The biocontrol fungus Trichoderma harzianum, from both marine and terrestrial environments, has attracted considerable attention. T. harzianum has a tremendous potential to produce a variety of bioactive secondary metabolites (SMs), which are an important source of new herbicides and antibiotics. This review prioritizes the SMs of T. harzianum from 1988 to June 2022, and their relevant biological activities. Marine-derived SMs, especially terpenoids, polyketides, and macrolides compounds, occupy a significant proportion of natural products from T. harzianum, deserving more of our attention.

To explore the application of chitosan-gentamicin conjugate (CS-GT) in inhibiting Vibrio parahaemolyticus (V. parahaemolyticus), which is an important pathogen in aquatic animals worldwide, the antimicrobial activity of CS-GT and the effects of a CS-GT dose on the intestine histopathology and intestinal flora of V. parahaemolyticus-infected shrimps were explored. The results showed that CS-GT possessed broad-spectrum antibacterial activity, with minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and half inhibitory concentration (IC50) of 20.00 ± 0.01, 75.00 ± 0.02 and 18.72 ± 3.17 μg/mL for V. parahaemolyticus, respectively. Further scanning electron microscope and cell membrane damage analyses displayed that the electrostatic interaction of CS-GT with cell membrane strengthened after CS grafted GT, resulting in leakage of nucleic acid and electrolytes of V. parahaemolyticus. On the other hand, histopathology investigation indicated that high (100 mg/kg) and medium (50 mg/kg) doses of CS-GT could alleviate the injury of a shrimp's intestine caused by V. parahaemolyticus. Further 16S rRNA gene sequencing analysis found high and medium dose of CS-GT could effectively inhabit V. parahaemolyticus invasion and reduce intestinal dysfunction. In conclusion, CS-GT possesses good antibacterial activity and could protect shrimps from pathogenic bacteria infection.

The structural characterization of lipopolysaccharides has critical implications for some biomedical applications, and marine bacteria are an inimitable source of new glyco-structures potentially usable in medicinal chemistry. On the other hand, lipopolysaccharides of marine Gram-negative bacteria present certain structural features that can help the understanding of the adaptation processes. The deep-sea marine Gram-negative bacterium Idiomarina zobellii KMM 231T, isolated from a seawater sample taken at a depth of 4000 m, represents an engaging microorganism to investigate in terms of its cell wall components. Here, we report the structural study of the R-type lipopolysaccharide isolated from I. zobellii KMM 231T that was achieved through a multidisciplinary approach comprising chemical analyses, NMR spectroscopy, and MALDI mass spectrometry. The lipooligosaccharide turned out to be characterized by a novel and unique pentasaccharide skeleton containing a very short mono-phosphorylated core region and comprising terminal neuraminic acid. The lipid A was revealed to be composed of a classical disaccharide backbone decorated by two phosphate groups and acylated by i13:0(3-OH) in amide linkage, i11:0 (3-OH) as primary ester-linked fatty acids, and i11:0 as a secondary acyl chain.

NMR data prediction is increasingly important in structure elucidation. The impact of force field selection was assessed, along with geometry and energy cutoffs. Based on the conclusions, we propose a new approach named mix-J-DP4, which provides a remarkable increase in the confidence level of complex stereochemical assignments-100% in our molecular test set-with a very modest increment in computational cost.

Marine microalgae, diatoms, are considered a source of a wide range of high-value compounds, and numerous studies indicate their biotechnological potential in the food and feed industry, cosmetic industry, nanotechnology, pharmaceutical industry, biodiesel production, fertilizers, and wastewater treatment. The aim of this study was to compare the growth, chemical profiles, and antioxidant activity of the diatom Skeletonema grevillei cultivated in a bioreactor and an incubation-shaking cabinet at different growth phases (after 192 and 312 h). Growth was monitored by evaluating cell density with the Sedgewick Rafter chamber, and the collected biomass was extracted with 70% ethanol assisted by ultrasound. Extracts were evaporated to dryness and compounds were identified in derivatized form by gas chromatography and mass spectrometry (GC-MS) analysis, while antioxidant capacity was evaluated by DPPH and ORAC. Significantly faster growth was observed in the bioreactor than in the incubation-shaking cabinet. Oleamide, palmitelaidic acid, glycerol monostearate, myristic acid, cholesterol, eicosapentaenoic acid, 1-monopalmitin, and 24-methylene cholesterol were identified as the major compounds in both systems. Among them, oleamide was the dominant compound in both systems. It is also shown that prolonging the cultivation period had a direct effect on increasing the extract yield. The highest DPPH inhibition (11.4 ± 1%) and ORAC values (93.3 ± 8.4 mM TE) were obtained for the S. grevillei extract recovered from the bioreactor after 312 h. The obtained results contribute to the possibility of using S. grevillei for various biotechnological applications in the future.

Analytical scale chemical/cultivation profiling prioritized the Australian marine-derived fungus Aspergillus noonimiae CMB-M0339. Subsequent investigation permitted isolation of noonindoles A-F (5-10) and detection of eight minor analogues (i-viii) as new examples of a rare class of indole diterpene (IDT) amino acid conjugate, indicative of an acyl amino acid transferase capable of incorporating a diverse range of amino acid residues. Structures for 5-10 were assigned by detailed spectroscopic and X-ray crystallographic analysis. The metabolites 5-14 exhibited no antibacterial properties against G-ve and G+ve bacteria or the fungus Candida albicans, with the exception of 5 which exhibited moderate antifungal activity.

Phycocyanin is an excellent antioxidant with anti-inflammatory effects on which recent studies are growing; however, its specific target remains unclear. Linear tetrapyrrole compounds such as bilirubin have been shown to lead to the induction of heme oxygenase 1 expression in vivo, thus achieving antioxidant and anti-inflammatory effects. Phycocyanin is bound internally with linear tetrapyrrole phycocyanobilin in a similar structure to bilirubin. We speculate that there is probably a way of inducing the expression of heme oxygenase 1, with which tissue oxidative stress and inflammation can be inhibited, thus inhibiting pulmonary fibrosis caused by oxidative damage and inflammation of lung. By optimizing the enzymatic hydrolysis process, phycocyanobilin-bound phycocyanin peptide were obtained, and its in vitro antioxidant, anti-inflammatory, and anti-pulmonary fibrosis activities were investigated. The results show that the phycocyanobilin peptide was able to alleviate oxidative and inflammatory damage in cells through the Keap1-Nrf2-HO-1 pathway, which in turn relieved pulmonary fibrosis symptoms.

Novel personal care products are necessary to cope with the growing market demand for sustainable green products. In this context, this work deals with the formulation and fundamental physicochemical and rheological characterization of different natural personal care products using bioactive fractions from Chondrus crispus red macroalgae extracted under optimized green conditions. Body milks, body oils and shampoos were supplemented with soluble extracts with antioxidant features recovered after hydrothermal (200 °C) and microwave (170 °C)- and ultrasound (80 °C)-assisted extraction of the red macroalgae used as raw material. Formulated products were also compared with those prepared using (±)-α-tocopherol and butylhydroxytoluene standards. Body scrubs were formulated with the remaining solids (<2.25 %) after microwave hydrodiffusion and gravidity treatment of the macroalgae. Results indicated that selected extracts provided personal care products with similar or even better physicochemical, color and viscous features than those supplemented with (±)-α-tocopherol or butylhydroxytoluene commercial antioxidants. Rheological profiles indicated that it is possible to develop personal care products with adequate viscous behavior (102-105 mPa s, at 1 s-1), comparable with their synthetic counterparts. To conclude, the addition of antioxidant extracts led to lower apparent viscosity values suggesting an advantage from the skin applicability point of view, jointly with the absence of both the hysteresis phenomenon and water syneresis of the proposed formulations.

A potential fucoidan-based PEGylated PLGA nanoparticles (NPs) offering a proper delivery of N-methyl anthranilic acid (MA, a model of hydrophobic anti-inflammatory drug) have been developed via the formation of fucoidan aqueous coating surrounding PEGylated PLGA NPs. The optimum formulation (FuP2) composed of fucoidan:m-PEG-PLGA (1:0.5 w/w) with particle size (365 ± 20.76 nm), zeta potential (-22.30 ± 2.56 mV), % entrapment efficiency (85.45 ± 7.41), drug loading (51.36 ± 4.75 µg/mg of NPs), % initial burst (47.91 ± 5.89), and % cumulative release (102.79 ± 6.89) has been further investigated for the anti-inflammatory in vivo study. This effect of FuP2 was assessed in rats' carrageenan-induced acute inflammation model. The average weight of the paw edema was significantly lowered (p ≤ 0.05) by treatment with FuP2. Moreover, cyclooxygenase-2 and tumor necrosis factor-alpha immunostaining were decreased in FuP2 treated group compared to the other groups. The levels of prostaglandin E2, nitric oxide, and malondialdehyde were significantly reduced (p ≤ 0.05) in the FuP2-treated group. A significant reduction (p ≤ 0.05) in the expression of interleukins (IL-1β and IL-6) with an improvement of the histological findings of the paw tissues was observed in the FuP2-treated group. Thus, fucoidan-based PEGylated PLGA-MA NPs are a promising anti-inflammatory delivery system that can be applied for other similar drugs potentiating their pharmacological and pharmacokinetic properties.

Fucales are an order within the Phaeophyceae that include most of the common littoral seaweeds in temperate and subtropical coastal regions. Many species of this order have long been a part of human culture with applications as food, feedand remedies in folk medicine. Apart from their high nutritional value, these seaweeds are also a well-known reservoir of multiple bioactive compounds with great industrial interest. Among them, phlorotannins, a unique and diverse class of brown algae-exclusive phenolics, have gathered much attention during the last few years due to their numerous potential health benefits. However, due to their complex structural features, combined with the scarcity of standards, it poses a great challenge to the identification and characterization of these compounds, at least with the technology currently available. Nevertheless, much effort has been taken towards the elucidation of the structural features of phlorotannins, which have resulted in relevant insights into the chemistry of these compounds. In this context, this review addresses the major contributions and technological advances in the field of phlorotannins extraction and characterization, with a particular focus on Fucales.

