Progressive aging harms bone tissue structure and function and, thus, requires effective therapies focusing on permanent tissue regeneration rather than partial cure, beginning with regenerative medicine. Due to advances in tissue engineering, stimulating osteogenesis with biomimetic nanoparticles to create a regenerative niche has gained attention for its efficacy and cost-effectiveness. In particular, hydroxyapatite (HAP, Ca₁₀(PO₄)₆(OH)₂) has gained significant interest in orthopedic applications as a major inorganic mineral of native bone. Recently, magnetic nanoparticles (MNPs) have also been noted for their multifunctional potential for hyperthermia, MRI contrast agents, drug delivery, and mechanosensitive receptor manipulation to induce cell differentiation, etc. Thus, the present study synthesizes HAP-decorated MNPs (MHAP NPs) via the wet chemical co-precipitation method. Synthesized MHAP NPs were evaluated against the preosteoblast MC3T3-E1 cells towards concentration-dependent cytotoxicity, proliferation, morphology staining, ROS generation, and osteogenic differentiation. The result evidenced that MHAP NPs concentration up to 10 µg/mL was non-toxic even with the time-dependent proliferation studies. As nanoparticle concentration increased, FACS apoptosis assay and ROS data showed a significant rise in apoptosis and ROS generation. The MC3T3-E1 cells cocultured with 5 µg/mL MHAP NPs showed significant osteogenic differentiation potential. Thus, MHAP NPs synthesized with simple wet chemistry could be employed in bone regenerative therapy. Full article

The title of this essay is as much a question as it is a statement. The discovery of the β-lactam antibiotics—including penicillins, cephalosporins, and carbapenems—as largely (if not exclusively) secondary metabolites of terrestrial fungi and bacteria, transformed modern medicine. The antibiotic β-lactams inactivate essential enzymes of bacterial cell-wall biosynthesis. Moreover, the ability of the β-lactams to function as enzyme inhibitors is of such great medical value, that inhibitors of the enzymes which degrade hydrolytically the β-lactams, the β-lactamases, have equal value. Given this privileged status for the β-lactam ring, it is therefore a disappointment that the exemplification of this ring in marine secondary metabolites is sparse. It may be that biologically active marine β-lactams are there, and simply have yet to be encountered. In this report, we posit a second explanation: that the value of the β-lactam to secure an ecological advantage in the marine environment might be compromised by its close structural similarity to the β-lactones of quorum sensing. The steric and reactivity similarities between the β-lactams and the β-lactones represent an outside-of-the-box opportunity for correlating new structures and new enzyme targets for the discovery of compelling biological activities. Full article

Culex pipiens mosquitoes are transmitters of many viruses and are associated with the transmission of many diseases, such as filariasis and avian malaria, that have a high rate of mortality. The current study draws attention to the larvicidal efficacy of three methanolic algal extracts, Cystoseira myrica, C. trinodis, and C. tamariscifolia, against the third larval instar of Cx. pipiens. The UPLC-ESI-MS analysis of three methanol fractions of algal samples led to the tentative characterization of twelve compounds with different percentages among the three samples belonging to phenolics and terpenoids. Probit analysis was used to calculate the lethal concentrations (LC₅₀ and LC₉₀). The highest level of toxicity was attained after treatment with C. myrica extract using a lethal concentration 50 (LC₅₀) of 105.06 ppm, followed by C. trinodis (135.08 ppm), and the lowest level of toxicity was achieved by C. tamariscifolia (138.71 ppm) after 24 h. The elevation of glutathione-S-transferase (GST) and reduction of acetylcholine esterase (AChE) enzymes confirm the larvicidal activity of the three algal extracts. When compared to untreated larvae, all evaluated extracts revealed a significant reduction in protein, lipid, and carbohydrate contents, verifying their larvicidal effectiveness. To further support the observed activity, an in silico study for the identified compounds was carried out on the two tested enzymes. Results showed that the identified compounds and the tested enzymes had excellent binding affinities for each other. Overall, the current work suggests that the three algal extractions are a prospective source for the development of innovative, environmentally friendly larvicides. Full article

