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Biopeptides from Sipunculus nudus were reported with good ACE inhibitory activity, and the tripeptide SRP was one with the highest ACE inhibition rate. However, the disadvantage of short half-life limited the development of peptide drugs. Moreover, the distinct mechanism of the peptide inhibiting ACE remained unknown. Thus, in this study, a sustained release formulation of SRP-PLGA-MS was designed and prepared. Its long-lasting antihypertensive effect as well as improvement of vascular pathomorphology was verified in spontaneously hypertensive rat (SHR). In addition, the anti-oxidant activity of SRP in human umbilical vein endothelial cells (HUVECs) was evaluated. The results showed that SRP inhibited the production of ROS and NO, which involve the NADPH oxidase, and Keap1/Nrf2 signaling pathway. This study demonstrated that SRP-PLGA-MS had the potential to develop sustained-release drugs for hypertension treatment.

The tripeptide Leu-Pro-Lys (LPK), derived from the Sipunculus nudus protein, was synthesized and studied to investigate its potential protective effect on bone formation. The effect and mechanism of LPK were analyzed through network pharmacology, bioinformatics, and experimental pharmacology. The study found that LPK at concentrations of 25 µg/mL and 50 µg/mL significantly increased ALP activity and mineralization in C3H10 cells. LPK also increased the expression of COL1A1 and promoted bone formation in zebrafish larvae. Network pharmacology predicted 148 interaction targets between LPK and bone development, and analysis of the protein-protein interaction network identified 13 hub genes, including ESR1, MAPK8, and EGFR, involved in bone development. Through KEGG enrichment pathways analysis, it was determined that LPK promotes bone development by regulating endocrine resistance, the relaxin signaling pathway, and the estrogen signaling pathway. Molecular docking results showed direct interactions between LPK and ESR1, MAPK8, and MAPK14. Additional verification experiments using western blot assay revealed that LPK significantly upregulated the expression of genes related to bone formation, including COL1A1, OPG, RUNX2, ESR1, phosphorylated MAPK14, and phosphorylated MAPK8 in C3H10 cells. These results suggest that LPK promotes bone formation by activating the estrogen/MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

IntroductionSipunculus nudus is the most known species in the genus Sipunculus, distributed in tropical and subtropical coastal waters.MethodsPacBio sequencing and Illumina sequencing were combined for whole-genome sequencing of S. nudus. LC-MS/MS analysis was performed for the metabolomics of S. nudus.ResultsHerein, we report a 1.75 Gb complete genome assembly with a contig N50 size of 450 kb of the S. nudus based on a strategy combining third-generation long-read sequencing and Illumina sequencing. A total of 80391 protein-coding genes are annotated in this genome. Furthermore, gene family evolution analysis shows that S. nudus belonged to Mollusca or was close to Mollusca, but distinct with Annelida. Transcriptome analysis indicates the involvement of complex developmental events in larve. KEGG pathway analysis of differentially expressed genes showed that these DEGs were mainly enriched in the pathway of amino acid metabolism, lipid metabolism and transport and catabolism. LC-MS/MS analysis shows that S. nudus was rich in a variety of nutritional and functional components, such as carnitine, free amino acids, unsaturated fatty acids, inosine and methionine sulfoxide. Combined transcriptome with LC-MS/MS analysis, the results showed that gene expression and metabolic level involved in the inosine, arginine and proline biosynthesis of S. nudus during different growth stages were significantly changed.DiscussionOur genome assembly provides an important genome resource and new insight into the relationships of Sipuncula to other spiralian phyla. Meanwhile, transcriptome and LC-MS/MS analysis reveal the systematic gene expression profiles and metabolite components of S. nudus during different growth stages, which provide new insight into the exploration and development of bioactive molecules of S. nudus.