Functional ingredients for human health have recently become the focus of research. One such potentially versatile therapeutic component is fucose-containing sulfated polysaccharides (FCSPs), referred to as fucoidans. The exploitation of marine brown algae provides a rich source of FCSPs because of their role as a structural component of the cell wall. Fucoidans are characterized by a sulfated fucose backbone. However, the structural characterization of FCSPs is impeded by their structural diversity, molecular weight, and complexity. The extraction and purification conditions significantly influence the yield and structural alterations. Inflammation is the preliminary response to potentially injurious inducements, and it is of the utmost importance for modulation in the proper direction. Improper manipulation and/or continuous stimuli could have detrimental effects in the long run. The web of immune responses mediated through multiple modulatory/cell signaling components can be addressed through functional ingredients, benefiting patients with no side effects. In this review, we attempted to address the involvement of FCSPs in the stimulation/downregulation of immune response cell signaling. The structural complexity and its foremost influential factor, extraction techniques, have also attracted attention, with concise details on the structural implications of bioactivity.

Cadmium (Cd) is a widespread environmental toxicant that can cause severe hepatic injury. Oyster protein hydrolysates (OPs) have potential effects on preventing liver disease. In this study, thirty mice were randomly divided into five groups: the control, Cd, Cd + ethylenediaminetetraacetic acid (EDTA, 100 mg/kg), and low/high dose of OPs-treatment groups (100 mg/kg or 300 mg/kg). After continuous administration for 7 days, the ameliorative effect of OPs on Cd-induced acute hepatic injury in Cd-exposed mice was assessed. The results showed that OPs significantly improved the liver function profiles (serum ALT, AST, LDH, and ALP) in Cd-exposed mice. Histopathological analysis showed that OPs decreased apoptotic bodies, hemorrhage, lymphocyte accumulation, and inflammatory cell infiltration around central veins. OPs significantly retained the activities of SOD, CAT, and GSH-Px, and decreased the elevated hepatic MDA content in Cd-exposed mice. In addition, OPs exhibited a reductive effect on the inflammatory responses (IL-1β, IL-6, and TNF-α) and inhibitory effects on the expression of inflammation-related proteins (MIP-2 and COX-2) and the ERK/NF-κB signaling pathway. OPs suppressed the development of hepatocyte apoptosis (Bax, caspase-3, and Blc-2) and the activation of the PI3K/AKT signaling pathway in Cd-exposed mice. In conclusion, OPs ameliorated the Cd-induced hepatic injury by inhibiting oxidative damage and inflammatory responses, as well as the development of hepatocyte apoptosis via regulating the ERK/NF-κB and PI3K/AKT-related signaling pathways.

Endothelial-mesenchymal transition (EndMT) is a process by which endothelial cells (ECs) transition into mesenchymal cells (e.g., myofibroblasts and smooth muscle cells) and induce fibrosis of cells/tissues, due to ischemic conditions in the heart. Previously, we reported that echinochrome A (EchA) derived from sea urchin shells can modulate cardiovascular disease by promoting anti-inflammatory and antioxidant activity; however, the mechanism underlying these effects was unclear. We investigated the role of EchA in the EndMT process by treating human umbilical vein ECs (HUVECs) with TGF-β2 and IL-1β, and confirmed the regulation of cell migration, inflammatory, oxidative responses and mitochondrial dysfunction. Moreover, we developed an EndMT-induced myocardial infarction (MI) model to investigate the effect of EchA in vivo. After EchA was administered once a day for a total of 3 days, the histological and functional improvement of the myocardium was investigated to confirm the control of the EndMT. We concluded that EchA negatively regulates early or inflammation-related EndMT and reduces the myofibroblast proportion and fibrosis area, meaning that it may be a potential therapy for cardiac regeneration or cardioprotection from scar formation and cardiac fibrosis due to tissue granulation. Our findings encourage the study of marine bioactive compounds for the discovery of new therapeutics for recovering ischemic cardiac injuries.

Biological invasion is the successful spread and establishment of a species in a novel environment that adversely affects the biodiversity, ecology, and economy. Both invasive and non-invasive species of the Caulerpa genus secrete more than thirty different secondary metabolites. Caulerpin is one of the most common secondary metabolites in genus Caulerpa. In this study, caulerpin found in invasive Caulerpa cylindracea and non-invasive Caulerpa lentillifera extracts were analyzed, quantified, and compared using high-performance thin layer chromatography (HPTLC) for the first time. The anticancer activities of caulerpin against HCT-116 and HT-29 colorectal cancer (CRC) cell lines were also tested. Caulerpin levels were found higher in the invasive form (108.83 ± 5.07 µg mL-1 and 96.49 ± 4.54 µg mL-1). Furthermore, caulerpin isolated from invasive Caulerpa decreased cell viability in a concentration-dependent manner (IC50 values were found between 119 and 179 µM), inhibited invasion-migration, and induced apoptosis in CRC cells. In comparison, no cytotoxic effects on the normal cell lines (HDF and NIH-3T3) were observed. In conclusion, HPTLC is a quick and novel method to investigate the caulerpin levels found in Caulerpa extracts, and this paper proposes an alternative utilization method for invasive C. cylindracea due to significant caulerpin content compared to non-invasive C. lentillifera.

Chronic inflammation can extensively burden a healthcare system. Several synthetic anti-inflammatory drugs are currently available in clinical practice, but each has its own side effect profile. The planet is gifted with vast and diverse oceans, which provide a treasure of bioactive compounds, the chemical structures of which may provide valuable pharmaceutical agents. Marine organisms contain a variety of bioactive compounds, some of which have anti-inflammatory activity and have received considerable attention from the scientific community for the development of anti-inflammatory drugs. This review describes such bioactive compounds, as well as crude extracts (published during 2010-2022) from echinoderms: namely, sea cucumbers, sea urchins, and starfish. Moreover, we also include their chemical structures, evaluation models, and anti-inflammatory activities, including the molecular mechanism(s) of these compounds. This paper also highlights the potential applications of those marine-derived compounds in the pharmaceutical industry to develop leads for the clinical pipeline. In conclusion, this review can serve as a well-documented reference for the research progress on the development of potential anti-inflammatory drugs from echinoderms against various chronic inflammatory conditions.

Selenium (Se) and fish oil (FO) exert anti-epidermal growth factor receptor (EGFR) action on tumors. This study aimed to compare the anti-cancer efficacy of EGFR inhibitors (gefitinib and erlotinib) alone and in combination with nutritional supplements of Se/FO in treating lung cancer. Lewis LLC1 tumor-bearing mice were treated with a vehicle or Se/FO, gefitinib or gefitinib plus Se/FO, and erlotinib or erlotinib plus Se/FO. The tumors were assessed for mRNA and protein expressions of relevant signaling molecules. Untreated tumor-bearing mice had the lowest body weight and highest tumor weight and volume of all the mice. Mice receiving the combination treatment with Se/FO and gefitinib or erlotinib had a lower tumor volume and weight and fewer metastases than did those treated with gefitinib or erlotinib alone. The combination treatment exhibited greater alterations in receptor signaling molecules (lower EGFR/TGF-β/TβR/AXL/Wnt3a/Wnt5a/FZD7/β-catenin; higher GSK-3β) and immune checkpoint molecules (lower PD-1/PD-L1/CD80/CTLA-4/IL-6; higher NKp46/CD16/CD28/IL-2). These mouse tumors also had lower angiogenesis, cancer stemness, epithelial to mesenchymal transitions, metastases, and proliferation of Ki-67, as well as higher cell cycle arrest and apoptosis. These preliminary results showed the Se/FO treatment enhanced the therapeutic efficacies of gefitinib and erlotinib via modulating multiple signaling pathways in an LLC1-bearing mouse model.

α-conotoxin AuIB is the only one of the 4/6 type α-conotoxins (α-CTxs) that inhibits the γ-aminobutyric acid receptor B (GABABR)-coupled N-type calcium channel (CaV2.2). To improve its inhibitory activity, a series of variants were synthesized and evaluated according to the structure-activity relationships of 4/7 type α-CTxs targeting GABABR-coupled CaV2.2. Surprisingly, only the substitution of Pro7 with Arg results in a 2-3-fold increase in the inhibition of GABABR-coupled CaV2.2 (IC50 is 0.74 nM); substitutions of position 9-12 with basic or hydrophobic amino acid and the addition of hydrophobic amino acid Leu or Ile at the second loop to mimic 4/7 type α-CTxs all failed to improve the inhibitory activity of AuIB against GABABR-coupled CaV2.2. Interestingly, the most potent form of AuIB[P7R] has disulfide bridges of "1-4, 2-3" (ribbon), which differs from the "1-3, 2-4" (globular) in the isoforms of wildtype AuIB. In addition, AuIB[P7R](globular) displays potent analgesic activity in the acetic acid writhing model and the partial sciatic nerve injury (PNL) model. Our study demonstrated that 4/6 type α-CTxs, with the disulfide bridge connectivity "1-4, 2-3," are also potent inhibitors for GABABR-coupled CaV2.2, exhibiting potent analgesic activity.

Phenylahistin is a naturally occurring marine product with a diketopiperazine structure that can bind to the colchicine site of microtubulin as a possible anticancer agent. To develop more potent microtubule inhibitors, novel phenylahistin derivatives were designed and synthesized based on the co-crystal complexes of phenylahistin derivatives and microtubulin. We established a focused library of imidazole-type molecules for the introduction of different groups to the C-ring and A-ring of phenylahistin. Structure-activity relationship studies indicated that appropriate hydrocarbon substituents and unsaturated alkenyl substituents at the 1-position of the imidazole group are important for improving the activity of such compounds. In addition, this study found that propylamine groups could maintain the activity of these compounds, as exemplified by compound 16d (IC50 = 5.38 nM, NCI-H460). Compound 15p (IC50 = 1.03 nM, NCI-H460) with an allyl group exhibited potent cytotoxic activity at the nanomolar level against human lung cancer cell lines. Immunofluorescence assay indicated that compound 15p could efficiently inhibited microtubule polymerization and induced a high expression of caspase-3. 15p also displayed good pharmacokinetic characteristics in vitro. Additionally, the growth of H22 transplanted tumors was significantly inhibited in BALB/c mice when 15p alone was administered at 4 mg/kg, and the tumor inhibition rate was as much as 65%. Importantly, the continuous administration of 15p resulted in a lower toxicity than that of docetaxel (10 mg/kg) and cyclophosphamide (20 mg/kg). Overall, the novel allyl-imidazole-diketopiperazine-type derivatives could be considered safe and effective potential agents for cancer treatment.

