly, a deeper investigation into the mechanism of action of the most cytotoxic metabolite, lepadin A, on the A375 cells has highlighted its ability to induce a strongly inhibition of cell migration, G2/M phase cell cycle arrest and a dose-dependent decrease of cell clonogenity, suggesting that it is able to impair self-renewing capacity of A375 cells.

Marine environments are underexplored terrains containing fungi that produce a diversity of natural products given unique environmental pressures and nutrients. While bacteria are commonly the most studied microorganism for natural products in the marine world, marine fungi are also abundant but remain an untapped source of bioactive metabolites. Given that their terrestrial counterparts have been a source of many blockbuster antitumor agents and anti-infectives, including camptothecin, the penicillins, and cyclosporin A, marine fungi also have the potential to produce new chemical scaffolds as leads to potential drugs. Fungi are more phylogenetically diverse than bacteria and have larger genomes that contain many silent biosynthetic gene clusters involved in making bioactive compounds. However, less than 5% of all known fungi have been cultivated under standard laboratory conditions. While the number of reported natural products from marine fungi is steadily increasing, their number is still significantly lower compared to those reported from their bacterial counterparts. Herein, we discuss many varied cytotoxic and anti-infective fungal metabolites isolated from extreme marine environments, including symbiotic associations as well as extreme pressures, temperatures, salinity, and light. We also discuss cultivation strategies that can be used to produce new bioactive metabolites or increase their production. This review presents a large number of reported structures though, at times, only a few of a large number of related structures are shown.

Marine organisms harbor numerous bioactive substances that can be utilized in the pharmaceutical and cosmetic industries. Scientific research on various applications of collagen extracted from these organisms has become increasingly prevalent. Marine collagen can be used as a biomaterial because it is water soluble, metabolically compatible, and highly accessible. Upon review of the literature, it is evident that marine collagen is a versatile compound capable of healing skin injuries of varying severity, as well as delaying the natural human aging process. From in vitro to in vivo experiments, collagen has demonstrated its ability to invoke keratinocyte and fibroblast migration as well as vascularization of the skin. Additionally, marine collagen and derivatives have proven beneficial and useful for both osteoporosis and osteoarthritis prevention and treatment. Other bone-related diseases may also be targeted by collagen, as it is capable of increasing bone mineral density, mineral deposition, and importantly, osteoblast maturation and proliferation. In this review, we demonstrate the advantages of marine collagen over land animal sources and the biomedical applications of marine collagen related to bone and skin damage. Finally, some limitations of marine collagen are briefly discussed.

Different classes of phytochemicals were previously isolated from the Red Sea algae Hypnea&nbsp;musciformis as sterols, ketosteroids, fatty acids, and terpenoids. Herein, we report the isolation of three fatty acids-docosanoic acid 4, hexadecenoic acid 5, and alpha hydroxy octadecanoic acid 6-as well as three ceramides-A (1), B (2), and C (3)-with 9-methyl-sphinga-4,8-dienes and phytosphingosine bases. Additionally, different phytochemicals were determined using the liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (LC-ESI-HRMS) technique. Ceramides A (1) and B (2) exhibited promising in vitro cytotoxic activity against the human breast adenocarcinoma (MCF-7) cell line when compared with doxorubicin as a positive control. Further in vivo study and biochemical estimation in a mouse model of Ehrlich ascites carcinoma (EAC) revealed that both ceramides A (1) and B (2) at doses of 1 and 2 mg/kg, respectively, significantly decreased the tumor size in mice inoculated with EAC cells. The higher dose (2 mg/kg) of ceramide B (2) particularly expressed the most pronounced decrease in serum levels of vascular endothelial growth factor -B (VEGF-B) and tumor necrosis factor-α (TNF-α) markers, as well as the expression levels of the growth factor midkine in tumor tissue relative to the EAC control group. The highest expression of apoptotic factors, p53, Bax, and caspase 3 was observed in the same group that received 2 mg/kg of ceramide B (2). Molecular docking simulations suggested that ceramides A (1) and B (2) could bind in the deep grove between the H2 helix and the Ser240-P250 loop of p53, preventing its interaction with MDM2 and leading to its accumulation. In conclusion, this study reports the cytotoxic, apoptotic, and antiangiogenic effects of ceramides isolated from the Red Sea algae Hypnea&nbsp;musciformis in an experimental model of EAC.

Four new streptoglycerides E-H (1-4), with a rare 6/5/5/-membered ring system, were isolated from a marine-derived actinomycete Streptomyces specialis. The structures of 1-4 were elucidated by detailed analysis of HRESIMS, 1D and 2D NMR data and ECD spectra as well as comparison of their spectroscopic data with those reported in literature. Compounds 1-4 showed significant anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production in Raw 264.7 cells with IC50 values ranging from 3.5 to 10.9 µM. Especially, 2 suppressed mRNA expression levels of iNOS and IL-6 without cytotoxicity.

Chemical investigations of a marine sponge-associated Bacillus revealed six new imidazolium-containing compounds, bacillimidazoles A-F (1-6). Previous reports of related imidazolium-containing natural products are rare. Initially unveiled by timsTOF (trapped ion mobility spectrometry) MS data, extensive HRMS and 1D and 2D NMR analyses enabled the structural elucidation of 1-6. In addition, a plausible biosynthetic pathway to bacillimidazoles is proposed based on isotopic labeling experiments and invokes the highly reactive glycolytic adduct 2,3-butanedione. Combined, the results of structure elucidation efforts, isotopic labeling studies and bioinformatics suggest that 1-6 result from a fascinating intersection of primary and secondary metabolic pathways in Bacillus sp. WMMC1349. Antimicrobial assays revealed that, of 1-6, only compound six displayed discernible antibacterial activity, despite the close structural similarities shared by all six natural products.