An Update of Lectins from Marine Organisms: Characterization,Extraction Methodology,and Potential Biofunctional Applications

Lectins are a unique group of nonimmune carbohydrate-binding proteins or glycoproteins that exhibit specific and reversible carbohydrate-binding activity in a non-catalytic manner. Lectins have diverse sources and are classified according to their origins, such as plant lectins, animal lectins, and fish lectins. Marine organisms including fish, crustaceans, and mollusks produce a myriad of lectins, including rhamnose binding lectins (RBL), fucose-binding lectins (FTL), mannose-binding lectin, galectins, galactose binding lectins, and C-type lectins. The widely used method of extracting lectins from marine samples is a simple two-step process employing a polar salt solution and purification by column chromatography. Lectins exert several immunomodulatory functions, including pathogen recognition, inflammatory reactions, participating in various hemocyte functions (e.g., agglutination), phagocytic reactions, among others. Lectins can also control cell proliferation, protein folding, RNA splicing, and trafficking of molecules. Due to their reported biological and pharmaceutical activities, lectins have attracted the attention of scientists and industries (i.e., food, biomedical, and pharmaceutical industries). Therefore, this review aims to update current information on lectins from marine organisms, their characterization, extraction, and biofunctionalities.     

Exploring Marine as a Rich Source of Bioactive Peptides: Challenges and Opportunities from Marine Pharmacology

This review highlights the underexplored potential and promises of marine bioactive peptides (MBPs) with unique structural, physicochemical, and biological activities to fight against the current and future human pathologies. A particular focus is given to the marine environment as a significant source to obtain or extract high-value MBPs from touched/untouched sources. For instance, marine microorganisms, including microalgae, bacteria, fungi, and marine polysaccharides, are considered prolific sources of amino acids at large, and peptides/polypeptides in particular, with fundamental structural sequence and functional entities of a carboxyl group, amine, hydrogen, and a variety of R groups. Thus, MBPs with tunable features, both structural and functional entities, along with bioactive traits of clinical and therapeutic value, are of ultimate interest to reinforce biomedical settings in the 21st century. On the other front, as the largest biome globally, the marine biome is the so-called “epitome of untouched or underexploited natural resources” and a considerable source with significant potentialities. Therefore, considering their biological and biomedical importance, researchers around the globe are redirecting and/or regaining their interests in valorizing the marine biome-based MBPs. This review focuses on the widespread bioactivities of MBPs, FDA-approved MBPs in the market, sustainable development goals (SDGs), and legislation to valorize marine biome to underlying the impact role of bioactive elements with the related pathways. Finally, a detailed overview of current challenges, conclusions, and future perspectives is also given to satisfy the stimulating demands of the pharmaceutical sector of the modern world.     

Efficient Purification of R-phycoerythrin from Marine Algae (Porphyra yezoensis) Based on a Deep Eutectic Solvents Aqueous Two-Phase System

R-phycoerythrin (R-PE), a marine bioactive protein, is abundant in Porphyra yezoensis with high protein content. In this study, R-PE was purified using a deep eutectic solvents aqueous two-phase system (DES-ATPS), combined with ammonium sulphate precipitation, and characterized by certain techniques. Firstly, choline chloride-urea (ChCl-U) was selected as the suitable DES to form ATPS for R-PE extraction. Then, single-factor experiments were conducted: the purity (A₅₆₅/A₂₈₀) of R-PE was 3.825, and the yield was 69.99% (w/w) under optimal conditions (adding 0.040 mg R-PE to ChCl-U (0.35 g)/K₂HPO₄ (0.8 g/mL, 0.5 mL) and extracting for 20 min). The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results revealed that the purified R-PE contained three main bands. One band was presented after purification in native-PAGE. The UV-vis spectra showed characteristic absorption peaks at 495, 540, and 565 nm. R-PE displayed an emission wavelength at 570 nm when excited at 495 nm. All spectra results illustrated that the structure of R-PE remained unchanged throughout the process, proving the effectiveness of this method. Transmission electron microscope (TEM) showed that aggregation and surrounding phenomena were the driving forces for R-PE extraction. This study could provide a green and simple purification method of R-PE in drug development.     