Most reports on signal peptides focus on their ability to affect the normal folding of proteins, thereby affecting their secreted expression, while few studies on its effects on enzymatic properties were published. Therefore, biochemical characterization and comparison of alginate lyase rALYI1/rALYI1-1 (rALYI1: without signal peptides; rALYI1-1:with signal peptides) were conducted in our study, and the results showed that the signal peptide affected the biochemical properties, especially in temperature and pH. rALYI1 (32.15 kDa) belonging to polysaccharide lyase family 7 was cloned from sea-cucumber-gut bacterium Tamlana sp. I1. The optimum temperature of both rALYI1 and rALYI1-1 was 40 °C, but the former had a wider optimum temperature range and better thermal stability. The optimum pH of rALYI1 and rALYI1-1 were 7.6 and 8.6, respectively. The former was more stable and acid resistant. Noticeably, rALYI1 was a salt-activated enzyme and displayed remarkable salt tolerance. Alginate, an essential polysaccharide in algae and Pseudomonas aeruginosa biofilms, is composed of α-L-guluronate and β-D-mannuronate. It is also found in our study that rALYI1 is also effective in removing mature biofilms compared with controls. In conclusion, the signal peptide affects several biochemical properties of the enzyme, and alginate lyase rALYI1 may be an effective method for inhibiting biofilm formation of Pseudomonas aeruginosa.

The dinoflagellate Ostreopsis cf. ovata produces several families of toxic polyketides. Despite only a few field measurements of these phycotoxins in seawater and aerosols, they are believed to be responsible for dermatitis and the toxic inhalations reported during blooms of this species. Therefore, the stability of these compounds in seawater is essential to understanding the causes of these symptoms, however, this has never been assessed. In the current study, the optimization of a solid phase extraction (SPE) procedure was first performed to ensure the most efficient extraction of all phycotoxins known to be produced by this strain, including the recently described liguriatoxins. The SPE cartridge SDBL® under non acidified conditions offered the best option. The stability of the ovatoxins and the liguriatoxins under biotic and abiotic stress was assessed by exposing the spent medium of a culture of Ostreopsis cf. ovata to its bacterial consortium and natural sunlight. A rapid biotic transformation was detected for both families of compounds. When exposed to bacteria, the half-lives of the ovatoxins were reached before 10 h and at 36 h, 97% of these toxins had been transformed. The half-lives of the liguriatoxins were 10 h under these conditions. Photolysis (abiotic degradation) of the ovatoxins (T1/2 < 36 h) was faster than for the liguriatoxins (T1/2 > 62 h). Although none of the catabolites of these phycotoxins were thoroughly identified, an untargeted metabolomics approach combined with molecular networking highlighted the presence of several compounds exhibiting structural similarities with the ovatoxins. Additional work should confirm the preliminary findings on these potential ovatoxins' catabolites and their biological properties. The rapid transformation of O. cf. ovata's phycotoxins introduces questions concerning their presence in seawater and their dispersion in the sea spray aerosols. The compounds involved in the toxic inhalations and dermatitis often experienced by beachgoers may stem from the catabolites of these toxins or even unrelated and as yet unidentified compounds.

This study aimed to purify and identify antiphotoaging peptides from oyster (Crassostrea hongkongensis) protein enzymatic hydrolysates (OPEH) and to investigate the possible mechanism underlying its antiphotoaging effect. Multiple methods (Ultrafiltration, G25 Chromatography, RP-HPLC, and LC/MS/MS) had been used for this purpose, and eventually, two peptides, including WNLNP and RKNEVLGK, were identified. Particularly, WNLNP exerted remarkable antiphotoaging effect on the UVB-irradiated HaCaT photoaged cell model in a dose-dependent manner. WNLNP exerted its protective effect mainly through inhibiting ROS production, decreasing MMP-1 expression, but increasing extracellular pro-collagen I content. Furthermore, WNLNP downregulated p38, JNK, ERK, and p65 phosphorylation in the MAPK/NF-κB signaling pathway and attenuated bax over-expressions but reversed bcl-2 reduction in UVB- irradiated HaCaT cells. The molecular docking analysis showed that WNLNP forms five and seven hydrogen bonds with NF-κB (p65) and MMP-1, respectively. This study suggested that a pentapeptide WNLNP isolated from OPEH had great potential to prevent and regulate skin photoaging.

The development of new approaches to prevent microbial surface adhesion and biofilm formation is an emerging need following the growing understanding of the impact of biofilm-related infections on human health. Staphylococcus epidermidis, with its ability to form biofilm and colonize biomaterials, represents the most frequent causative agent involved in infections of medical devices. In the research of new anti-biofilm agents against S. epidermidis biofilm, Antarctic marine bacteria represent an untapped reservoir of biodiversity. In the present study, the attention was focused on Psychrobacter sp. TAE2020, an Antarctic marine bacterium that produces molecules able to impair the initial attachment of S. epidermidis strains to the polystyrene surface. The setup of suitable purification protocols allowed the identification by NMR spectroscopy and LC-MS/MS analysis of a protein-polysaccharide complex named CATASAN. This complex proved to be a very effective anti-biofilm agent. Indeed, it not only interferes with cell surface attachment, but also prevents biofilm formation and affects the mature biofilm matrix structure of S. epidermidis. Moreover, CATASAN is endowed with a good emulsification activity in a wide range of pH and temperature. Therefore, its use can be easily extended to different biotechnological applications.

Phlorotannins are a type of natural active substance extracted from brown algae, which belong to a type of important plant polyphenol. Phloroglucinol is the basic unit in its structure. Phlorotannins have a wide range of biological activities, such as antioxidant, antibacterial, antiviral, anti-tumor, anti-hypertensive, hypoglycemic, whitening, anti-allergic and anti-inflammatory, etc. Phlorotannins are mainly used in the fields of medicine, food and cosmetics. This paper reviews the research progress of extraction, separation technology and biological activity of phlorotannins, which will help the scientific community investigate the greater biological significance of phlorotannins.

Alginate hydrogels have been broadly investigated for use in medical applications due to their biocompatibility and the possibility to encapsulate cells, proteins, and drugs. In the treatment of peritoneal metastasis, rapid drug clearance from the peritoneal cavity is a major challenge. Aiming to delay drug absorption and reduce toxic side effects, cabazitaxel (CAB)-loaded poly(alkyl cyanoacrylate) (PACA) nanoparticles were encapsulated in alginate microspheres. The PACAlg alginate microspheres were synthesized by electrostatic droplet generation and the physicochemical properties, stability, drug release kinetics, and mesothelial cytotoxicity were analyzed before biodistribution and therapeutic efficacy were studied in mice. The 450 µm microspheres were stable at in vivo conditions for at least 21 days after intraperitoneal implantation in mice, and distributed evenly throughout the peritoneal cavity without aggregation or adhesion. The nanoparticles were stably retained in the alginate microspheres, and nanoparticle toxicity to mesothelial cells was reduced, while the therapeutic efficacy of free CAB was maintained or improved in vivo. Altogether, this work presents the alginate encapsulation of drug-loaded nanoparticles as a promising novel strategy for the treatment of peritoneal metastasis that can improve the therapeutic ratio between toxicity and therapeutic efficacy.

Big defensins are two-domain antimicrobial peptides (AMPs) that have highly diversified in mollusks. Cg-BigDefs are expressed by immune cells in the oyster Crassostrea gigas, and their expression is dampened during the Pacific Oyster Mortality Syndrome (POMS), which evolves toward fatal bacteremia. We evaluated whether Cg-BigDefs contribute to the control of oyster-associated microbial communities. Two Cg-BigDefs that are representative of molecular diversity within the peptide family, namely Cg-BigDef1 and Cg-BigDef5, were characterized by gene cloning and synthesized by solid-phase peptide synthesis and native chemical ligation. Synthetic peptides were tested for antibacterial activity against a collection of culturable bacteria belonging to the oyster microbiota, characterized by 16S sequencing and MALDI Biotyping. We first tested the potential of Cg-BigDefs to control the oyster microbiota by injecting synthetic Cg-BigDef1 into oyster tissues and analyzing microbiota dynamics over 24 h by 16S metabarcoding. Cg-BigDef1 induced a significant shift in oyster microbiota β-diversity after 6 h and 24 h, prompting us to investigate antimicrobial activities in vitro against members of the oyster microbiota. Both Cg-BigDef1 and Cg-BigDef5 were active at a high salt concentration (400 mM NaCl) and showed broad spectra of activity against bacteria associated with C. gigas pathologies. Antimicrobial specificity was observed for both molecules at an intra- and inter-genera level. Remarkably, antimicrobial spectra of Cg-BigDef1 and Cg-BigDef5 were complementary, and peptides acted synergistically. Overall, we found that primary sequence diversification of Cg-BigDefs has generated specificity and synergy and extended the spectrum of activity of this peptide family.

Ocean acidification (OA) is a dramatic perturbation of seawater environments due to increasing anthropogenic emissions of CO2. Several studies indicated that OA frequently induces marine biota stress and a reduction of biodiversity. Here, we adopted the macroalga Ulva prolifera as a model and applied a complementary multi-omics approach to investigate the metabolic profiles under normal and acidified conditions. Our results show that U. prolifera grows at higher rates in acidified environments. Consistently, we observed lower sucrose and phosphocreatine concentrations in response to a higher demand of energy for growth and a higher availability of essential amino acids, likely related to increased protein biosynthesis. In addition, pathways leading to signaling and deterrent compounds appeared perturbed. Finally, a remarkable shift was observed here for the first time in the fatty acid composition of triglycerides, with a decrease in the relative abundance of PUFAs towards an appreciable increase of palmitic acid, thus suggesting a remodeling in lipid biosynthesis. Overall, our studies revealed modulation of several biosynthetic pathways under OA conditions in which, besides the possible effects on the marine ecosystem, the metabolic changes of the alga should be taken into account considering its potential nutraceutical applications.

