Mar. Drugs, Volume 21, Issue 11 (November 2023) – 50 articles

Two new compounds, named rhizoaspergillin A (1) and rhizoaspergillinol A (2), were isolated from the mangrove endophytic fungus Aspergillus sp. A1E3, associated with the fruit of Rhizophora mucronata, together with averufanin (3). The planar structures and absolute configurations of rhizoaspergillinol A (2) and averufanin (3) were established by extensive NMR investigations and quantum-chemical electronic circular dichroism (ECD) calculations. Most notably, the constitution and absolute configuration of rhizoaspergillin A (1) were unambiguously determined by single-crystal X-ray diffraction analysis of its tri-pivaloyl derivative 4, conducted with Cu Kα radiation, whereas those of averufanin (3) were first clarified by quantum-chemical ECD calculations. Rhizoaspergillin A is the first orsellinic acid–ribose–pyridazinone-N-oxide hybrid containing a unique β-oxo-2,3-dihydropyridazine 1-oxide moiety, whereas rhizoaspergillinol A (2) and averufanin (3) are sterigmatocystin and anthraquinone derivatives, respectively. From the perspective of biosynthesis, rhizoaspergillin A (1) could be originated from the combined assembly of three building blocks, viz., orsellinic acid, β-D-ribofuranose, and L-glutamine. It is an unprecedented alkaloid-N-oxide involving biosynthetic pathways of polyketides, pentose, and amino acids. In addition, rhizoaspergillinol A (2) exhibited potent antiproliferative activity against four cancer cell lines. It could dose-dependently induce G2/M phase arrest in HepG2 cells. Full article

Harmful algal blooms (HABs) can produce a variety of noxious effects and, in some cases, the massive mortality of wild and farmed marine organisms. Some HAB species produce toxins that are released into seawater or transferred via food webs (particulate toxin fraction). The objective of the present study was to identify the toxicological effects of subacute exposure to saxitoxin (STX) during embryonic and early larval stages in Seriola rivoliana. Eggs were exposed to dissolved 19 STX (100 μg L⁻¹). The toxic effects of STX were evaluated via the hatching percentage, the activity of three enzymes (protein and alkaline phosphatases and peroxidase), and the expression of four genes (HSF2, Nav1.4b, PPRC1, and DUSP8). A low hatching percentage (less than 5%) was observed in 44 hpf (hours post fertilization) embryos exposed to STX compared to 71% in the unexposed control. At this STX concentration, no oxidative stress in the embryos was evident. However, STX induced the expression of the NaV1.4 channel α-subunit (NaV1.4b), which is the primary target of this toxin. Our results revealed the overexpression of all four candidate genes in STX-intoxicated lecithotrophic larvae, reflecting the activation of diverse cellular processes involved in stress responses (HSF2), lipid metabolism (PPRC1), and MAP kinase signaling pathways associated with cell proliferation and differentiation (DUSP8). The effects of STX were more pronounced in young larvae than in embryos, indicating a stage-specific sensitivity to the toxin. Full article

A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A–C (1–3) and one novel hybrid polyketide hepialide (4), together with 18 known miscellaneous compounds (5–22). The structures of the new compounds were elucidated through detailed spectroscopic analysis. as well as TD-DFT-based ECD calculation. All isolates were tested for anti-inflammatory activity in vitro. Under a concentration of 1 µM, compounds 8, 11, 13, 21, and 22 showed potent inhibitory activity against nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells, with inhibition rates of 34.2%, 30.7%, 32.9%, 38.6%, and 58.2%, respectively. Of particularly note is compound 22, which exhibited the most remarkable inhibitory activity, with an IC₅₀ value of 426.2 nM. Full article

The brown algal genus Fucus provides essential ecosystem services crucial for marine environments. Macroalgae (seaweeds) release dissolved organic matter, hence, are under strong settlement pressure from micro- and macrofoulers. Seaweeds are able to control surface epibionts directly by releasing antimicrobial compounds onto their surfaces, and indirectly by recruiting beneficial microorganisms that produce antimicrobial/antifouling metabolites. In the Kiel Fjord, in the German Baltic Sea, three distinct Fucus species coexist: F. vesiculosus, F. serratus, and F. distichus subsp. evanescens. Despite sharing the same habitat, they show varying fouling levels; F. distichus subsp. evanescens is the least fouled, while F. vesiculosus is the most fouled. The present study explored the surface metabolomes and epiphytic microbiota of these three Fucus spp., aiming to uncover the factors that contribute to the differences in the fouling intensity on their surfaces. Towards this aim, algal surface metabolomes were analyzed using comparative untargeted LC-MS/MS-based metabolomics, to identify the marker metabolites influencing surface fouling. Their epiphytic microbial communities were also comparatively characterized using high-throughput amplicon sequencing, to pinpoint the differences in the surface microbiomes of the algae. Our results show that the surface of the least fouling species, F. distichus subsp. evanescens, is enriched with bioactive compounds, such as betaine lipids MGTA, 4-pyridoxic acid, and ulvaline, which are absent from the other species. Additionally, it exhibits a high abundance of the fungal genera Mucor and Alternaria, along with the bacterial genus Yoonia-Loktanella. These taxa are known for producing antimicrobial/antifouling compounds, suggesting their potential role in the observed fouling resistance on the surface of the F. distichus subsp. evanescens compared to F. serratus and F. vesiculosus. These findings provide valuable clues on the differential surface fouling intensity of Fucus spp., and their importance in marine chemical defense and fouling dynamics. Full article