Overview on Biological Activities and Molecular Characteristics of Sulfated Polysaccharides from Marine Green Algae in Recent Years

Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their numerous health beneficial effects. Green seaweeds are known to synthesize large quantities of SPs and are well established sources of these particularly interesting molecules such as ulvans from Ulva and Enteromorpha, sulfated rhamnans from Monostroma, sulfated arabinogalactans from Codium, sulfated galacotans from Caulerpa, and some special sulfated mannans from different species. These SPs exhibit many beneficial biological activities such as anticoagulant, antiviral, antioxidative, antitumor, immunomodulating, antihyperlipidemic and antihepatotoxic activities. Therefore, marine algae derived SPs have great potential for further development as healthy food and medical products. The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits.     

The Effects of Marine Algal Polyphenols,Phlorotannins, on Skeletal Muscle Growth in C2C12 Muscle Cells via Smad and IGF-1 Signaling Pathways

Skeletal muscle is an important tissue in energy metabolism and athletic performance. The use of effective synthetic supplements and drugs to promote muscle growth is limited by various side effects. Moreover, their use is prohibited by anti-doping agencies; hence, natural alternatives are needed. Therefore, we evaluated the muscle growth effect of substances that can act like synthetic supplements from edible marine algae. First, we isolated six marine algal polyphenols belonging to the phlorotannin class, namely dieckol (DK), 2,7″-phloroglucinol-6,6′-bieckol (PHB), phlorofucofuroeckol A (PFFA), 6,6′-bieckol (6,6-BK), pyrogallol-phloroglucinol-6,6′-bieckol (PPB), and phloroglucinol (PG) from an edible brown alga, Ecklonia cava and evaluated their effects on C2C12 myoblasts proliferation and differentiation. Of the six phlorotannin isolates evaluated, DK and PHB induced the highest degree of C2C12 myoblast proliferation. In addition, DK and PHB regulates myogenesis by down-regulating the Smad signaling, a negative regulator, and up-regulating the insulin-like growth factor-1 (IGF-1) signaling, a positive regulator. Interestingly, DK and PHB bind strongly to myostatin, which is an inhibitor of myoblast proliferation, while also binding to IGF-1 receptors. Moreover, they bind to IGF-1 receptor. These results suggest that DK and PHB are potential natural muscle building supplements and could be a safer alternative to synthetic drugs.     

Bacterial Exopolysaccharides from Extreme Marine Habitats: Production,Characterization and Biological Activities

Many marine bacteria produce exopolysaccharides (EPS) as a strategy for growth, adhering to solid surfaces, and to survive adverse conditions. There is growing interest in isolating new EPS producing bacteria from marine environments, particularly from extreme marine environments such as deep-sea hydrothermal vents characterized by high pressure and temperature and heavy metal presence. Marine EPS-producing microorganisms have been also isolated from several extreme niches such as the cold marine environments typically of Arctic and Antarctic sea ice, characterized by low temperature and low nutrient concentration, and the hypersaline marine environment found in a wide variety of aquatic and terrestrial ecosystems such as salt lakes and salterns. Most of their EPSs are heteropolysaccharides containing three or four different monosaccharides arranged in groups of 10 or less to form the repeating units. These polymers are often linear with an average molecular weight ranging from 1 × 10⁵ to 3 × 10⁵ Da. Some EPS are neutral macromolecules, but the majority of them are polyanionic for the presence of uronic acids or ketal-linked pyruvate or inorganic residues such as phosphate or sulfate. EPSs, forming a layer surrounding the cell, provide an effective protection against high or low temperature and salinity, or against possible predators. By examining their structure and chemical-physical characteristics it is possible to gain insight into their commercial application, and they are employed in several industries. Indeed EPSs produced by microorganisms from extreme habitats show biotechnological promise ranging from pharmaceutical industries, for their immunomodulatory and antiviral effects, bone regeneration and cicatrizing capacity, to food-processing industries for their peculiar gelling and thickening properties. Moreover, some EPSs are employed as biosurfactants and in detoxification mechanisms of petrochemical oil-polluted areas. The aim of this paper is to give an overview of current knowledge on EPSs produced by marine bacteria including symbiotic marine EPS-producing bacteria isolated from some marine annelid worms that live in extreme niches.     