Alginate is abundant in the cell walls of brown algae. Alginate lyases can degrade alginate, and thus play an important role in the marine carbon cycle and industrial production. Currently, most reported alginate lyases contain only one functional alginate lyase domain. AlyC8 is a putative alginate lyase with two alginate lyase domains (CD1 and CD2) from the marine alginate-degrading strain Vibrio sp. C42. To characterize AlyC8 and its two catalytic domains, AlyC8 and its two catalytic domain-deleted mutants, AlyC8-CD1 and AlyC8-CD2, were expressed in Escherichia coli. All three proteins have noticeable activity toward sodium alginate and exhibit optimal activities at pH 8.0-9.0 and at 30-40 °C, demonstrating that both CD1 and CD2 are functional. However, CD1 and CD2 showed opposite substrate specificity. The differences in substrate specificity and degradation products of alginate between the mutants and AlyC8 demonstrate that CD1 and CD2 can act synergistically to enable AlyC8 to degrade various alginate substrates into smaller oligomeric products. Moreover, kinetic analysis indicated that AlyC8-CD1 plays a major role in the degradation of alginate by AlyC8. These results demonstrate that AlyC8 is a novel alginate lyase with two functional catalytic domains that are synergistic in alginate degradation, which is helpful for a better understanding of alginate lyases and alginate degradation.

Pimprinine and streptochlorin are indole alkaloids derived from marine or soil microorganisms. In our previous study, they were promising lead compounds due to their potent bioactivity in preventing many phytopathogens, but further structural modifications are required to improve their antifungal activity. In this study, pimprinine and streptochlorin were used as parent structures with the combination strategy of their structural features. Three series of target compounds were designed and synthesized. Subsequent evaluation for antifungal activity against six common phytopathogenic fungi showed that some of thee compounds possessed excellent effects, and this is highlighted by compounds 4a and 5a, displaying 99.9% growth inhibition against Gibberella zeae and Alternaria Leaf Spot under 50 μg/mL, respectively. EC50 values indicated that compounds 4a, 5a, 8c, and 8d were even more active than Azoxystrobin and Boscalid. SAR analysis revealed the relationship between 5-(3'-indolyl)oxazole scaffold and antifungal activity, which provides useful insight into the development of new target molecules. Molecular docking models indicate that compound 4a binds with leucyl-tRNA synthetase in a similar mode as AN2690, offering a perspective on the mode of action for the study of its antifungal activity. These results suggest that compounds 4a and 5a could be regarded as novel and promising antifungal agents against phytopathogens due to their valuable potency.

This study performed the extraction of gelatin from saithe (Pollachius virens) skin and compared it to commercial marine gelatin. As a first stage, we investigated the physicochemical and biochemical properties of the gelatin. SDS-PAGE analysis revealed the presence of α-chains, β-chains, and other high-molecular-weight aggregates. DSC thermograms showed typical gelatin behavior, while the FTIR spectra were mainly situated in the amide band region (amide A, amide B, amide I, amide II, and amide III). In the second stage, we produced O/W emulsions and analyzed their physical and oxidative stability over 9 days. Oil droplets stabilized with the gelatins obtained from saithe fish skin had a size of ~500 nm and a ζ-potential ~+25 mV, which is comparable to oil droplets stabilized with commercial gelatin products. Moreover, the oxidative stability of the emulsions stabilized with gelatin from saithe fish skin showed promising results in terms of preventing the formation of some volatile compounds towards the end of the storage period compared to when using the commercial gelatins. This study indicates the potential application of fish skin gelatin in the fields of food and cosmetics, as well as suggesting that further investigations of their techno-functional properties.

Two new guanidine alkaloids, batzelladines O (1) and P (2), were isolated from the deep-water marine sponge Monanchora pulchra. The structures of these metabolites were determined by NMR spectroscopy, mass spectrometry, and ECD. The isolated compounds exhibited cytotoxic activity in human prostate cancer cells PC3, PC3-DR, and 22Rv1 at low micromolar concentrations and inhibited colony formation and survival of the cancer cells. Batzelladines O (1) and P (2) induced apoptosis, which was detected by Western blotting as caspase-3 and PARP cleavage. Additionally, induction of pro-survival autophagy indicated as upregulation of LC3B-II and suppression of mTOR was observed in the treated cells. In line with this, the combination with autophagy inhibitor 3-methyladenine synergistically increased the cytotoxic activity of batzelladines O (1) and P (2). Both compounds were equally active in docetaxel-sensitive and docetaxel-resistant prostate cancer cells, despite exhibiting a slight p-glycoprotein substrate-like activity. In combination with docetaxel, an additive effect was observed. In conclusion, the isolated new guanidine alkaloids are promising drug candidates for the treatment of taxane-resistant prostate cancer.

The carrageenans isolated from red algae demonstrated a variety of activities from antiviral and immunomodulatory to antitumor. The diverse structure and sulfation profile of carrageenans provide a great landscape for drug development. In this study, we isolated, purified and structurally characterized κo- and λo- oligosaccharides from the marine algae Chondrus armatus. We further examined the tumor suppressive activity of both carrageenans in gastrointestinal cancer models. Thus, using MTT assay, we could demonstrate a pronounced antiproliferative effect of the carrageenans in KYSE-30 and FLO-1 as well as HCT-116 and RKO cell lines with IC50 184~405 μg/mL, while both compounds were less active in non-cancer epithelial cells RPE-1. This effect was stipulated by the inhibition of cell cycle progression in the cancer cells. Specifically, flow cytometry revealed an S phase delay in FLO-1 and HCT-116 cells under κo-carrageenan treatment, while KYSE-30 demonstrated a pronounced G2/M cell cycle delay. In line with this, western blotting revealed a reduction of cell cycle markers CDK2 and E2F2. Interestingly, κo-carrageenan inhibited cell cycle progression of RKO cells in G1 phase. Finally, isolated κo- and λo- carrageenans induced apoptosis on adenocarcinomas, specifically with high apoptosis induction in RKO cells. Overall, our data underline the potential of κo- and λo- carrageenans for colon and esophageal carcinoma drug development.

The market demand for marine-based cosmetics has shown a tremendous growth rate in the last decade. Marine resources represent a promising source of novel bioactive compounds for new cosmetic ingredient development. However, concern about sustainability also becomes an issue that should be considered in developing cosmetic ingredients. The fisheries industry (e.g., fishing, farming, and processing) generates large amounts of leftovers containing valuable substances, which are potent sources of cosmeceutical ingredients. Several bioactive substances could be extracted from the marine by-product that can be utilized as a potent ingredient to develop cosmetics products. Those bioactive substances (e.g., collagen from fish waste and chitin from crustacean waste) could be utilized as anti-photoaging, anti-wrinkle, skin barrier, and hair care products. From this perspective, this review aims to approach the potential active ingredients derived from marine by-products for cosmetics and discuss the possible activity of those active ingredients in promoting human beauty. In addition, this review also covers the prospect and challenge of using marine by-products toward the emerging concept of sustainable blue cosmetics.

Six new citreoviridins (citreoviridins J-O, 1-6) and twenty-two known compounds (7-28) were isolated from the deep-sea-derived Penicillium citreonigrum MCCC 3A00169. The structures of the new compounds were determined by spectroscopic methods, including the HRESIMS, NMR, ECD calculations, and dimolybdenum tetraacetate-induced CD (ICD) experiments. Citreoviridins J-O (1-6) are diastereomers of 6,7-epoxycitreoviridin with different chiral centers at C-2-C-7. Pyrenocine A (7), terrein (14), and citreoviridin (20) significantly induced apoptosis for HeLa cells with IC50 values of 5.4 μM, 11.3 μM, and 0.7 μM, respectively. To be specific, pyrenocine A could induce S phase arrest, while terrein and citreoviridin could obviously induce G0-G1 phase arrest. Citreoviridin could inhibit mTOR activity in HeLa cells.

A novel carotenoid with a unique 2,6-cyclo-ψ-end group, named roretziaxanthin (1), was isolated from the sea squirt Halocynthia roretzi as a minor carotenoid along with (3S,3'S)-astaxanthin, alloxanthin, halocynthiaxanthin, mytiloxanthin, mytiloxanthinone, etc. This structure was determined to be 3-hydroxy-1',16'-didehydro-1',2'-dihydro-2',6'-cyclo-β,ψ-carotene-4,4'-dione by UV-VIS, MS, and NMR spectral data. The formation mechanism of roretziaxanthin in the sea squirt was discussed.

The frequent occurrence of marine dinoflagellates producing palytoxin (PLTX) or okadaic acid (OA) raises concern for the possible co-presence of these toxins in seafood, leading to additive or synergistic adverse effects in consumers. Thus, the acute oral toxicity of PLTX and OA association was evaluated in mice: groups of eight female CD-1 mice were administered by gavage with combined doses of PLTX (30, 90 or 270 μg/kg) and OA (370 μg/kg), or with each individual toxin, recording signs up to 24 h (five mice) and 14 days (three mice). Lethal effects occurred only after PLTX (90 or 270 μg/kg) exposure, alone or combined with OA, also during the 14-day recovery. PLTX induced scratching, piloerection, abdominal swelling, muscle spasms, paralysis and dyspnea, which increased in frequency or duration when co-administered with OA. The latter induced only diarrhea. At 24 h, PLTX (90 or 270 μg/kg) and OA caused wall redness in the small intestine or pale fluid accumulation in its lumen, respectively. These effects co-occurred in mice co-exposed to PLTX (90 or 270 μg/kg) and OA, and were associated with slight ulcers and inflammation at forestomach. PLTX (270 μg/kg alone or 90 μg/kg associated with OA) also decreased the liver/body weight ratio, reducing hepatocyte glycogen (270 μg/kg, alone or combined with OA). No alterations were recorded in surviving mice after 14 days. Overall, the study suggests additive effects of PLTX and OA that should be considered for their risk assessment as seafood contaminants.