Nanomaterials (NMs) are becoming more commonly used in microalgal biotechnology to empower the production of algal biomass and valuable metabolites, such as lipids, proteins, and exopolysaccharides. It provides an effective and promising supplement to the existing algal biotechnology. In this review, the potential for NMs to enhance microalgal growth by improving photosynthetic utilization efficiency and removing reactive oxygen species is first summarized. Then, their positive roles in accumulation, bioactivity modification, and extraction of valuable microalgal metabolites are presented. After the application of NMs in microalgae cultivation, the extracted metabolites, particularly exopolysaccharides, contain trace amounts of NM residues, and thus, the impact of these residues on the functional properties of the metabolites is also evaluated. Finally, the methods for removing NM residues from the extracted metabolites are summarized. This review provides insights into the application of nanotechnology for sustainable production of valuable metabolites in microalgae and will contribute useful information for ongoing and future practice. Full article

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents. Full article

Paracetamol or acetaminophen (PAC) is a commonly used analgesic and antipyretic drug. It has been shown that overdoses beyond the therapeutic range can cause hepatotoxicity and acute liver injury. The most common cause of drug-induced liver injury (DILI) in Saudi Arabia and worldwide is paracetamol overdose. Fucoxanthin (FUC) is an allenic carotenoid that is found in edible brown seaweeds, and it has antioxidant and anti-inflammatory effects. Several studies have shown the potential therapeutic effects of FUC in diabetes, cancers, and inflammatory disorders. This study aims to investigate the protective effect of FUC against PAC-induced acute liver injury in rats. FUC was administered (100, 200, and 500 mg/kg, p.o.) for 7 days, and then the liver injury was induced by the administration of PAC (2000 mg/kg, oral). Blood and liver tissue samples were collected from PAC-positive untreated, treated, and negative control rats. Biochemical and inflammatory parameters in the blood were measured. In addition, RT-PCR, Western blotting, and immunohistochemistry were performed for liver tissue. The serum levels of liver biomarkers (ALT, AST, and ALP) increased after PAC-induced liver toxicity; FUC-treated rats showed lower levels compared to the positive control. There was an increase in the expression of TNF-α, IL-1, IL-6, NF-kB, INF-γ, and iNOS and a decrease in IL-10, IL-22, and IL-10R expression after the FUC treatment of injured liver rats. For the hepatic inflammation and PAC-toxicity-induced oxidative stress genes and proteins, FUC-treated rats (100, 200, and 500 mg/kg) showed a reduction in the expression of oxidative stress genes. These results showed that FUC protected the liver against PAC-induced injury through antioxidant and anti-inflammatory actions. However, further clinical studies are required to confirm the findings. Full article

Currently, side-streams (e.g., head, backbone, tail, and intestines) generated in the fish processing industry often end up as low-value products for feed applications or even as waste. In order to upcycle such side-streams, they need to be preserved to avoid oxidative degradation of the lipids between the generation point and the valorization plant. In the cod filleting industry, three main solid side-streams: viscera, heads, and backbones, are obtained. Hence, this study aimed to identify the most efficient antioxidant for preserving the cod side-streams using a dipping-based strategy prior to pre-valorization storage at low temperatures (ice and frozen storage). The dipping solutions evaluated contained: (i) a lipophilic rosemary extract (0.05% and 0.2% in 0.9% NaCl), (ii) Duralox MANC (a mixture of rosemary extract, ascorbic acid, tocopherols, and citric acid; 2% in 0.9% NaCl), and (iii) NaCl (0.9%) w/w solution. One group was not dipped. No dipping and dipping in NaCl were included as controls. The results showed a positive effect of dipping with solutions containing antioxidants as measured by peroxide value (PV), TBA-reactive substances (TBARS), and sensory profiling, e.g., rancid odor. Moreover, the oxidative stability increased with decreased storage temperature. The cod side-streams were in general most efficiently preserved by Duralox MANC, followed by the lipophilic rosemary extract (0.2%), compared to no dipping and dipping in NaCl solution and the lower concentration of the lipophilic rosemary extract (0.05%). The efficiency of the antioxidant treatments was independent of the side-stream fraction and storage temperature. Thus, using antioxidant dipping combined with low temperature storage is an efficient preservation method for maintaining the quality of the lipids in cod solid side-streams during their pre-valorization storage. Full article