Autophagy is widely implicated in pathophysiological processes such as tumors and metabolic and neurodegenerative disorders, making it an attractive target for drug discovery. Several chemical screening approaches have been developed to uncover autophagy-modulating compounds. However, the modulation capacity of marine compounds with significant pharmacological activities is largely unknown. We constructed an EGFP^KI-LC3B cell line using the CRISPR/Cas9 knock-in strategy in which green fluorescence indicated endogenous autophagy regulation. Using this cell line, we screened a compound library of approximately 500 marine natural products and analogues to investigate molecules that altered the EGFP fluorescence. We identified eight potential candidates that enhanced EGFP fluorescence, and HDYL-GQQ-495 was the leading one. Further validation with immunoblotting demonstrated that cleaved LC3 was increased in dose- and time-dependent manners, and the autophagy adaptor P62 showed oligomerization after HDYL-GQQ-495 treatment. We also demonstrated that HDYL-GQQ-495 treatment caused autophagy substrate aggregation, which indicated that HDYL-GQQ-495 serves as an autophagy inhibitor. Furthermore, HDYL-GQQ-495 induced Gasdermin E (GSDME) cleavage and promoted pyroptosis. Moreover, HDYL-GQQ-495 directly combined with P62 to induce P62 polymerization. In P62 knockout cells, the cleavage of LC3 or GSDME was blocked after HDYL-GQQ-495 treatment. The EGFP^KI-LC3B cell line was an effective tool for autophagy modulator screening. Using this tool, we found a novel marine-derived compound, HDYL-GQQ-495, targeting P62 to inhibit autophagy and promote pyroptosis. Full article

Depsipeptides, an important group of polypeptides containing residues of hydroxy acids and amino acids linked together by amide and ester bonds, have potential applications in agriculture and medicine. A growing body of evidence demonstrates that marine organisms are prolific sources of depsipeptides, such as marine cyanobacteria, sponges, mollusks, microorganisms and algae. However, these substances have not yet been comprehensively summarized. In order to enrich our knowledge about marine depsipeptides, their biological sources and structural features, as well as bioactivities, are highlighted in this review after an extensive literature search and data analysis. Full article

The determination of the protein’s intracellular localization is essential for understanding its biological function. Protein localization studies are mainly performed on primary and secondary vertebrate cell lines for which most protocols have been optimized. In spite of experimental difficulties, studies on invertebrate cells, including basal Metazoa, have greatly advanced. In recent years, the interest in studying human diseases from an evolutionary perspective has significantly increased. Sponges, placed at the base of the animal tree, are simple animals without true tissues and organs but with a complex genome containing many genes whose human homologs have been implicated in human diseases, including cancer. Therefore, sponges are an innovative model for elucidating the fundamental role of the proteins involved in cancer. In this study, we overexpressed human cancer-related proteins and their sponge homologs in human cancer cells, human fibroblasts, and sponge cells. We demonstrated that human and sponge MYC proteins localize in the nucleus, the RRAS2 in the plasma membrane, the membranes of the endolysosomal vesicles, and the DRG1 in the cell’s cytosol. Despite the very low transfection efficiency of sponge cells, we observed an identical localization of human proteins and their sponge homologs, indicating their similar cellular functions. Full article

Marine natural products (MNPs) play an important role in the discovery and development of new drugs. The Beibu Gulf of South China Sea harbors four representative marine ecosystems, including coral reefs, mangroves, seaweed beds, and coastal wetlands, which are rich in underexplored marine biological resources that produce a plethora of diversified MNPs. In our ongoing efforts to discover novel and biologically active MNPs from the Beibu Gulf, we provide a systematic overview of the sources, chemical structures, and bioactive properties of a total of 477 new MNPs derived from the Beibu Gulf, citing 133 references and covering the literature from the first report in November 2003 up to September 2022. These reviewed MNPs were structurally classified into polyketides (43%), terpenoids (40%), nitrogen-containing compounds (12%), and glucosides (5%), which mainly originated from microorganisms (52%) and macroorganisms (48%). Notably, they were predominantly found with cytotoxic, antibacterial, and anti-inflammatory activities. This review will shed light on these untapped Beibu Gulf-derived MNPs as promising lead compounds for the development of new drugs. Full article

Crustins are a kind of antimicrobial peptide (AMP) that exist in crustaceans. Some crustins do not have direct antimicrobial activity but exhibit in vivo defense functions against Vibrio. However, the underlying molecular mechanism is not clear. Here, the regulatory mechanism was partially revealed along with the characterization of the immune function of a type I crustin, LvCrustin I-2, from Litopenaeus vannamei. LvCrustin I-2 was mainly detected in hemocytes, intestines and gills and was apparently up-regulated after Vibrio parahaemolyticus infection. Although the recombinant LvCrustin I-2 protein possessed neither antibacterial activity nor agglutinating activity, the knockdown of LvCrustin I-2 accelerated the in vivo proliferation of V. parahaemolyticus. Microbiome analysis showed that the balance of intestinal microbiota was impaired after LvCrustin I-2 knockdown. Further transcriptome analysis showed that the intestinal epithelial barrier and immune function were impaired in shrimp after LvCrustin I-2 knockdown. After removing the intestinal bacteria via antibiotic treatment, the phenomenon of impaired intestinal epithelial barrier and immune function disappeared in shrimp after LvCrustin I-2 knockdown. This indicated that the impairment of the shrimp intestine after LvCrustin I-2 knockdown was caused by the dysbiosis of the intestinal microbiota. The present data suggest that crustins could resist pathogen infection through regulating the intestinal microbiota balance, which provides new insights into the functional mechanisms of antimicrobial peptides during pathogen infection. Full article