Nannochloropsis oculata is well-recognized as a potential microalgal source of valuable compounds such as polyunsaturated fatty acids, particularly, eicosapentaenoic acid (EPA). The content and profile of these lipids is highly dependent on the growth conditions and can, therefore, be tailored through modulation of the growth parameters, specifically, temperature. Moreover, biological activities are composition dependent. In the present work, lipid extracts obtained from N. oculata, grown under constant temperature and under modulated temperature stress (to increase EPA content; Str) were characterized by GC-FID and several bioactivities were evaluated, namely, antioxidant (L-ORACFL), cytotoxic (MTT), adipolytic, anti-hepatic lipid accumulation (steatosis), and anti-inflammatory properties. Both extracts exhibited antioxidant activity (c.a. 49 µmol Troloxequivalent/mgextract) and the absence of toxicity (up to 800 µg/mL) toward colon and hepatic cells, adipocytes, and macrophages. They also induced adipolysis and the inhibition of triglycerides hepatic accumulation, with a higher impact from Str. In addition, anti-inflammatory activity was observed in the lipopolysaccharide-induced inflammation of macrophages in the presence of either extract, since lower levels of pro-inflammatory interleukin-6 and interferon-β were obtained, specifically by Str. The results presented herein revealed that modulated temperature stress may enhance the health effects of N. oculata lipid extracts, which may be safely utilized to formulate novel food products.

The controlled-release characteristic of drug delivery systems is utilized to increase the residence time of therapeutic agents in the human body. This study aimed to formulate and characterize salsalate (SSL)-loaded chitosan nanoparticles (CSNPs) prepared using the ionic gelation method and to assess their in vitro release and antibacterial and antibiofilm activities. The optimized CSNPs and CSNP-SSL formulation were characterized for particle size (156.4 ± 12.7 nm and 132.8 ± 17.4 nm), polydispersity index (0.489 ± 0.011 and 0.236 ± 132 0.021), zeta potential (68 ± 16 mV and 37 ± 11 mV), and entrapment efficiency (68.9 ± 2.14%). Physicochemical features of these nanoparticles were characterized using UV-visible and Fourier transform infrared spectroscopy and X-ray diffraction pattern. Scanning electron microscopy studies indicated that CSNPs and CSNP-SSL were spherical in shape with a smooth surface and their particle size ranged between 200 and 500 nm. In vitro release profiles of the optimized formulations showed an initial burst followed by slow and sustained drug release after 18 h (64.2 ± 3.2%) and 48 h (84.6 ± 4.23%), respectively. Additionally, the CSNPs and CSNP-SSL nanoparticles showed a sustained antibacterial action against Staphylococcus aureus (15.7 ± 0.1 and 19.1 ± 1.2 mm) and Escherichia coli (17.5 ± 0.8 and 21.6 ± 1.7 243 mm). Interestingly, CSNP-SSL showed better capability (89.4 ± 1.2% and 95.8 ± 0.7%) than did CSNPs in inhibiting antibiofilm production by Enterobacter tabaci (E2) and Klebsiella quasipneumoniae (SC3). Therefore, CSNPs are a promising dosage form for sustained drug delivery and enhanced antibacterial and antibiofilm activity of SSL; these results could be translated into increased patient compliance.

Sea anemones are predatory marine invertebrates and have diverse venom arsenals. Venom is integral to their biology, and is used in competition, defense, and feeding. Three lineages of sea anemones are known to have independently evolved symbiotic relationships with clownfish, however the evolutionary impact of this relationship on the venom composition of the host is still unknown. Here, we investigate the potential of this symbiotic relationship to shape the venom profiles of the sea anemones that host clownfish. We use transcriptomic data to identify differences and similarities in venom profiles of six sea anemone species, representing the three known clades of clownfish-hosting sea anemones. We recovered 1121 transcripts matching verified toxins across all species, and show that hemolytic and hemorrhagic toxins are consistently the most dominant and diverse toxins across all species examined. These results are consistent with the known biology of sea anemones, provide foundational data on venom diversity of these species, and allow for a review of existing hierarchical structures in venomic studies.

Diabolican, or HE800, is an exopolysaccharide secreted by the non-pathogenic Gram-negative marine bacterium Vibrio diabolicus (CNCM I-1629). This polysaccharide was enzymatically degraded by the Bacteroides cellulosilyticus WH2 hyaluronan lyase. The end products were purified by size-exclusion chromatography and their structures were analyzed in depth by nuclear magnetic resonance (NMR). The oligosaccharide structures confirmed the possible site of cleavage of the enzyme showing plasticity in the substrate recognitions. The production of glycosaminoglycan-mimetic oligosaccharides of defined molecular weight and structure opens new perspectives in the valorization of the marine polysaccharide diabolican.

Post-menopausal dry mouth or xerostomia is caused by reduced salivary secretion. This study aimed to investigate the efficacy of echinochrome A (Ech A) in alleviating submandibular gland dysfunctions in ovariectomized rats that mimic menopause. Female rats that were eight-weeks-old were randomly divided into SHAM-6, -12; OVX-6, -12; and ECH-6, -12 groups (consisting of 6- and 12-weeks post-sham-operated, ovariectomized, and Ech A-treated ovariectomized rats, respectively). The ECH groups had lower body weight than OVX but similar food intake and estradiol or estrogen receptor β expression. However, the ECH groups had lower mRNA expression of sterol-regulatory element binding protein-1c (Srebp-1c), acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), cluster of differentiation 36 (Cd36), and lipid vacuole deposition than OVX mice. Moreover, reactive oxygen species (ROS), malondialdehyde (MDA), and iron accumulation were lower in the ECH than in the OVX groups. Fibrosis markers, transforming growth factor β (Tgf-βI and Tgf-βII mRNA) increased in the OVX than SHAM groups but decreased in the ECH groups. Aquaporin (Aqp-1 and Aqp-5 mRNA) and mucin expressions were downregulated in the OVX groups but improved with Ech A. In addition, Ech A prevented post-menopausal salivary gland dysfunction by inhibiting lipogenesis and ferroptosis. These findings suggest Ech A as an effective remedy for treating menopausal dry mouth.

Biofilms, responsible for many serious drawbacks in the medical and marine environment, can grow on abiotic and biotic surfaces. Commercial anti-biofilm solutions, based on the use of biocides, are available but their use increases the risk of antibiotic resistance and environmental pollution in marine industries. There is an urgent need to work on the development of ecofriendly solutions, formulated without biocidal agents, that rely on the anti-adhesive physico-chemical properties of their materials. In this context, exopolysaccharides (EPSs) are natural biopolymers with complex properties than may be used as anti-adhesive agents. This study is focused on the effect of the EPS MO245, a hyaluronic acid-like polysaccharide, on the growth, adhesion, biofilm maturation, and dispersion of two pathogenic model strains, Pseudomonas aeruginosa sp. PaO1 and Vibrio harveyi DSM19623. Our results demonstrated that MO245 may limit biofilm formation, with a biofilm inhibition between 20 and 50%, without any biocidal activity. Since EPSs have no significant impact on the bacterial motility and quorum sensing factors, our results indicate that physico-chemical interactions between the bacteria and the surfaces are modified due to the presence of an adsorbed EPS layer acting as a non-adsorbing layer.

Osmolytes are naturally occurring organic compounds that protect cells against various forms of stress. Highly polar, zwitterionic osmolytes are often used by marine algae and bacteria to counteract salinity or temperature stress. We investigated the effect of several stress conditions including different salinities, temperatures, and exposure to organic metabolites released by the alga Tetraselmis striata on the halophilic heterotrophic bacterium Pelagibaca bermudensis. Using ultra-high-performance liquid chromatography (UHPLC) on a ZIC-HILIC column and high-resolution electrospray ionization mass spectrometry, we simultaneously detected and quantified the eleven highly polar compounds dimethylsulfoxonium propionate (DMSOP), dimethylsulfoniopropionate (DMSP), gonyol, cysteinolic acid, ectoine, glycine betaine (GBT), carnitine, sarcosine, choline, proline, and 4-hydroxyproline. All compounds are newly described in P. bermudensis and potentially involved in physiological functions essential for bacterial survival under variable environmental conditions. We report that adaptation to various forms of stress is accomplished by adjusting the pattern and amount of the zwitterionic metabolites.

A chemical investigation of a methanol extract of Spongia sp., a marine sponge collected from the Philippines, identified 12 unreported scalarane-type alkaloids-scalimides A-L (1-12)-together with two previously described scalarin derivatives. The elucidation of the structure of the scalaranes based on the interpretation of their NMR and HRMS data revealed that 1-12 featured a β-alanine-substituted E-ring but differed from each other through variations in their oxidation states and substitutions occurring at C16, C24, and C25. Evaluation of the antimicrobial activity of 1-12 against several Gram-positive and Gram-negative bacteria showed that 10 and 11 were active against Micrococcus luteus and Bacillus subtilis, respectively, with MIC values ranging from 4 to 16 μg/mL.

Multiple animal species have evolved resistance to the neurotoxin tetrodotoxin (TTX) through changes in voltage-gated sodium ion channels (VGSCs). Amino acid substitutions in TTX-resistant lineages appear to be positionally convergent with changes in homologous residues associated with reductions in TTX block. We used homology modeling coupled with docking simulations to test whether positionally convergent substitutions generate functional convergence at the level of TTX-channel interactions. We found little evidence that amino acids at convergent positions generated similar patterns among TTX-resistant animal lineages across several metrics, including number of polar contacts, polar contact position, and estimates of binding energy. Though binding energy values calculated for TTX docking were reduced for some TTX-resistant channels, not all TTX-resistant channels and not all of our analyses returned reduced binding energy values for TTX-resistant channels. Our results do not support a simple model of toxin resistance where a reduced number of bonds between TTX and the channel protein prevents blocking. Rather models that incorporate flexibility and movement of the protein overall may better describe how homologous substitutions in the channel cause changes in TTX block.