The growing concern about ciguatera fish poisoning (CF) due to the expansion of the microorganisms producing ciguatoxins (CTXs) increased the need to develop a reliable and fast method for ciguatoxin detection to guarantee food safety. Cytotoxicity assay on the N2a cells sensitized with ouabain (O) and veratridine (V) is routinely used in ciguatoxin detection; however, this method has not been standardized yet. This study demonstrated the low availability of sodium channels in the N2a cells, the great O/V damage to the cells and the cell detachment when the cell viability is evaluated by the classical cytotoxicity assay and confirmed the absence of toxic effects caused by CTXs alone when using the methods that do not require medium removal such as lactate dehydrogenase (LDH) and Alamar blue assays. Different cell lines were evaluated as alternatives, such as human neuroblastoma, which was not suitable for the CTX detection due to the greater sensitivity to O/V and low availability of sodium channels. However, the HEK293 Nav cell line expressing the α1.6 subunit of sodium channels was sensitive to the ciguatoxin without the sensitization with O/V due to its expression of sodium channels. In the case of sensitizing the cells with O/V, it was possible to detect the presence of the ciguatoxin by the classical cytotoxicity MTT method at concentrations as low as 0.0001 nM CTX3C, providing an alternative cell line for the detection of compounds that act on the sodium channels. Full article

Crude polysaccharides extracted from the Codium sp. and Osmundea sp. macroalgae collected in different seasons (winter, spring and summer) from the Galician and North Portugal coasts were characterised, aiming to support their biomedical application to wound healing. An increase in polysaccharides’ sulphate content was registered from winter to summer, and higher values were obtained for Osmundea sp. In turn, the monosaccharide composition constantly changed with a decrease in glucose in Osmundea sp. from spring to winter. For Codium sp., a higher increase was noticed regarding glucose content in the Galician and Portugal coasts. Galactose was the major monosaccharide in all the samples, remaining stable in all seasons and collection sites. These results corroborate the sulphate content and antioxidant activity, since the Osmundea sp.-derived polysaccharides collected in summer exhibited higher scavenging radical ability. The biocompatibility and wound scratch assays revealed that the Osmundea sp. polysaccharide extracted from the Portugal coast in summer possessed more potential for promoting fibroblast migration. This study on seasonal variations of polysaccharides, sulphate content, monosaccharide composition and, consequently, biological properties provides practical guidance for determining the optimal season for algae harvest to standardise preparations of polysaccharides for the biomedical field. Full article

Tetrodotoxin (TTX) is an exceedingly toxic non-protein biotoxin that demonstrates remarkable selectivity and affinity for sodium channels on the excitation membrane of nerves. This property allows TTX to effectively obstruct nerve conduction, resulting in nerve paralysis and fatality. Although the mechanistic aspects of its toxicity are well understood, there is a dearth of literature addressing alterations in the neural microenvironment subsequent to TTX poisoning. In this research endeavor, we harnessed human pluripotent induced stem cells to generate cerebral organoids—an innovative model closely mirroring the structural and functional intricacies of the human brain. This model was employed to scrutinize the comprehensive transcriptomic shifts induced by TTX exposure, thereby delving into the neurotoxic properties of TTX and its potential underlying mechanisms. Our findings revealed 455 differentially expressed mRNAs (DEmRNAs), 212 differentially expressed lncRNAs (DElncRNAs), and 18 differentially expressed miRNAs (DEmiRNAs) in the TTX-exposed group when juxtaposed with the control cohort. Through meticulous Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein–protein interaction (PPI) analysis, we ascertained that these differential genes predominantly participate in the regulation of voltage-gated channels and synaptic homeostasis. A comprehensive ceRNA network analysis unveiled that DEmRNAs exert control over the expression of ion channels and neurocytokines, suggesting their potential role in mediating apoptosis. Full article

The rest raw materials of whitefish have great potential for increased utilisation and value creation. Whitefish heads have a high protein content and should be considered a healthy protein source for the growing population’s demands for sustainable protein. In this study, the heads of four different species of whitefish were processed via enzymatic hydrolysis, namely cod (Gadus morhua), cusk (Brosme bromse), haddock (Melanogrammus aeglefinus), and saithe (Pollachius virens), using three commercially available enzymes. Trials were conducted after 0, 3, and 6 months of the frozen storage of heads. A proximate analysis, molecular weight distribution, and protein solubility were evaluated for each of the products. The results show that, although the enzymatic hydrolysis of rest raw materials from different species of whitefish yielded products of slightly different characteristics, this process is viable for the production of high-quality protein from cod, cusk, haddock, and saithe heads. Six months of frozen storage of heads had a minimal effect on the yield and proximate composition of hydrolysates. Full article