The peanut worm (Sipunculus nudus) is an important economic and ecological fishery resource in China. To determine how S. nudus interacts with its culture environment, in this study, the diversity, composition, and interrelationships of bacterial communities in the intestine, coelomic fluid, and culture environment of S. nudus through high-throughput sequencing using the Illumina HiSeq sequencing platform. Alpha diversity analysis showed that the highest bacterial community richness and diversity were found in the sediments. Species annotation revealed that Proteobacteria dominated in all samples (48.92%–58.36%), and the other dominant phyla were highly variable, indicating a certain independence between the environment and the composition of the bacterial community of S. nudus. The coelomic fluid of S. nudus contained high concentrations of Bacillus and could be a source of potential probiotic bacteria for isolation and culture. Cluster and operational taxonomic unit Venn diagram analyses showed that the bacterial community composition in the intestine was more similar to that in the sediments compared with water. The predicted functional analysis of bacterial communities indicated that the functions of bacterial communities in the different surrounding environment were highly similar and involved in various aspects, such as membrane transport, amino acid metabolism, carbohydrate metabolism, and replication and repair. Our findings have important implications on the establishment of sustainable microecological regulation and management strategies for S. nudus culture and provide a reference for the development and utilization of probiotic bacteria.

To form a stable emulsion system, the water-soluble proteins (WSPs) of Sipunculus nudus were prepared as the sole effective stabilizer for the high internal phase emulsion (HIPEs), of which the influence of the WSPs concentration and environmental stability was investigated. The HIPEs were fabricated using a simple one-pot homogenization process (10,000 rpm/min, 3 min) that involved blending the WSPs (0.1, 1, 2, 3, 4, and 5 wt%) with soybean oil (60, 65, 70, 75, 80, 85, and 90%). The microstructure and properties of stable HIPEs were characterized by particle size, ζ-potential, visual observations, optical microscopy, and dynamic rheology property measurements. As the concentration of WSPs increases, the mean particle diameter of HIPEs decreases, on the contrary, the apparent viscosity and storage modulus gradually increase. At a given emulsifier concentration (3 wt%), the stable and gel-like HIPEs were formed at the oil internal phase (ϕ) values of 70–75%, all the pH range in values from 3 to 9, and the ionic strength from 100 to 500 mM. Furthermore, the HIPEs that were stabilized formed a gel-like state that was relatively stable to heat and storage (30 days). And there was a new phenomenon that the destabilized HIPE of the freeze-thaw treatments could still return to a gel-like state again after homogenizing. The study results suggest that the WSPs of S. nudus as a natural emulsifier could be widely used in the food industry.

The peanut worm (Sipunculus nudus) is an economically important fishery resource in China. To determine how dietary carbohydrate and protein levels affect the growth performance of juvenile S. nudus and identify the mechanisms underlying observed patterns, five isoenergetic and isolipidic diets with different levels of carbohydrate and protein were formulated and fed to juvenile S. nudus; the experimental groups were referred to as EG1, EG2, EG3, EG4, and EG5, respectively. After 90 days of feeding, S. nudus had significantly lower survival rates when fed D5 compared with other diets (P < 0.05), and the highest survival rate was observed in EG2 individuals. The weight gain rate and specific growth rate were significantly higher in EG2 compared with the other groups (P < 0.05). Metabolomic profiling using liquid chromatography–mass spectrometry revealed 83 significantly differential metabolites (POS: 59; NEG: 24), which were identified via an in-house MS2 database. Pathway analysis indicated that the significantly different metabolites were involved in 22 metabolic pathways (POS: 9; NEG: 13), including tyrosine, phenylalanine, and tryptophan biosynthesis; phenylalanine metabolism; D-glutamate and D-glutamine metabolism; proline and arginine metabolism; aspartate, alanine, and glutamate metabolism; and aminoacyl-tRNA biosynthesis. These analyses implied that the biosynthetic capabilities of juvenile S. nudus were greater in the EG2. The results of this research enhance our understanding of the effects of dietary carbohydrate and protein levels on the growth performance of juvenile S. nudus.