Dinophysis acuminata and D. acuta, which follows it seasonally, are the main producers of lipophilic toxins in temperate coastal waters, including Southern Chile. Strains of the two species differ in their toxin profiles and impacts on shellfish resources. D. acuta is considered the major cause of diarrhetic shellfish poisoning (DSP) outbreaks in Southern Chile, but there is uncertainty about the toxicity of D. acuminata, and little information on microscale oceanographic conditions promoting their blooms. During the austral summer of 2020, intensive sampling was carried out in two northern Patagonian fjords, Puyuhuapi (PUY) and Pitipalena (PIT), sharing D. acuminata dominance and D. acuta near detection levels. Dinophysistoxin 1 (DTX 1) and pectenotoxin 2 (PTX 2) were present in all net tow samples but OA was not detected. Although differing in hydrodynamics and sampling dates, D. acuminata shared behavioural traits in the two fjords: cell maxima (>10³ cells L⁻¹) in the interface (S ~ 21) between the estuarine freshwater (EFW)) and saline water (ESW) layers; and phased-cell division (µ = 0.3–0.4 d⁻¹) peaking after dawn, and abundance of ciliate prey. Niche analysis (Outlying Mean Index, OMI) of D. acuta with a high marginality and much lower tolerance than D. acuminata indicated an unfavourable physical environment for D. acuta (bloom failure). Comparison of toxin profiles and Dinophysis niches in three contrasting years in PUY—2020 (D. acuminata bloom), 2018 (exceptional bloom of D. acuta), and 2019 (bloom co-occurrence of the two species)—shed light on the vertical gradients which promote each species. The presence of FW (S < 11) and thermal inversion may be used to provide short-term forecasts of no risk of D. acuta blooms and OA occurrence, but D. acuminata associated with DTX 1 pose a risk of DSP events in North Patagonian fjords. Full article

Arthropods, the largest animal phylum, including insects, spiders and crustaceans, are characterized by their bodies being covered primarily in chitin. Besides being a source of this biopolymer, crustaceans have also attracted attention from biotechnology given their cuticles’ remarkable and diverse mechanical properties. The goose barnacle, Pollicipes pollicipes, is a sessile crustacean characterized by their body parts covered with calcified plates and a peduncle attached to a substrate covered with a cuticle. In this work, the composition and structure of these plates and cuticle were characterized. The morphology of the tergum plate revealed a compact homogeneous structure of calcium carbonate, a typical composition among marine invertebrate hard structures. The cuticle consisted of an outer zone covered with scales and an inner homogenous zone, predominantly organic, composed of successive layers parallel to the surface. The scales are similar to the tergum plate and are arranged in parallel and oriented semi-vertically. Structural and biochemical characterization confirmed a bulk composition of ɑ-chitin and suggested the presence of elastin-based proteins and collagen. The mechanical properties of the cuticle showed that the stiffness values are within the range of values described in elastomers and soft crustacean cuticles resulting from molting. The removal of calcified components exposed round holes, detailed the structure of the lamina, and changed the protein properties, increasing the rigidity of the material. This flexible cuticle, predominantly inorganic, can provide bioinspiration for developing biocompatible and mechanically suitable biomaterials for diverse applications, including in tissue engineering approaches. Full article

Aquatic-based collagens have attracted much interest due to their great potential application for biomedical sectors, including the tissue engineering sector, as a major component of the extracellular matrix in humans. Their physical and biochemical characteristics offer advantages over mammalian-based collagen; for example, they have excellent biocompatibility and biodegradability, are easy to extract, and pose a relatively low immunological risk to mammalian products. The utilization of aquatic-based collagen also has fewer religious restrictions and lower production costs. Aquatic-based collagen also creates high-added value and good environmental sustainability by aquatic waste utilization. Thus, this study aims to overview aquatic collagen’s characteristics, extraction, and fabrication. It also highlights its potential application for tissue engineering and the regeneration of bone, cartilage, dental, skin, and vascular tissue. Moreover, this review highlights the recent research in aquatic collagen, future prospects, and challenges for it as an alternative biomaterial for tissue engineering and regenerative medicines. Full article