Coenzyme Q (CoQ; ubiquinone) is an essential component of the respiratory chain. It is also a potent antioxidant that prevents oxidative damage to DNA, biological membranes, and lipoproteins. CoQ comprises a six-carbon ring with polar substituents that interact with electron acceptors and donors, and a hydrophobic polyisoprenoid chain that allows for its localization in cellular membranes. Human CoQ has 10 isoprenoid units (CoQ₁₀) within the polyisoprenoid chain. Few microorganisms produce CoQ₁₀. This work shows that Thraustochytrium sp. RT2316-16 produces CoQ₁₀ and CoQ₉. The CoQ₁₀ content in RT2316-16 depended strongly on the composition of the growth medium and the age of the culture, whereas the CoQ₉ content was less variable probably because it served a different function in the cell. Adding p-hydroxybenzoic acid to the culture media positively influenced the CoQ₁₀ content of the cell. The absence of some B vitamins and p-aminobenzoic acid in the culture medium negatively affected the growth of RT2316-16, but reduced the decline in CoQ₁₀ that otherwise occurred during growth. The highest content of CoQ₉ and CoQ₁₀ in the biomass were 855 μg g⁻¹ and 10 mg g⁻¹, respectively. The results presented here suggest that the thraustochytrid RT2316-16 can be a potential vehicle for producing CoQ₁₀. Metabolic signals that trigger the synthesis of CoQ₁₀ in RT2316-16 need to be determined for optimizing culture conditions. Full article

The hadal biosphere is the most mysterious ecosystem on the planet, located in a unique and extreme environment on Earth. To adapt to extreme environmental conditions, hadal microorganisms evolve special strategies and metabolisms to survive and reproduce. However, the secondary metabolites of the hadal microorganisms are poorly understood. In this study, we focused on the isolation and characterization of hadal fungi, screening the potential strains with bioactive natural products. The isolates obtained were detected further for the polyketide synthase (PKS) genes. Two isolates of Alternaria alternata were picked up as the representatives, which had the potential to synthesize active natural products. The epigenetic modifiers were used for the two A. alternata isolates to stimulate functional gene expression in hadal fungi under laboratory conditions. The results showed that the chemical epigenetic modifier, 5-Azacytidine (5-Aza), affected the phenotype, PKS gene expression, production of secondary metabolites, and antimicrobial activity of the hadal fungus A. alternata. The influence of epigenetic modification on natural products was strongest when the concentration of 5-Aza was 50 μM. Furthermore, the modification of epigenetic agents on hadal fungi under high hydrostatic pressure (HHP) of 40 MPa displayed significant effects on PKS gene expression, and also activated the production of new compounds. Our study demonstrates the high biosynthetic potential of cultivable hadal fungi, but also provides evidence for the utility of chemical epigenetic modifiers on active natural products from hadal fungi, providing new ideas for the development and exploitation of microbial resources in extreme environments. Full article

Two new cyclopiane diterpenes and a new cladosporin precursor, together with four known related compounds, were isolated from the marine sediment-derived fungus Penicillium antarcticum KMM 4670, which was re-identified based on phylogenetic inference from ITS, BenA, CaM, and RPB2 gene regions. The absolute stereostructures of the isolated cyclopianes were determined using modified Mosher’s method and quantum chemical calculations of the ECD spectra. The isolation from the natural source of two biosynthetic precursors of cladosporin from a natural source has been reported for the first time. The antimicrobial activities of the isolated compounds against Staphylococcus aureus, Escherichia coli, and Candida albicans as well as the inhibition of staphylococcal sortase A activity were investigated. Moreover, the cytotoxicity of the compounds to mammalian cardiomyocytes H9c2 was studied. As a result, new cyclopiane diterpene 13-epi-conidiogenone F was found to be a sortase A inhibitor and a promising anti-staphylococcal agent. Full article