Marine Sponge Derived Natural Products between 2001 and 2010: Trends and Opportunities for Discovery of Bioactives

Marine sponges belonging to the phylum Porifera (Metazoa), evolutionarily the oldest animals are the single best source of marine natural products. The present review presents a comprehensive overview of the source, taxonomy, country of origin or geographical position, chemical class, and biological activity of sponge-derived new natural products discovered between 2001 and 2010. The data has been analyzed with a view to gaining an outlook on the future trends and opportunities in the search for new compounds and their sources from marine sponges.     

Supercritical Fluid Extraction of Fucoxanthin from the Diatom Phaeodactylum tricornutum and Biogas Production through Anaerobic Digestion

Phaeodactylum tricornutum is the marine diatom best known for high-value compounds that are useful in aquaculture and food area. In this study, fucoxanthin was first extracted from the diatom using supercritical fluid extraction (SFE) and then using the extracted diatom-like substrate to produce bioenergy through anaerobic digestion (AD) processes. Factors such as temperature (30 °C and 50 °C), pressure (20, 30, and 40 MPa), and ethanol (co-solvent concentration from 10% to 50% v/v) were optimized for improving the yield, purity, and recovery of fucoxanthin extracted using SFE. The highest yield (24.41% w/w) was obtained at 30 MPa, 30 °C, and 30% ethanol but the highest fucoxanthin purity and recovery (85.03mg/g extract and 66.60% w/w, respectively) were obtained at 30 MPa, 30 °C, and 40%ethanol. Furthermore, ethanol as a factor had the most significant effect on the overall process of SFE. Subsequently, P.tricornutum biomass and SFE-extracted diatom were used as substrates for biogas production through AD. The effect of fucoxanthin was studied on the yield of AD, which resulted in 77.15 ± 3.85 LSTP CH₄/kg volatile solids (VS) and 56.66 ± 1.90 LSTP CH₄/kg VS for the whole diatom and the extracted P.tricornutum, respectively. Therefore, P.tricornutuman can be considered a potential source of fucoxanthin and methane and both productions will contribute to the sustainability of the algae-biorefinery processes.     

南京市六合区水稻生产现状与发展对策

阐述了六合区水稻生产现状及问题,分析了影响水稻生产的制约因素,提出了水稻生产要保持稳定发展,必须确立水稻当家品种,规范种子经营秩序;重视基层农技服务工作,促进新品种、新技术的推广应用;加强主推技术的配套完善,推进现代稻作技术的规范化;加强防灾减灾,推进水稻安全生产;推广"水稻+N"高效栽培模式,加大稻、麦(油)两熟耕作制度创新等对策。     

Therapeutic Potential of Marine Bioactive Peptides against Human Immunodeficiency Virus: Recent Evidence,Challenges, and Future Trends

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

Marine polysaccharides: a source of bioactive molecules for cell therapy and tissue engineering

The therapeutic potential of natural bioactive compounds such as polysaccharides, especially glycosaminoglycans, is now well documented, and this activity combined with natural biodiversity will allow the development of a new generation of therapeutics. Advances in our understanding of the biosynthesis, structure and function of complex glycans from mammalian origin have shown the crucial role of this class of molecules to modulate disease processes and the importance of a deeper knowledge of structure-activity relationships. Marine environment offers a tremendous biodiversity and original polysaccharides have been discovered presenting a great chemical diversity that is largely species specific. The study of the biological properties of the polysaccharides from marine eukaryotes and marine prokaryotes revealed that the polysaccharides from the marine environment could provide a valid alternative to traditional polysaccharides such as glycosaminoglycans. Marine polysaccharides present a real potential for natural product drug discovery and for the delivery of new marine derived products for therapeutic applications.     

