Marine Drugs

Deep-sea mussels of the genus Bathymodiolus exhibit adaptability to nutrient-poor deep-sea environments by establishing nutritional intracellular symbiosis with chemosynthetic bacteria harbored within the gill epithelial cells. However, this poses a conflict for the innate immune system of the host, which must balance the tolerance of beneficial symbiotic bacteria with the need to eliminate exogenous microbes. This review synthesizes existing knowledge and recent findings on Bathymodiolus japonicus to outline the cellular and molecular mechanisms governing this symbiotic relationship. In the host immune system, hemocytes are responsible for systemic defense, whereas gill cells are involved in local symbiotic acceptance. Central to the establishment of symbiosis is the host’s phagocytic system, which non-selectively engulfs bacteria but selectively retains symbionts. We highlight a series of cellular events in gill cells involving the engulfment, selection, retention and/or digestion of symbionts, and the regulatory mechanism of phagocytosis through mechanistic target of rapamycin complex 1, which connects bacterial nutrient supply with host immune and metabolic responses. This integrated model of symbiosis regulation, which links immunity, metabolism, and symbiosis, provides a fundamental framework for understanding how hosts establish and maintain a stable coexistence with microbes, offering a new perspective on symbiotic strategies in diverse organisms.

Marine diatoms are an important group of phytoplankton that can shape marine ecosystems and global carbon cycling. When stressed, either physiologically or by grazing, diatoms release oxidized, lipid-derived signals known as oxylipins. Diatom-derived oxylipins are proposed to serve as defense and signaling chemicals that affect multiple components of marine ecosystems. Therefore, to elucidate the diversity of diatom-derived oxylipins produced during stress, we profiled the spectrum of dissolved lipids of five diatom species in culture under silicon limitation and across growth phases using ultra-high performance liquid chromatography coupled with high-resolution accurate mass spectrometry. In this study, we present evidence that physiological changes associated with Si-limitation elicit the extracellular release of linear oxygenated fatty acids (LOFAs) across five diatom species. For diatoms like Skeletonema japonicum and Pseudo-nitzschia multiseries, silicon limitation induced a distinct lipidomic signature driven by oxylipins known to be allelopathic. While their lipoxygenases were found to be different, S. japonicum and P. multiseries had the most similar dissolved lipidomes, suggesting alternative controls on oxylipin biosynthesis. Consequently, elevated oxylipin concentrations with silicon stress, estimated up to 5.91 µM, pose implications for diatoms at sea, potentially affecting ecosystems and biogeochemistry.

Galectin-3 (Gal-3) is a histologic marker of pancreatic cancer and a potential therapeutic target. This study aimed to characterize a novel sulfated agarose-derived oligosaccharide (DP9) from marine algae, Gracilaria lemaneiformis, evaluate its Gal-3 inhibitory activity, and investigate its anti-pancreatic cancer mechanisms. Through controlled acid hydrolysis, a series of odd-numbered oligosaccharides (DP3-11) were obtained, in which DP9 showed the strongest Gal-3 inhibition in hemagglutination assays. Structural analysis confirmed DP9’s unique composition including an alternating β (1→4)-D-galactose and α (1→3)-3,6-anhydro-L-galactose backbone, featuring partial 6-O-methylation on β-D-galactose and 6-O-sulfation on 3,6-anhydro-α-L-galactose residues. Molecular docking revealed DP9’s binding to Gal-3’s carbohydrate recognition domain through key hydrogen bonds (His158, Arg162, Lys176, Asn179 and Arg186) and hydrophobic interactions (Pro117, Asn119, Trp181 and Gly235), with the sulfate group enhancing binding affinity. In vitro studies demonstrated DP9’s selective anti-pancreatic cancer activity against BxPC-3 cells, including inhibition of cell proliferation; S-phase cell cycle arrest; induction of apoptosis; and suppression of migration and invasion. Mechanistically, DP9 attenuated the Gal-3/EGFR/AKT/FOXO3 signaling pathway while showing minimal cytotoxicity to normal cells. This study first demonstrated that agarose-derived odd-numbered oligosaccharides (DP9) can serve as effective Gal-3 inhibitors, which proved its potential as a marine oligosaccharide-based therapeutic agent for pancreatic cancer.