Blue Haslea species are marine benthic pennate diatoms able to synthesize a blue-green water-soluble pigment, like marennine produced by H. ostrearia Simonsen. New species of Haslea synthetizing blue pigments were recently described (H. karadagensis, H. nusantara, H. provincialis and H. silbo). Their marennine-like pigments have allelopathic, antioxidative, antiviral and antibacterial properties, which have been demonstrated in laboratory conditions. Marennine is also responsible for the greening of oysters, for example, in the Marennes Oléron area (France), a phenomenon that has economical and patrimonial values. While blue Haslea spp. blooms have been episodically observed in natural environments (e.g., France, Croatia, USA), their dynamics have only been investigated in oyster ponds. This work is the first description of blue Haslea spp. benthic blooms that develop in open environments on the periphyton, covering turf and some macroalgae-like Padina. Different sites were monitored in the Mediterranean Sea (Corsica, France and Croatia) and two different blue Haslea species involved in these blooms were identified: H. ostrearia and H. provincialis. A non-blue Haslea species was also occasionally encountered. The benthic blooms of blue Haslea followed the phytoplankton spring bloom and occurred in shallow calm waters, possibly indicating a prominent role of light to initiate the blooms. In the absence of very strong winds and water currents that can possibly disaggregate the blue biofilm, the end of blooms coincided with the warming of the upper water masses, which might be profitable for other microorganisms and ultimately lead to a shift in the biofilm community. Full article

Bacteria are well-known to synthesize high molecular weight polysaccharides excreted in extracellular domain, which constitute their protective microenvironment. Several bacterial exopolysaccharides (EPS) are commercially available for skincare applications in cosmetic products due to their unique structural features, conferring valuable biological and/or textural properties. This review aims to give an overview of bacterial EPS, an important group of macromolecules used in cosmetics as actives and functional ingredients. For this purpose, the main chemical characteristics of EPS are firstly described, followed by the basics of the development of cosmetic ingredients. Then, a focus on EPS production, including upstream and downstream processes, is provided. The diversity of EPS used in the cosmetic industry, and more specifically of marine-derived EPS is highlighted. Marine bacteria isolated from extreme environments are known to produce EPS. However, their production processes are highly challenging due to high or low temperatures; yield must be improved to reach economically viable ingredients. The biological properties of marine-derived EPS are then reviewed, resulting in the highlight of the challenges in this field. Full article

Sepsis is a life-threatening complication of an infectious process that results from the excessive and uncontrolled activation of the host’s pro-inflammatory immune response to a pathogen. Lipopolysaccharide (LPS), also known as endotoxin, which is a major component of Gram-negative bacteria’s outer membrane, plays a key role in the development of Gram-negative sepsis and septic shock in humans. To date, no specific and effective drug against sepsis has been developed. This review summarizes data on LPS-binding proteins from marine invertebrates (ILBPs) that inhibit LPS toxic effects and are of interest as potential drugs for sepsis treatment. The structure, physicochemical properties, antimicrobial, and LPS-binding/neutralizing activity of these proteins and their synthetic analogs are considered in detail. Problems that arise during clinical trials of potential anti-endotoxic drugs are discussed. Full article

Marine polyphenols, including eckol(EK), dieckol(DK), and 8,8’-bieckol(BK), have attracted attention as bioactive ingredients for preventing Alzheimer’s disease (AD). Since AD is a multifactorial disorder, the present study aims to provide an unbiased elucidation of unexplored targets of AD mechanisms and a systematic prediction of effective preventive combinations of marine polyphenols. Based on the omics data between each compound and AD, a protein–protein interaction (PPI) network was constructed to predict potential hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to provide further biological insights. In the PPI network of the top 10 hub genes, AKT1, SRC, EGFR, and ESR1 were common targets of EK and BK, whereas PTGS2 was a common target of DK and BK. GO and KEGG pathway analysis revealed that the overlapped genes between each compound and AD were mainly enriched in EGFR tyrosine kinase inhibitor resistance, the MAPK pathway, and the Rap1 and Ras pathways. Finally, docking validation showed stable binding between marine polyphenols and their top hub gene via the lowest binding energy and multiple interactions. The results expanded potential mechanisms and novel targets for AD, and also provided a system-level insight into the molecular targets of marine polyphenols against AD. Full article

Antarctic krill (Euphausia superba) is the world’s largest resource of animal proteins and is thought to be a high-quality resource for future marine healthy foods and functional products. Therefore, Antarctic krill was degreased and separately hydrolyzed using flavourzyme, pepsin, papain, and alcalase. Protein hydrolysate (AKH) of Antarctic krill prepared by trypsin showed the highest Ca-chelating rate under the optimized chelating conditions: a pH of 8.0, reaction time of 50 min, temperature of 50 °C, and material/calcium ratio of 1:15. Subsequently, fourteen Ca-chelating peptides were isolated from APK by ultrafiltration and a series of chromatographic methods and identified as AK, EAR, AEA, VERG, VAS, GPK, SP, GPKG, APRGH, GVPG, LEPGP, LEKGA, FPPGR, and GEPG with molecular weights of 217.27, 374.40, 289.29, 459.50, 275.30, 300.36, 202.21, 357.41, 536.59, 328.37, 511.58, 516.60, 572.66, and 358.35 Da, respectively. Among fourteen Ca-chelating peptides, VERG presented the highest Ca-chelating ability. Ultraviolet spectrum (UV), Fourier Transform Infrared (FTIR), and scanning electron microscope (SEM) analysis indicated that the VERG-Ca chelate had a dense granular structure because the N-H, C=O and -COOH groups of VERG combined with Ca²⁺. Moreover, the VERG-Ca chelate is stable in gastrointestinal digestion and can significantly improve Ca transport in Caco-2 cell monolayer experiments, but phytate could significantly reduce the absorption of Ca derived from the VERG-Ca chelate. Therefore, Ca-chelating peptides from protein hydrolysate of Antarctic krill possess the potential to serve as a Ca supplement in developing healthy foods. Full article