Marine Microbial Fibrinolytic Enzymes: An Overview of Source,Production, Biochemical Properties and Thrombolytic Activity

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

Quorum Sensing Inhibition by Asparagopsis taxiformis,a Marine Macro Alga: Separation of the Compound that Interrupts Bacterial Communication

The majority of the marine algal species, though completing their life cycle in seawater, are rarely susceptible to fouling, making them an important source of quorum sensing (QS) inhibitory substances. The separation and characterization of QS inhibitors are crucial for any potential application. Thirty marine macroalgae were tested for QS inhibition activity by using Chromobacterium violaceum CV026 as the reporter strain, and among them, Asparagopsis taxiformis showed antibacterial, as well as antiquorum, sensing activities. Cinnamaldehyde (75 mM) and methanol were used as positive and negative controls, respectively. The antiquorum sensing activity of A. taxiformis was further confirmed using the sensor strain, Serratia liquefaciens MG44, having green fluorescent protein (gfp). Methanolic extract of the alga was fractionated by solid phase extraction (SPE), and each fraction was tested for QS inhibition. Two types of activities were observed—zone of clearance (antibacterial activity) and zone of inhibition with or without finger-like projections (QS inhibition). Out of five SPE cartridges, Bond Elut PH showed clear separation of these two fractions. The Ion Cyclotron Resonance Fourier Transformation Mass Spectrometer (ICR-FT/MS) analysis of the fractions further supported the bioassay results. The presence of strong QS inhibitory compound in A. taxiformis indicates its potential use in antifouling preparations.     

Bioprospecting from Marine Sediments of New Brunswick,Canada: Exploring the Relationship between Total Bacterial Diversity and Actinobacteria Diversity

Actinomycetes are an important resource for the discovery of natural products with therapeutic properties. Bioprospecting for actinomycetes typically proceeds without a priori knowledge of the bacterial diversity present in sampled habitats. In this study, we endeavored to determine if overall bacterial diversity in marine sediments, as determined by 16S rDNA amplicon pyrosequencing, could be correlated with culturable actinomycete diversity, and thus serve as a powerful tool in guiding future bioprospecting efforts. Overall bacterial diversity was investigated in eight marine sediments from four sites in New Brunswick, Canada, resulting in over 44,000 high quality sequences (x = 5610 per sample). Analysis revealed all sites exhibited significant diversity (H’ = 5.4 to 6.7). Furthermore, statistical analysis of species level bacterial communities (D = 0.03) indicated community composition varied according to site and was strongly influenced by sediment physiochemical composition. In contrast, cultured actinomycetes (n = 466, 98.3% Streptomyces) were ubiquitously distributed among all sites and distribution was not influenced by sediment composition, suggesting that the biogeography of culturable actinomycetes does not correlate with overall bacterial diversity in the samples examined. These actinomycetes provide a resource for future secondary metabolite discovery, as exemplified by the antimicrobial activity observed from preliminary investigation.     

Marine Biotechnology: Challenges and Development Market Trends for the Enhancement of Biotic Resources in Industrial Pharmaceutical and Food Applications. A Statistical Analysis of Scientific Literature and Business Models

Biotechnology is an essential tool for the sustainable exploitation of marine resources, although the full development of their potential is complicated by a series of cognitive and technological limitations. Thanks to an innovative systematic approach that combines the meta-analysis of 620 articles produced worldwide with 29 high TRL (Technology Readiness Level) European funded projects, the study provides an assessment of the growth prospects of blue biotechnologies, with a focus on pharmaceutical and food applications, and the most promising technologies to overcome the main challenges in the commercialization of marine products. The results show a positive development trend, with publications more than doubled from 2010 (36) to 2019 (70). Biochemical and molecular characterization, with 150 studies, is the most widely used technology. However, the emerging technologies in basic research are omics technologies, pharmacological analysis and bioinformatics, which have doubled the number of publications in the last five years. On the other hand, technologies for optimizing the conditions of cultivation, harvesting and extraction are central to most business models with immediate commercial exploitation (65% of high-TRL selected projects), especially in food and nutraceutical applications. This research offers a starting point for future research to overcome all those obstacles that restrict the marketing of products derived from organisms.     