Magnetotactic bacteria (MTB) produce magnetosomes, which are membrane-embedded magnetic nanoparticles. Despite their technological applicability, the production of magnetite magnetosomes depends on the cultivation of MTB, which results in low yields. Thus, strategies for the large-scale cultivation of MTB need to be improved. Here, we describe a new approach for bioreactor cultivation of Magnetovibrio blakemorei strain MV-1T. Firstly, a fed-batch with a supplementation of iron source and N2O injection in 24-h pulses was established. After 120 h of cultivation, the production of magnetite reached 24.5 mg∙L-1. The maximum productivity (16.8 mg∙L-1∙day-1) was reached between 48 and 72 h. However, the productivity and mean number of magnetosomes per cell decreased after 72 h. Therefore, continuous culture in the chemostat was established. In the continuous process, magnetite production and productivity were 27.1 mg∙L-1 and 22.7 mg∙L-1∙day-1, respectively, at 120 h. This new approach prevented a decrease in magnetite production in comparison to the fed-batch strategy.

Neoagaro-oligosaccharides (NAOs) belong to the algae oligosaccharides. NAOs have been found to have diverse biological activities. However, the effects of NAOs on depression and their underlying mechanism have not been thoroughly studied. A chronic restraint stress (CRS)-induced C57BL/6J mouse model was used to assess the antidepressant effects of NAOs. Anxiety and depression behaviors were assessed by open field tests (OFT) and forced swimming tests (FST), while interleukin 18 (IL-18), 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) were the molecular biomarkers of depression. Fecal microbiota transplantation (FMT) was performed. The results showed that NAO treatment significantly improved the body weight of depressed mice and reduced the central area time in the OFT and immobility time in the FST. NAO treatment decreased the levels of IL-18 in the serum and increased the levels of 5-HT in the serum and whole brain and of BDNF in the whole brain. NAO treatment mitigated the gut microbiota dysbiosis in the depressed mice and reversed the decreased levels of short-chain fatty acids (SCFAs) in the cecum of the depressed mice. FMT indicated that the gut microbiota is, indeed, linked to depression, which was reflected in the changes in weight gain and behaviors. In a word, NAOs effectively reversed the CRS-induced mice model of depression, which depended on the changes in the gut microbiota and SCFAs, as well as its modulation of 5-HT and BDNF.

Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread metalloenzymes in organisms in all life kingdoms, being involved in pH regulation, metabolic processes and many other physiological and pathological conditions. CA inhibitors and activators thus possess applications as pharmacological agents in the management of a range of diseases. Marine natural products have allowed the identification of some highly interesting CA inhibitors, among which are sulfonamides, phenols, polyamines, coumarins and several other miscellaneous inhibitors, which are reviewed here. Psammaplin C and some bromophenols were the most investigated classes of such marine-based inhibitors and have been used as lead molecules for developing interesting types of potent and, in some cases, isoform-selective inhibitors, with applications as antitumor agents by inhibiting human CA XII and P-glycoprotein activities. Some phenols have shown interesting bacterial and fungal β-CA inhibitory effects. Marine natural products thus constitute a gold mine for identifying novel CA inhibitors, some of which may lead to the development of novel types of pharmacological agents.

We aimed to observe the effects of Echinochrome A (Ech A) on systemic changes using a rat model of preeclampsia. The results showed that an infusion of angiotensin II (Ang II) through an osmotic pump (1 μg/kg/min) on GD 8 increased systolic and diastolic blood pressures and reduced fetal weight and placental weight. The diameters of the glomeruli were expended and glomeruli capillaries were diminished. No change was observed in the heart and liver in the Ang II group, but epithelial structures were disrupted in the uterus. Ech A treatment on GD 14 (100 μg/μL) through the jugular vein reduced systolic and diastolic blood pressures and reversed glomerulus alterations, but the fetal or placental parameters were unaffected. Ech A only partly reversed the effect on the uterus. The mRNA expression of TNF-α was increased and IL-10 and VEGF were reduced in the uterus of the Ang II group, while Ech A restored these changes. A similar trend was observed in the kidney, liver, and heart of this group. Furthermore, Bcl-2 was reduced and Bcl-2/Bax ratios were significantly reduced in the kidney and heart of the Ang II group, while Ech A reversed these changes. We suggest that Ech A modulates inflammation and apoptosis in key systemic organs in Ang II-induced rat preeclampsia and preserves kidney and uterus structures and reduces blood pressure.

Marine fungi-derived secondary metabolites are still an important source for the discovery of potential antimicrobial agents. Here, five new polyketides (1, 2, and 6-8) and seven known compounds (3-5 and 9-12) were obtained from the culture of the marine-derived fungus Trichoderma sp. JWM29-10-1. Their structures were identified by extensive spectrographic data analyses, including 1D and 2D NMR, UV, IR, and HR-ESI-MS. Further, the absolute configurations of new compounds were determined by circular dichroism (CD) spectrum and alkali-hydrolysis in combination with the in situ dimolybdenum CD method. Subsequently, the antimicrobial effects of these isolated compounds were assessed by examining the minimal inhibition concentration (MIC) with the broth microdilution assay. Compounds 1 and 2 exhibited potent antimicrobial activity against Helicobacter pylori, including multidrug-resistant strains, with MIC range values of 2-8 µg/mL. Moreover, compound 1 showed significant inhibitory effects on the growth of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and vancomycin-resistant Enterococcus faecium, which greatly threaten human health. This study demonstrates that chromone derivatives 1-2, especially for 1, could be potential lead compounds for the development of new antimicrobial agents and provides insight for future medicinal chemistry research.

Low molecular weight (<5 kDa) peptides from mussels (Mytilus edulis) (MPs) and the peptides from clams (Ruditapes philippinarum) (CPs) were prepared through enzymatic hydrolysis by proteases (dispase, pepsin, trypsin, alcalase and papain). Both the MPs and the CPs showed excellent in vitro scavenging ability of free radicals including OH, DPPH and ABTS in the concentration range of 0.625-10.000 mg/mL. By contrast, the MPs hydrolyzed by alcalase (MPs-A) and the CPs hydrolyzed by dispase (CPs-D) had the highest antioxidant activities. Furthermore, MPs-A and CPs-D exhibited protective capabilities against oxidative damage induced by H2O2 in HepG2 cells in the concentration range of 25-800 μg/mL. Meanwhile, compared with the corresponding indicators of the negative control (alcohol-fed) mice, lower contents of hepatic MDA and serums ALT and AST, as well as higher activities of hepatic SOD and GSH-PX were observed in experiment mice treated with MPs-A and CPs-D. The present results clearly indicated that Mytilus edulis and Ruditapes philippinarum are good sources of hepatoprotective peptides.

Ocean resources are a priceless repository of unique species and bioactive compounds with denouement properties that can be used in the fabrication of advanced biomaterials as new templates for supporting the cell culture envisaging tissue engineering approaches. The collagen of marine origin can be sustainably isolated from the underrated fish processing industry by-products, while silica and related materials can be found in the spicules of marine sponges and diatoms frustules. Aiming to address the potential of biomaterials composed from marine collagen and silica-based materials in the context of bone regeneration, four different 3D porous structure formulations (COL, COL:BG, COL:D.E, and COL:BS) were fabricated by freeze-drying. The skins of Atlantic cod (Gadus morhua) were used as raw materials for the collagen (COL) isolation, which was successfully characterized by SDS-PAGE, FTIR, CD, and amino acid analyses, and identified as a type I collagen, produced with a 1.5% yield and a preserved characteristic triple helix conformation. Bioactive glass 45S5 bioglass® (BG), diatomaceous earth (D.E.) powder, and biosilica (BS) isolated from the Axinella infundibuliformis sponge were chosen as silica-based materials, which were obtained as microparticles and characterized by distinct morphological features. The biomaterials revealed microporous structures, showing a porosity higher than 85%, a mean pore size range of 138-315 μm depending on their composition, with 70% interconnectivity which can be favorable for cell migration and ensure the needed nutrient supply. In vitro, biological assays were conducted by culturing L929 fibroblast-like cells, which confirmed not only the non-toxic nature of the developed biomaterials but also their capability to support cell adhesion and proliferation, particularly the COL:BS biomaterials, as observed by calcein-AM staining upon seven days of culture. Moreover, phalloidin and DAPI staining revealed well-spread cells, populating the entire construct. This study established marine collagen/silica biocomposites as potential scaffolds for tissue engineering, setting the basis for future studies, particularly envisaging the regeneration of non-load-bearing bone tissues.

Polybius henslowii, an abundant yet unexploited species of swimming crab, was investigated as a potential source of α-chitin and calcium lactate using deep eutectic solvents (DES) as extracting solvents. Choline chloride-malonic acid (CCMA) and choline chloride-lactic acid (CCLA) were used to obtain high purity α-chitin from ball-milled P. henslowii exoskeleton in 2 h at 120 °C, with yields of 12.05 ± 2.54% and 12.8 ± 1.54%, respectively. The physical and chemical characteristics of the obtained chitins were assessed using CHN elemental analysis, attenuated total reflectance-Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Furthermore, the CCLA solvent was reusable three times with little effect on the extract purity, and calcium lactate was produced at the end of the recycling cycles. The ensuing calcium lactate was also characterized in terms of chemical and physical properties. The obtained chitin is a promising raw material for downstream processing and the double valorization pathway with the obtention of calcium salts may increase the viability of a DES-based approach for the processing of mineralized substrates.