Diseases such as obesity; cardiovascular diseases such as high blood pressure, myocardial infarction and stroke; digestive diseases such as celiac disease; certain types of cancer and osteoporosis are related to food. On the other hand, as the world’s population increases, the ability of the current food production system to produce food consistently is at risk. As a result, intensive agriculture has contributed to climate change and a major environmental impact. Research is, therefore, needed to find new sustainable food sources. One of the most promising sources of sustainable food raw materials is macroalgae. Algae are crucial to solving this nutritional deficiency because they are abundant in bioactive substances that have been shown to combat diseases such as hyperglycemia, diabetes, obesity, metabolic disorders, neurodegenerative diseases and cardiovascular diseases. Examples of these substances include polysaccharides such as alginate, fucoidan, agar and carrageenan; proteins such as phycobiliproteins; carotenoids such as β-carotene and fucoxanthin; phenolic compounds; vitamins and minerals. Seaweed is already considered a nutraceutical food since it has higher protein values than legumes and soy and is, therefore, becoming increasingly common. On the other hand, compounds such as polysaccharides extracted from seaweed are already used in the food industry as thickening agents and stabilizers to improve the quality of the final product and to extend its shelf life; they have also demonstrated antidiabetic effects. Among the other bioactive compounds present in macroalgae, phenolic compounds, pigments, carotenoids and fatty acids stand out due to their different bioactive properties, such as antidiabetics, antimicrobials and antioxidants, which are important in the treatment or control of diseases such as diabetes, cholesterol, hyperglycemia and cardiovascular diseases. That said, there have already been some studies in which macroalgae (red, green and brown) have been incorporated into certain foods, but studies on gluten-free products are still scarce, as only the potential use of macroalgae for this type of product is considered. Considering the aforementioned issues, this review aims to analyze how macroalgae can be incorporated into foods or used as a food supplement, as well as to describe the bioactive compounds they contain, which have beneficial properties for human health. In this way, the potential of macroalgae-based products in eminent diseases, such as celiac disease, or in more common diseases, such as diabetes and cholesterol complications, can be seen. Full article

Obesity is a multifactorial disease characterized by an excessive accumulation of fat, which in turn poses a significant risk to health. Bioactive compounds obtained from macroalgae have demonstrated their efficacy in combating obesity in various animal models. The green macroalgae Caulerpa lentillifera (CL) contains numerous active constituents. Hence, in the present study, we aimed to elucidate the beneficial anti-obesity effects of extracts derived from C. lentillifera using a Caenorhabditis elegans obesity model. The ethanol (CLET) and ethyl acetate (CLEA) extracts caused a significant decrease in fat consumption, reaching up to approximately 50–60%. Triglyceride levels in 50 mM glucose-fed worms were significantly reduced by approximately 200%. The GFP-labeled dhs-3, a marker for lipid droplets, exhibited a significant reduction in its level to approximately 30%. Furthermore, the level of intracellular ROS displayed a significant decrease of 18.26 to 23.91% in high-glucose-fed worms treated with CL extracts, while their lifespan remained unchanged. Additionally, the mRNA expression of genes associated with lipogenesis, such as sbp-1, showed a significant down-regulation following treatment with CL extracts. This finding was supported by a significant decrease (at 16.22–18.29%) in GFP-labeled sbp-1 gene expression. These results suggest that C. lentillifera extracts may facilitate a reduction in total fat accumulation induced by glucose through sbp-1 pathways. In summary, this study highlights the anti-obesity potential of compounds derived from C. lentillifera extracts in a C. elegans model of obesity, mediated by the suppression of lipogenesis pathways. Full article

