ABSTRACT
In a growing multidrug-resistant environment, the identification of potential new drug candidates with an acceptable safety profile is a substantial crux in pharmaceutical discovery. This review discusses several aspects and properties of approved marine natural products derived from ascidian sources (phylum Chordata, subphylum Tunicata) and/or their deduced analogues including their biosynthetic origin, (bio)chemical preclinical assessments and known efficacy-safety profiles, clinical status in trials, but also translational developments, opportunities and final conclusions. The review also describes the preclinical assessments of a large number of other ascidian compounds that have not been involved in clinical trials yet. Finally, the emerging research on the connectivity of the ascidian hosts and their independent or obligate symbiotic guests is discussed. The review covers the latest information on the topic of ascidian-derived marine natural products over the last two decades including 2022, with the majority of publications published in the last decade.
Subject(s)
Biological Products , Urochordata , Animals , Biological Products/therapeutic use , Pharmaceutical PreparationsABSTRACT
Crangon crangon bacilliform virus (CcBV) was first discovered in 2004 in European brown shrimp (Crangon crangon) caught along the English coast. This study describes a duplex PCR assay developed for the detection of CcBV, based on amplification of the lef-8 gene (211â¯bp) of CcBV and the E75 gene (105â¯bp) of C. crangon as an internal amplification control. The lef-8 and E75 primer pairs were designed based on preliminary genome sequencing information of the virus and transcriptomic data available for C. crangon, respectively. Sequencing of the resulting amplicons confirmed the specificity of this PCR assay and sequence analysis of the lef-8 fragment revealed amino acid identity percentages ranging between 31 and 42% with members of the Nudiviridae, proposing that CcBV may reside within this family. Finally, the duplex PCR assay was applied to samples of C. crangon hepatopancreas tissue collected along the Belgian coast to screen for the presence of CcBV. The prevalence of CcBV averaged 87%, which is comparable to previous reports of high prevalence, based upon histological analysis, in shrimp collected along the English coast. Development of a specific and sensitive PCR assay to detect CcBV will provide a useful tool for future aquaculture and research programs involving C. crangon.
Subject(s)
Crangonidae/virology , DNA Viruses , Polymerase Chain Reaction/methods , Animals , DNA, Viral/analysisABSTRACT
The chemical status of five dredged spoil disposal sites in the Belgian Part of the North Sea is evaluated. A linear mixed-effect model was applied to PCB, PAH and heavy metal data from 2005 to 2014. No decrease in PCB concentrations was found, with even an increase at two disposal sites. Hg/AL ratios increased with 62% at one disposal site (BR&WS2) from 2005 to 2006 to 2013-2014. Cu and Zn concentrations increased at two disposal sites. Additional harbour sampling suggests that the latter is possibly linked to antifouling paints. Based on OSPAR environmental assessment criteria, the current chemical status of the sites suggests no chronic effect of dredged spoil disposal. However, increasing time trend data for PCB, Hg, Cu and Zn demonstrate the importance of monitoring to identify adverse trends.
Subject(s)
Environmental Monitoring , Geologic Sediments/analysis , Metals, Heavy/analysis , Belgium , North SeaABSTRACT
The decapod Crangon crangon is one of the most valuable European fisheries commodities. Despite its economic importance, little sequence data is available for this shrimp species. In this paper, we report the transcriptome sequencing for five different stages of C. crangon (early embryo, late embryo, larva, female adults and male adults) and the annotation and stage-specific expression analysis of nuclear receptors (NRs) and RNA interference (RNAi)-related genes. The NRs are transcription factors that play an essential role in growth, development, cell differentiation, molting/metamorphosis and reproduction, while the RNAi-related genes are very important for internal gene expression regulation and in antiviral defense. We discovered a NR in the female C. crangon which is either a very rapidly evolved homolog of HR10, or a novel NR altogether. This new NR could act as a biological marker for sex determination as it is not expressed in male adults. Most RNAi-related genes were present in C. crangon, proving that the requirements for successful RNAi is present in this decapod shrimp. RNAi-based applications in Crangon such as its use in functional genomics or as antiviral therapeutics could become very important in the near future.