The aim of this study was to evaluate the effects of fucoidan isolated from C. crinita on histamine-induced paw inflammation in rats, and on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 in rats during systemic inflammation response. The levels of TNF-α in a model of acute peritonitis in rats were also investigated. The isolated crude fucoidan was identified as a sulfated xylogalactofucan with high, medium, and low molecular weight fractions and a content of fucose of 39.74%, xylose of 20.75%, and galactose of 15.51%. Fucoidan from C. crinita showed better anti-inflammatory effects in the rat paw edema model, and this effect was present during all stages of the experiment. When compared to controls, a commercial fucoidan from F. vesiculosus, the results also displayed anti-inflammatory activity on the 60th, 90th, and 120th minute of the experiment. A significant decrease in serum levels of IL-1β in rats treated with both doses of C. crinita fucoidan was observed in comparison to controls, whereas TNF-α concentrations were reduced only in the group treated with fucoidan from C. crinita at the dose of 25 mg/kg bw. In the model of carrageenan-induced peritonitis, we observed a tendency of decrease in the levels of the pro-inflammatory cytokine TNF-α in peritoneal fluid after a single dose of C. crinita fucoidan, but this did not reach the statistical significance margin. Single doses of C. crinita fucoidan did not alter serum levels of the anti-inflammatory cytokine IL-10 in animals with lipopolysaccharide-induced systemic inflammation.

Dietary supplements that promote healthy aging are mostly warranted in an aging society. Because of age-related risks, anti-inflammatory and anti-oxidative agents such as microalgae are potential candidates for intervention. In a randomized controlled trial, we tested Phaeodactylum tricornutum (PT), a microalgae rich in eicosapentaenoic acid (EPA), carotenoids, vitamins, and β-glucans, cultured in bioreactors. In this pilot trial, 19 healthy elderly received supplements for two weeks based on either the whole PT (A), the β-1,3-glucan-rich PT supernatant (SupB), the combination thereof (A+SupB), or a Comparator product (Comp). The primary outcome variable plasma interleukin-6 was reduced after treatment with A+SupB compared to the Comp group (p = 0.04). The mobility parameters 5 s sit-to-stand test (p = 0.04 in the A group) and by trend gait speed (p = 0.08 in the A+SupB diet) were improved compared to Comp. No treatment effects were observed for fatty acids, compared to Comp but omega-6 to -3 fatty acid ratio (p = 0.006) and arachidonic acid/EPA ratio (p = 0.006) were reduced within group A+SupB. Further, the SupB study product reduced faecal zonulin (p = 0.03) compared to the Comp. The data revealed an anti-inflammatory and potentially anti-oxidative effect of particular PT preparations, suggesting that they might be suitable for effects in healthy elderly.

The diverse therapeutic feasibility of the sea urchin-derived naphthoquinone pigment, Echinochrome A (Ech A), has been studied. Simple and noninvasive administration routes should be explored, to obtain the feasibility. Although the therapeutic potential has been proven through several preclinical studies, the biosafety of orally administered Ech A and its direct influence on intestinal cells have not been evaluated. To estimate the bioavailability of Ech A as an oral administration drug, small intestinal and colonic epithelial organoids were developed from mice and humans. The morphology and cellular composition of intestinal organoids were evaluated after Ech A treatment. Ech A treatment significantly increased the expression of LGR5 (~2.38-fold change, p = 0.009) and MUC2 (~1.85-fold change, p = 0.08). Notably, in the presence of oxidative stress, Ech A attenuated oxidative stress up to 1.8-fold (p = 0.04), with a restored gene expression of LGR5 (~4.11-fold change, p = 0.0004), as well as an increased expression of Ly6a (~3.51-fold change, p = 0.005) and CLU (~2.5-fold change, p = 0.01), markers of revival stem cells. In conclusion, Ech A is harmless to intestinal tissues; rather, it promotes the maintenance and regeneration of the intestinal epithelium, suggesting possible beneficial effects on the intestine when used as an oral medication.

Novel high-throughput cultivation techniques create a demand to pre-select strains for in-depth follow-up studies. We report a workflow to identify promising producers of novel natural products by systematically characterizing their metabolomes. For this purpose, 60 strains from four phyla (Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes) comprising 16 novel species and six novel genera were cultivated from marine and terrestrial sources. Their cellular metabolomes were recorded by LC-MS/MS; data analysis comprised databases MS/MS matching, in silico compound assignment, and GNPS-based molecular networking. Overall, 1052 different molecules were identified from 6418 features, among them were unusual metabolites such as 4-methoxychalcone. Only a minor portion of the 755 features were found in all phyla, while the majority occurred in a single phylogroup or even in a single strain. Metabolomic methods enabled the recognition of highly talented strains such as AEG42_45, which had 107 unique features, among which a family of 28 potentially novel and related compounds according to MS/MS similarities. In summary, we propose that high-throughput cultivation and isolation of bacteria in combination with the presented systematic and unbiased metabolome analysis workflow is a promising approach to capture and assess the enormous metabolic potential of previously uncultured bacteria.

Five undescribed polyketide derivatives, pestaloketides A-E (1-5), along with eleven known analogues (6-16), were isolated from the sponge-derived fungus Pestalotiopsis sp. Their structures, including absolute configurations, were elucidated by analyses of NMR spectroscopic HRESIMS data and electronic circular dichroism (ECD) calculations. Compounds 5, 6, 9, and 14 exhibited weak cytotoxicities against four human cancer cell lines, with IC50 values ranging from 22.1 to 100 μM. Pestaloketide A (1) is an unusual polyketide, featuring a rare 5/10/5-fused ring system. Pestaloketides A (1) and B (2) exhibited moderately inhibited LPS-induced NO production activity, with IC50 values of 23.6 and 14.5 μM, respectively, without cytotoxicity observed. Preliminary bioactivity evaluations and molecular docking analysis indicated that pestaloketides A (1) and B (2) had the potential to be developed into anti-inflammatory activity drug leads.

Chemical examination of a marine sponge-associated Penicillium copticola fungus resulted in the isolation of ten undescribed eremophilanes, namely copteremophilanes A-J (1-10), along with two new glycosides, 5-glycopenostatin F (11) and 5-glucopenostatin I (12). Their structures were determined by extensive spectroscopic data, in association with ECD data and chemical conversions for configurational assignments. Analogs 1, 2, and 10 represent a group of uncommon skeletons of eremophilanes with an aromatic ring and a methyl migration from C-5 to C-9, and analogs 11 and 12 are characteristic of a PKS scaffold bearing a glucose unit. The incorporation of a chlorinated phenylacetic unit in 3-9 is rarely found in nature. Analog 7 showed neuroprotective effect, whereas 8 exhibited selective inhibition against human non-small cell lung cancer cells (A549). This study enriched the chemical diversity of eremophilanes and extended their bioactivities to neuroprotection.

A novel approach to producing high-purity fucoxanthinol (FXOH) was exploited as a sustainable method to maximize fucoxanthin (FX) utilization. Through fusing the genes of cholesterol esterase and SpyTag and then expressing them in Escherichia coli, the fusion chimera was self-assembled into insoluble active aggregates by SpyTag, which could be regarded as carrier-free immobilization. The immobilization yield of the active cholesterol esterase aggregates could reach 60%. They have expressed good activity retention at 92.48% and 60.13% after 3 and 12 cycles, respectively, which is an exciting finding. The conversion ratio of FX to FXOH is 95.02%, which is remarkably higher than those realized via the conventional chemical reduction method (55.86%) and the enzymatic hydrolysis method by free cholesterol esterases (84.51%). The purity of FXOH obtained by this method is as high as 98%, which is much higher than those obtained by other methods. Thus, a promising method for simultaneously purifying and immobilizing active cholesterol esterase aggregates is demonstrated in this study by SpyTag tailoring. In addition, this study provides an eco-friendly method for producing high-purity FXOH from FX in a highly efficient manner.

Oxidative stress-induced neuronal cell loss is considered to be the major mechanism underlying the pathogenesis of neurodegenerative diseases, which could be induced by a high concentration of glutamate. In this study, sargachromenol (SC) was isolated from a marine brown seaweed Sargassum horneri (S. horneri) and its neuroprotective effects against glutamate-induced oxidative stress in HT22 cells were investigated. An MTT assay was applied to assess the cytotoxicity of the SC, and the efficacies of SC were determined by flow cytometry, an analysis of ROS production, quantitative Real-Time PCR, and the Western blot assay. Our results showed that the pretreatment of SC reduced glutamate-induced apoptosis in HT22 cells via inhibiting the sub-G1 population, DNA fragmentation, and nuclear condensation, as well as up-regulating anti-apoptotic protein (Bcl-2) and down-regulating apoptotic proteins (Bax, p53, cleaved-PARP, caspase-3, caspase-9, and cytochrome c). Additionally, SC attenuated glutamate-induced oxidative stress by suppressing mitogen-activated protein kinases (MAPKs;ERK, JNK, and p38) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling (IκBα and NF-κB p65), while activating nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling (Nrf2; HO-1, and NQO-1). Our results suggest that SC could be used as a pharmacological candidate for the prevention and treatment of neurodegenerative diseases.

Neurodegenerative diseases are growing to become one of humanity's biggest health problems, given the number of individuals affected by them. They cause enough mortalities and severe economic impact to rival cancers and infections. With the current diversity of pathophysiological mechanisms involved in neurodegenerative diseases, on the one hand, and scarcity of efficient prevention and treatment strategies, on the other, all possible sources for novel drug discovery must be employed. Marine pharmacology represents a relatively uncharted territory to seek promising compounds, despite the enormous chemodiversity it offers. The current work discusses one vast marine region-the Northwestern or Russian Pacific-as the treasure chest for marine-based drug discovery targeting neurodegenerative diseases. We overview the natural products of neurological properties already discovered from its waters and survey the existing molecular and cellular targets for pharmacological modulation of the disease. We further provide a general assessment of the drug discovery potential of the Russian Pacific in case of its systematic development to tackle neurodegenerative diseases.