Microalgae have gained attention as a promising source of chlorophylls and carotenoids in various industries. However, scaling up of conventional bubble columns presents challenges related to cell sedimentation and the presence of non-photosynthetic cells due to non-circulating zones and decreased light accessibility, respectively. Therefore, this study aimed to evaluate the newly developed continuously circulated bioreactor ROSEMAX at both laboratory and pilot scales, compared to a conventional bubble column. There was no significant difference in the biomass production and photosynthetic pigment content of Tetraselmis sp. cultivated at the laboratory scale (p > 0.05). However, at the pilot scale, the biomass cultured in ROSEMAX showed significantly high biomass (1.69 ± 0.11 g/L, dry weight, DW), chlorophyll-a (14.60 ± 0.76 mg/g, DW), and total carotene (5.64 ± 0.81 mg/g, DW) concentrations compared to the conventional bubble column (1.17 ± 0.11 g/L, DW, 10.67 ± 0.72 mg/g, DW, 3.21 ± 0.56 mg/g, DW, respectively) (p ≤ 0.05). Flow cytometric analyses confirmed that the proportion of Tetraselmis sp. live cells in the culture medium of ROSEMAX was 32.90% higher than that in the conventional bubble column, with a photosynthetic efficiency 1.14 times higher. These results support suggestions to use ROSEMAX as a bioreactor for industrial-scale applications. Full article

Six new thiodiketopiperazine-class alkaloids lecanicilliums A–F were isolated from the mangrove sediment-derived fungus Lecanicillium kalimantanense SCSIO41702, together with thirteen known analogues. Their structures were determined by spectroscopic analysis. The absolute configurations were determined by quantum chemical calculations. Electronic circular dichroism (ECD) spectra and the structure of Lecanicillium C were further confirmed by a single-crystal X-ray diffraction analysis. Lecanicillium A contained an unprecedented 6/5/6/5/7/6 cyclic system with a spirocyclic center at C-2′. Biologically, lecanicillium E, emethacin B, and versicolor A displayed significant cytotoxicity against human lung adenocarcinoma cell line H1975, with IC₅₀ values of 7.2~16.9 μM, and lecanicillium E also showed antibacterial activity against four pathogens with MIC values of 10~40 μg/mL. Their structure–activity relationship is also discussed. Full article

Soft corals, recognized as sessile marine invertebrates, rely mainly on chemical, rather than physical defense, by secreting intricate secondary metabolites with plausible pharmaceutical implication. Their ecological niche encompasses a diverse community of symbiotic microorganisms which potentially contribute to the biosynthesis of these bioactive metabolites. The emergence of new viruses and heightened viral resistance underscores the urgency to explore novel pharmacological reservoirs. Thus, marine organisms, notably soft corals and their symbionts, have drawn substantial attention. In this study, the chemical composition of four Mauritian soft corals: Sinularia polydactya, Cespitularia simplex, Lobophytum patulum, and Lobophytum crassum was investigated using LC–MS techniques. Concurrently, Illumina 16S metagenomic sequencing was used to identify the associated bacterial communities in the named soft corals. The presence of unique biologically important compounds and vast microbial communities found therein was further followed up to assess their antiviral effects against SARS-CoV-2 and HPV pseudovirus infection. Strikingly, among the studied soft corals, L. patulum displayed an expansive repertoire of unique metabolites alongside a heightened bacterial consort. Moreover, L. patulum extracts exerted some promising antiviral activity against SARS-CoV-2 and HPV pseudovirus infection, and our findings suggest that L. patulum may have the potential to serve as a therapeutic agent in the prevention of infectious diseases, thereby warranting further investigation. Full article

Several sialoglycopeptides were isolated from several fish eggs and exerted anti-osteoporosis effects. However, few papers have explored sialoglycopeptide from tuna eggs (T-ES). Here, a novel T-ES was prepared through extraction with KCl solution and subsequent enzymolysis. Pure T-ES was obtained through DEAE-Sepharose ion exchange chromatography and sephacryl S-300 gel filtration chromatography. The T-ES was composed of 14.07% protein, 73.54% hexose, and 8.28% Neu5Ac, with a molecular weight of 9481 Da. The backbone carbohydrate in the T-ES was →4)-β-D-GlcN-(1→3)-α-D-GalN-(1→3)-β-D-Glc-(1→2)-α-D-Gal-(1→2)-α-D-Gal-(1→3)-α-D-Man-(1→, with two branches of β-D-GlcN-(1→ and α-D-GalN-(1→ linking at o-4 in →2,4)-α-D-Gal-(1→. Neu5Ac in the T-ES was linked to the branch of α-D-GlcN-(1→. A peptide chain, Ala-Asp-Asn-Lys-Ser*-Met-Ile that was connected to the carbohydrate chain through O-glycosylation at the –OH of serine. Furthermore, in vitro data revealed that T-ES could remarkably enhance bone density, bone biomechanical properties, and bone microstructure in SAMP mice. The T-ES elevated serum osteogenesis-related markers and reduced bone resorption-related markers in serum and urine. The present study’s results demonstrated that T-ES, a novel sialoglycopeptide, showed significant anti-osteoporosis effects, which will accelerate the utilization of T-ES as an alternative marine drug or functional food for anti-osteoporosis. Full article