Subject(s)
Crangonidae/genetics , Gene Expression Profiling , Gene Expression Regulation, Developmental , RNA Interference/physiology , Receptors, Cytoplasmic and Nuclear/genetics , Amino Acid Sequence , Animals , Female , Male , Molecular Sequence Data , Phylogeny , Sequence Homology, Amino AcidABSTRACT
Decapod crustaceans are characterized by multiple ecdysteroid receptor (EcR) and retinoid-X-receptor (RXR) isoforms, which likely exhibit variant dimerization and transactivation interactions. In the brown shrimp C. crangon we cloned C-terminally truncated CrcEcR and CrcRXR isoforms and isoforms exhibiting deletions within the hinge region. For the former, in silico modeling of the CrcEcR indicated that, where the conserved helices H10 and H11 of the ligand-binding domain (LBD) are missing, an alternative C-terminal α-helix repairs the ligand-binding pocket (LBP). The truncated CrcRXR isoforms lack a major part of the LBD (H4-H12), thereby compromising ligand binding and dimerization. Through an in vitro ecdysteroid responsive reporter assay, we showed that these natural receptor variations do not impair receptor functioning but probably alter the receptor dimerization preferences. By the same in vitro assay, using full-length CrcEcR and CrcRXR, the effect of tributyltin (TBT) on ecdysteroid-induced transactivation was evaluated. The transactivation by 10nM PonA was reduced with 64% by 20 nM TBT. In silico modeling confirmed that TBT fits in the full-length CrcRXR-LBD. Furthermore, semi-quantitative PCR indicated altered expression of CrcEcR and CrcRXR isoforms after in vivo acute exposure to TBT, especially in the ovaries.
Subject(s)
Crangonidae , Receptors, Steroid/chemistry , Receptors, Steroid/metabolism , Retinoid X Receptors/chemistry , Retinoid X Receptors/metabolism , Trialkyltin Compounds/pharmacology , Amino Acid Sequence , Animals , Cell Line , Crangonidae/drug effects , Crangonidae/genetics , Crangonidae/metabolism , Drosophila melanogaster , Drug Resistance/drug effects , Drug Resistance/genetics , Drug Resistance/physiology , Ecdysteroids/chemistry , Ecdysteroids/genetics , Ecdysteroids/metabolism , Gene Expression Regulation/drug effects , Models, Biological , Models, Molecular , Molecular Sequence Data , Multiprotein Complexes/chemistry , Multiprotein Complexes/drug effects , Multiprotein Complexes/metabolism , Multiprotein Complexes/physiology , Protein Conformation , Protein Isoforms/chemistry , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Isoforms/physiology , Protein Multimerization/drug effects , Protein Multimerization/physiology , Receptors, Steroid/genetics , Retinoid X Receptors/genetics , Retinoid X Receptors/physiology , Transcriptional Activation/drug effects , Transcriptional Activation/physiology , Transfection , Water Pollutants, Chemical/pharmacologyABSTRACT
cDNAs encoding ecdysteroid receptor (EcR) and retinoid X receptor (RXR) were cloned and sequenced from brown shrimp Crangon crangon (Crustacea: Decapoda), a common faunal species and commercially important in the North-West European coastal waters. A 3D model of the ligand-binding domain (LBD) of EcR was created and docking of ponasterone A (PonA) was simulated in silico. Finally, we report the transfection of expression plasmids for these receptors in the mutant Drosophila L57-3-11 cell line. Through an ecdysteroid responsive reporter assay we clearly prove the functionality of shrimp ecdysteroid receptor in the transfected L57-3-11 cell line. Our results indicate that the Drosophila L57-3-11 cell line and in silico LBD modeling can be used to study the function of crustacean ecdysteroid receptors and be applied to assess endocrine disrupting effects on non-target crustacean species.
Subject(s)
Crangonidae/metabolism , Receptors, Steroid/chemistry , Receptors, Steroid/metabolism , Amino Acid Sequence , Animals , Cell Line , Drosophila , Ecdysterone/analogs & derivatives , Ecdysterone/chemistry , Ecdysterone/metabolism , Molecular Sequence Data , Phylogeny , Protein Structure, Secondary , Receptors, Steroid/classification , Receptors, Steroid/genetics , Retinoid X Receptors/chemistry , Retinoid X Receptors/metabolism , Sequence Homology, Amino AcidABSTRACT
The paper reports the concentrations and patterns of CBs in sediments of the Belgian part of the southern North Sea and the Scheldt estuary for the period 1991-2001. The long-term analytical performance was well within the quality assurance boundaries set at the outset of the study and is consistent with the state of the art for this type of analysis. The CB concentrations (given as the median of the sum of IUPAC Nos 28, 52, 101, 118, 138, 153 and 180) vary between 0.1 microg kg(-1) and 50 microg kg(-1) dry weight in the total sediment and it could be demonstrated that CB patterns in the fine fraction of the sediment were closely similar throughout the investigated area. Isolation of the fine fraction (<63 microm) by sieving can be regarded as a physical normalisation to reduce the differences in sediment granulometric composition. It allows for a better understanding of CB distribution and patterns and improves the trend analysis. A significant downward trend could not be found at any of the stations, which suggests that CB levels have not been changing in the area of interest in the past decade.