Ethanol Extraction of Polar Lipids from Nannochloropsis oceanica for Food,Feed, and Biotechnology Applications Evaluated Using Lipidomic Approaches

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

Evaluation of Ultrasound,Microwave, Ultrasound–Microwave,Hydrothermal and High Pressure Assisted Extraction Technologies for the Recovery of Phytochemicals and Antioxidants from Brown Macroalgae

This study aims to explore novel extraction technologies (ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), ultrasound–microwave-assisted extraction (UMAE), hydrothermal-assisted extraction (HAE) and high-pressure-assisted extraction (HPAE)) and extraction time post-treatment (0 and 24 h) for the recovery of phytochemicals and associated antioxidant properties from Fucus vesiculosus and Pelvetia canaliculata. When using fixed extraction conditions (solvent: 50% ethanol; extraction time: 10 min; algae/solvent ratio: 1/10) for all the novel technologies, UAE generated extracts with the highest phytochemical contents from both macroalgae. The highest yields of compounds extracted from F. vesiculosus using UAE were: total phenolic content (445.0 ± 4.6 mg gallic acid equivalents/g), total phlorotannin content (362.9 ± 3.7 mg phloroglucinol equivalents/g), total flavonoid content (286.3 ± 7.8 mg quercetin equivalents/g) and total tannin content (189.1 ± 4.4 mg catechin equivalents/g). In the case of the antioxidant activities, the highest DPPH activities were achieved by UAE and UMAE from both macroalgae, while no clear pattern was recorded in the case of FRAP activities. The highest DPPH scavenging activities (112.5 ± 0.7 mg trolox equivalents/g) and FRAP activities (284.8 ± 2.2 mg trolox equivalents/g) were achieved from F. vesiculosus. Following the extraction treatment, an additional storage post-extraction (24 h) did not improve the yields of phytochemicals or antioxidant properties of the extracts.     

The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore,ADMET, Molecular Docking and Molecular Dynamics Study

Background: CDK4/6 (Cyclin-dependent kinases 4/6) are the key promoters of cell cycle transition from G1 phase to S phase. Thus, selective inhibition of CDK4/6 is a promising cancer treatment. Methods: A total of 52,765 marine natural products were screened for CDK4/6. To screen out better natural compounds, pharmacophore models were first generated, then the absorption, distribution, metabolism, elimination, and toxicity (ADMET) were tested, followed by molecular docking. Finally, molecular dynamics simulation was carried out to verify the binding characteristics of the selected compounds. Results: Eighty-seven marine small molecules were screened based on the pharmacophore model. Then, compounds 41369 and 50843 were selected according to the ADMET and molecular docking score for further kinetic simulation evaluation. Finally, through molecular dynamics analysis, it was confirmed that compound 50843 maintained a stable conformation with the target protein, so it has the opportunity to become an inhibitor of CDK4/6. Conclusion: Through structure-based pharmacophore modeling, ADMET, the molecular docking method and molecular dynamics (MD) simulation, marine natural compound 50843 was proposed as a promising marine inhibitor of CDK4/6.     

Production,Characterization and Biocompatibility of Marine Collagen Matrices from an Alternative and Sustainable Source: The Sea Urchin Paracentrotus lividus

Collagen has become a key-molecule in cell culture studies and in the tissue engineering field. Industrially, the principal sources of collagen are calf skin and bones which, however, could be associated to risks of serious disease transmission. In fact, collagen derived from alternative and riskless sources is required, and marine organisms are among the safest and recently exploited ones. Sea urchins possess a circular area of soft tissue surrounding the mouth, the peristomial membrane (PM), mainly composed by mammalian-like collagen. The PM of the edible sea urchin Paracentrotus lividus therefore represents a potential unexploited collagen source, easily obtainable as a food industry waste product. Our results demonstrate that it is possible to extract native collagen fibrils from the PM and produce suitable substrates for in vitro system. The obtained matrices appear as a homogeneous fibrillar network (mean fibril diameter 30–400 nm and mesh < 2 μm) and display remarkable mechanical properties in term of stiffness (146 ± 48 MPa) and viscosity (60.98 ± 52.07 GPa·s). In vitro tests with horse pbMSC show a good biocompatibility in terms of overall cell growth. The obtained results indicate that the sea urchin P. lividus can be a valuable low-cost collagen source for mechanically resistant biomedical devices.