The content of bioactive compounds in four brown and one red algae from the Adriatic Sea (Dictyota dichotoma, Gongolaria barbata, Ericaria amentacea, Sargassum hornschuchii and Ellisolandia elongata) is explored. The efficiency of two different extraction methods viz. ultrasound-assisted extraction (UAE) and matrix solid-phase dispersion (MSPD) to obtain the extracts rich in phenolic compounds was compared. The effect of the extraction solvent to modulate the phenolic profile was assessed. In general, the mixture ethanol/water in an isovolumetric proportion showed the best results. The total phenolic content (TPC) and antioxidant activity (AA), as well as the individual polyphenolic profile, were evaluated for five target algae. TPC values ranged between 0.2 mg GAE/g (for E. elongata) and 38 mg GAE/g (for S. hornschuchii). Regarding the quantification of individual polyphenols by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, the presence of a high number of hydroxybenzoic acid derivatives (mainly of 3- and 4-hydroxybenzoic acids) in all species was noted. In G. barbata their concentrations reached up to 500 mg/kg. IC₅₀ values (ABTS assay) ranged between 44 mg/L (for S. hornschuchii) and 11,040 mg/L (for E. elongata). This work contributes to the in-depth characterization of these little-explored algae, showing their potential as a natural source of phenolic compounds. Full article

Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could be regarded as the most promising candidate—it demonstrated over 85% growth inhibition against Botrytis cinerea, Gibberella zeae, and Colletotrichum lagenarium, as well as a broad antifungal spectrum in primary screening at the concentration of 50 μg/mL. The SAR study revealed that non-substituent or alkyl substituent at the 2-position of oxazole ring were favorable for antifungal activity, while aryl and monosubstituted aryl were detrimental to activity. Molecular docking models indicated that 3a formed hydrogen bonds and hydrophobic interactions with Leucyl-tRNA Synthetase, offering a perspective for the possible mechanism of action for antifungal activity of the target compounds. Full article

Urban particulate matter (UPM) causes skin aging and inflammatory reactions by influencing skin cells through the aryl hydrocarbon receptor (AhR) signaling pathway. Porphyra yezoensis (also known as Pyropia yezoensis), a red alga belonging to the Bangiaceae family, is an edible red seaweed. Here, we examined the anti-pollutant effect of P. yezoensis water extract. While UPM treatment induced xenobiotic response element (XRE) promoter luciferase activity, P. yezoensis water extract reduced UPM-induced XRE activity. Next, we isolated an active compound from P. yezoensis and identified it as porphyra 334. Similar to the P. yezoensis water extract, porphyra 334 attenuated UPM-induced XRE activity. Moreover, although UPM augmented AhR nuclear translocation, which led to an increase in cytochrome P450 1A1 (CYP1A1) mRNA levels, these effects were reduced by porphyra 334. Moreover, UPM induced the production of reactive oxygen species (ROS) and reduced cell proliferation. These effects were attenuated in response to porphyra 334 treatment. Furthermore, our results revealed that the increased ROS levels induced by UPM treatment induced transient receptor potential vanilloid 1 (TRPV1) activity, which is related to skin aging and inflammatory responses. However, porphyra 334 treatment reduced this reaction by inhibiting ROS production induced by CYP1A1 activation. This indicates that porphyra 334, an active compound of P. yezoensis, attenuates UP-induced cell damage by inhibiting AhR-induced ROS production, which results in a reduction in TRPV1 activation, leading to cell proliferation. This also suggests that porphyra 334 could protect the epidermis from harmful pollutants. Full article

Antarctic krill (Euphausia superba) of the Euphausiidae family comprise one of the largest biomasses in the world and play a key role in the Antarctic marine ecosystem. However, the study of E. superba-derived microbes and their secondary metabolites has been limited. Chemical investigation of the secondary metabolites of the actinomycetes Nocardiopsis sp. LX-1 (in the family of Nocardiopsaceae), isolated from E. superba, combined with molecular networking, led to the identification of 16 compounds a–p (purple nodes in the molecular network) and the isolation of one new pyrroline, nocarpyrroline A (1), along with 11 known compounds 2–12. The structure of the new compound 1 was elucidated by extensive spectroscopic investigation. Compound 2 exhibited broad-spectrum antibacterial activities against A. hydrophila, D. chrysanthemi, C. terrigena, X. citri pv. malvacearum and antifungal activity against C. albicans in a conventional broth dilution assay. The positive control was ciprofloxacin with the MIC values of <0.024 µM, 0.39 µM, 0.39 µM, 0.39 µM, and 0.20 µM, respectively. Compound 1 and compounds 7, 10, and 11 displayed antifungal activities against F. fujikuroi and D. citri, respectively, in modified agar diffusion test. Prochloraz was used as positive control and showed the inhibition zone radius of 17 mm and 15 mm against F. fujikuroi and D. citri, respectively. All the annotated compounds a–p by molecular networking were first discovered from the genus Nocardiopsis. Nocarpyrroline A (1) features an unprecedented 4,5-dihydro-pyrrole-2-carbonitrile substructure, and it is the first pyrroline isolated from the genus Nocardiopsis. This study further demonstrated the guiding significance of molecular networking in the research of microbial secondary metabolites. Full article