Halymenia durvillei is a red alga distributed along the coasts of Southeast Asian countries including Thailand. Previous studies have shown that an ethyl acetate fraction of H. durvillei (HDEA), containing major compounds including n-hexadecanoic acid, 2-butyl-5-hexyloctahydro-1H-indene, 3-(hydroxyacetyl) indole and indole-3-carboxylic acid, possesses high antioxidant and anti-lung cancer activities. The present study demonstrated that HDEA could protect mouse skin fibroblasts (L929) and human immortalized keratinocytes (HaCaT) against photoaging due to ultraviolet A and B (UVA and UVB) by reducing intracellular reactive oxygen species (ROS) and expressions of matrix metalloproteinases (MMP1 and MMP3), as well as increasing Nrf2 nuclear translocation, upregulations of mRNA transcripts of antioxidant enzymes, including superoxide dismutase (SOD), heme oxygenase (HMOX) and glutathione S-transferase pi1 (GSTP1), and procollagen synthesis. The results indicate that HDEA has the potential to protect skin cells from UV irradiation through the activation of the Nrf2 pathway, which leads to decreasing intracellular ROS and MMP production, along with the restoration of skin collagen.

The isolation and chemical characterization of phlorotannins has gained special attention in recent years due to their specific health-promoting benefits. Flow-cell ultrasound-assisted extraction (90 W/cm2 of sonication power, 2 min of retention time and 20 g solvent/g algae of liquid-solid ratio) was carried out by using double-distilled water (WE) and acetone:water mixture (AWE) as extraction solvents. The AWE showed a higher total polyphenols content (TPC), carbohydrates (CHOs) and antioxidant activities than WE. However, when the WE was purified by using Amberlite XAD16 column, the purified WE (PWE) showed similar a TPC, decreased CHOs and increased antioxidant activity compared to WE. The oxidation of the PWE extract was evaluated under natural, forced and severe oxidation condition for 120 h. Only severe oxidation conditions were able to significantly reduce TPC and antioxidant activities. PWE was dialyzed (20, 10, 3.5 and 2 kDa). The main bioactive fraction of phlorotannins was obtained from 10 to 20 kDa. CHOs were distributed in fractions below 20 kDa. MALDI-TOF analysis was performed for PWE, PD20 and PD2 extracts to analyze the degree of polymerization of phlorotannins, which ranged from 4 to 17 phloroglucinol units/molecule. Fragmentation patterns allowed the proximate identification of several phlorotannins in Ascophyllum nodosum extracts.

The in-depth study of fungal secondary metabolites (SMs) over the past few years has led to the discovery of a vast number of novel fungal SMs, some of which possess good biological activity. However, because of the limitations of the traditional natural product mining methods, the discovery of new SMs has become increasingly difficult. In recent years, with the rapid development of gene sequencing technology and bioinformatics, new breakthroughs have been made in the study of fungal SMs, and more fungal biosynthetic gene clusters of SMs have been discovered, which shows that the fungi still have a considerable potential to produce SMs. How to study these gene clusters to obtain a large number of unknown SMs has been a research hotspot. With the continuous breakthrough of molecular biology technology, gene manipulation has reached a mature stage. Methods such as gene knockout and heterologous expression techniques have been widely used in the study of fungal SM biosynthesis and have achieved good effects. In this review, the representative studies on the biosynthesis of fungal SMs by gene knockout and heterologous expression under the fungal genome mining in the last three years were summarized. The techniques and methods used in these studies were also briefly discussed. In addition, the prospect of synthetic biology in the future under this research background was proposed.

The anticancer properties of Laminaria japonica peptides (LJPs) have never been studied. Here, we extracted LJPs from fresh seaweed and explored their anti-liver cancer activity (in vivo and in vitro). LJPs were isolated/purified by HPLC-ESI-MS. HepG2 cell apoptosis and cell cycle were evaluated. MTT assays were used to examine the cytotoxicity of LJPs. Caspase activation of caspases 3 and 9, cleaved caspases 3 and 9, and cleaved PARP was examined by Western blotting. The PI3K/AKT pathway and the phosphorylation states of MAPKs (p38 and JNK) were examined. We found that the LJP-1 peptide had the most antiproliferative activity in H22 cells in vitro. LJP-1 blocked H22 cells in the G0/G1 phase, accompanied by inhibition of cyclin expression. LJP-1 induced apoptosis through caspase activation and regulation of the ASK1/MAPK pathway. Concurrent in vivo studies demonstrated that LJP-1 significantly inhibited tumor growth and induced tumor cell apoptosis/necrosis. In conclusion, LJPs, particularly LJP-1, exert strong inhibitory effects on liver cancer growth in vivo and in vitro. LJP-1 induces HCC cell apoptosis through the caspase-dependent pathway and G0/G1 arrest. LJP-1 induces caspase-dependent apoptosis, in part by inhibiting PI3K, MAPK signaling pathways, and cell cycle proteins. LJP-1 has the potential to be a novel candidate for human liver cancer therapeutics.

The sulfated echinoside A (EA) and holothurin A (HA) are two prominent saponins in sea cucumber with high hemolytic activity but also superior lipid-lowering activity. Deglycosylated derivatives EA2 and HA2 exhibit low hemolysis compared to EA and HA, but their efficacies on lipid metabolism regulation remains unknown. In this study, fatty acids-treated HepG2 cells and orotic acid-treated rats were used to investigate the lipid-lowering effects of sea cucumber saponin derivatives. Both the saponin and derivatives could effectively alleviate lipid accumulation in HepG2 model, especially EA and EA2. Moreover, though the lipid-lowering effect of EA2 was not equal with EA at the same dosage of 0.05% in diet, 0.15% dosage of EA2 significantly reduced hepatic steatosis rate, liver TC and TG contents by 76%, 41.5%, and 63.7%, respectively, compared to control and reversed liver histopathological features to normal degree according to H&E stained sections. Possible mechanisms mainly included enhancement of fatty acids β-oxidation and cholesterol catabolism through bile acids synthesis and excretion, suppression of lipogenesis and cholesterol uptake. It revealed that the efficacy of EA2 on lipid metabolism regulation was dose-dependent, and 0.15% dosage of EA2 possessed better efficacy with lower toxicity compared to 0.05% dosage of EA.

Despite its low prevalence, pancreatic cancer (PC) is one of the deadliest, typically characterised as silent in early stages and with a dramatically poor prognosis when in its advanced stages, commonly associated with a high degree of metastasis. Many efforts have been made in pursuing innovative therapeutical approaches, from the search for new cytotoxic drugs and other bioactive compounds, to the development of more targeted approaches, including improved drug delivery devices. Marine biotechnology has been contributing to this quest by providing new chemical leads and materials originating from different organisms. In this review, marine biodiscovery for PC is addressed, particularly regarding marine invertebrates (namely sponges, molluscs, and bryozoans), seaweeds, fungi, and bacteria. In addition, the development of biomaterials based on marine-originating compounds, particularly chitosan, fucoidan, and alginate, for the production of advanced cancer therapies, is also discussed. The key role that drug delivery can play in new cancer treatments is highlighted, as therapeutical outcomes need to be improved to give further hope to patients.

Tuberculosis has become a major health problem globally. This is worsened by the emergence of resistant strains of Mycobacterium tuberculosis showing ability to evade the effectiveness of the current antimycobacterial therapies. Therefore, the efforts carried out to explore new entities from many sources, including marine, are critical. This review summarizes several marine-derived macrolides that show promising activity against M. tuberculosis. We also provide information regarding the biosynthetic processes of marine macrolides, including the challenges that are usually experienced in this process. As most of the studies reporting the antimycobacterial activities of the listed marine macrolides are based on in vitro studies, the future direction should consider expanding the trials to in vivo and clinical trials. In addition, in silico studies should also be explored for a quick screening on marine macrolides with potent activities against mycobacterial infection. To sum up, macrolides derived from marine organisms might become therapeutical options for tackling antimycobacterial resistance of M. tuberculosis.

Thallusin, a highly biologically active, phytohormone-like and bacterial compound-inducing morphogenesis of the green tide-forming macroalga Ulva (Chlorophyta), was determined in bacteria and algae cultures. A sensitive and selective method was developed for quantification based on ultra-high-performance liquid chromatography coupled with electrospray ionization and a high-resolution mass spectrometer. Upon C18 solid phase extraction of the water samples, thallusin was derivatized with iodomethane to inhibit the formation of Fe-thallusin complexes interfering with the chromatographic separation. The concentration of thallusin was quantified during the relevant phases of the bacterial growth of Maribacter spp., ranging from 0.16 ± 0.01 amol cell-1 (at the peak of the exponential growth phase) to 0.86 ± 0.13 amol cell-1 (late stationary phase), indicating its accumulation in the growth medium. Finally, we directly determined the concentration of thallusin in algal culture to validate our approach for monitoring applications. Detection and quantification limits of 2.5 and 7.4 pmol L-1, respectively, were reached, which allow for quantifying ecologically relevant thallusin concentrations. Our approach will enable the surveying of thallusin in culture and in nature and will thus contribute to the chemical monitoring of aquaculture.

Up until now, the characterizations of GH50 agarases from Vibrio species have rarely been reported compared to GH16 agarases. In this study, a deep-sea strain, WPAGA4, was isolated and identified as Vibrio natriegens due to the maximum similarity of its 16S rRNA gene sequence, the values of its average nucleotide identity, and through digital DNA-DNA hybridization. Two circular chromosomes in V. natriegens WPAGA4 were assembled. A total of 4561 coding genes, 37 rRNA, 131 tRNA, and 59 other non-coding RNA genes were predicted in the genome of V. natriegens WPAGA4. An agarase gene belonging to the GH50 family was annotated in the genome sequence and expressed in E. coli cells. The optimum temperature and pH of the recombinant Aga3420 (rAga3420) were 40 °C and 7.0, respectively. Neoagarobiose (NA2) was the only product during the degradation process of agarose by rAga3420. rAga3420 had a favorable stability following incubation at 10-30 °C for 50 min. The Km, Vmax, and kcat values of rAga3420 were 2.8 mg/mL, 78.1 U/mg, and 376.9 s-1, respectively. rAga3420 displayed cold-adapted properties as 59.7% and 41.2% of the relative activity remained at 10 3 °C and 0 °C, respectively. This property ensured V. natriegens WPAGA4 could degrade and metabolize the agarose in cold deep-sea environments and enables rAga3420 to be an appropriate industrial enzyme for NA2 production, with industrial potential in medical and cosmetic fields.