Phycobiliproteins (PBPs) are natural water-soluble pigment proteins, which constitute light-collecting antennae, and function in algae photosynthesis, existing in cyanobacteria, red algae, and cryptomonads. They are special pigment–protein complexes in algae with a unique structure and function. According to their spectral properties, PBPs can be mainly divided into three types: allophycocyanin, phycocyanin, and PE. At present, there are two main sources of PBPs: one is natural PBPs extracted from algae and the other way is recombinant PBPs which are produced in engineered microorganisms. The covalent connection between PBP and streptavidin was realized by gene fusion. The bridge cascade reaction not only improved the sensitivity of PBP as a fluorescent probe but also saved the preparation time of the probe, which expands the application range of PBPs as fluorescent probes. In addition to its function as a light-collecting antenna in photosynthesis, PBPs also have the functions of biological detection, ion detection, and fluorescence imaging. Notably, increasing studies have designed novel PBP-based far-red fluorescent proteins, which enable the tracking of gene expression and cell fate. Full article

Diatoms are responsible for the fixation of ca. 20% of the global CO2 and live associated with bacteria that utilize the organic substances produced by them. Current research trends in marine microbial ecology show which diatom and bacteria interact mediated through the production and exchange of infochemicals. Polyunsaturated aldehydes (PUA) are organic molecules released by diatoms that are considered to have infochemical properties. In this work, we investigated the possible role of PUA as a mediator in diatom–bacteria interactions. To this end, we compare the PUA profile of a newly isolated oceanic PUA producer diatom, Cyclotella cryptica, co-cultured with and without associated bacteria at two phosphate availability conditions. We found that the PUA profile of C. cryptica cultured axenically was different than its profile when it was co-cultured with autochthonous (naturally associated) and non-autochthonous bacteria (unnaturally inoculated). We also observed that bacterial presence significantly enhanced diatom growth and that C. cryptica modulated the percentage of released PUA in response to the presence of bacteria, also depending on the consortium type. Based on our results, we propose that this diatom could use released PUA as a specific organic matter sign to attract beneficial bacteria for constructing its own phycosphere, for more beneficial growth. Full article

C1q domain-containing proteins (C1qDC proteins) unexpectedly turned out to be widespread molecules among a variety of invertebrates, despite their lack of an integral complement system. Despite the wide distribution in the genomes of various invertebrates, data on the structure and properties of the isolated and characterized C1qDC proteins, which belong to the C1q/TNF superfamily, are sporadic, although they hold great practical potential for the creation of new biotechnologies. This review not only summarizes the current data on the properties of already-isolated or bioengineered C1qDC proteins but also projects further strategies for their study and biomedical application. It has been shown that further broad study of the carbohydrate specificity of the proteins can provide great opportunities, since for many of them only interactions with pathogen-associated molecular patterns (PAMPs) was evaluated and their antimicrobial, antiviral, and fungicidal activities were studied. However, data on the properties of C1qDC proteins, which researchers originally discovered as lectins and therefore studied their fine carbohydrate specificity and antitumor activity, intriguingly show the great potential of this family of proteins for the creation of targeted drug delivery systems, vaccines, and clinical assays for the differential diagnosis of cancer. The ability of invertebrate C1qDC proteins to recognize patterns of aberrant glycosylation of human cell surfaces and interact with mammalian immunoglobulins indicates the great biomedical potential of these molecules. Full article

The shift from the terrestrial to the marine environment to discover natural products has given rise to novel bioactive compounds, some of which have been approved for human medicine. However, the ocean, which makes up nearly three-quarters of the Earth’s surface, contains macro- and microorganisms whose natural products are yet to be explored. Among these underexplored marine organisms are macroalgae and their symbiotic microbes, such as Bacillota, a phylum of mostly Gram-positive bacteria previously known as Firmicutes. Macroalgae-associated Bacillota often produce chemical compounds that protect them and their hosts from competitive and harmful rivals. Here, we summarised the natural products made by macroalgae-associated Bacillota and their pharmacological properties. We discovered that these Bacillota are efficient producers of novel biologically active molecules. However, only a few macroalgae had been investigated for chemical constituents of their Bacillota: nine brown, five red and one green algae. Thus, Bacillota, especially from the marine habitat, should be investigated for potential pharmaceutical leads. Moreover, additional diverse biological assays for the isolated molecules of macroalgae Bacillota should be implemented to expand their bioactivity profiles, as only antibacterial properties were tested for most compounds. Full article