Four novel compounds, chaephilone C (1), chaetoviridides A–C (2–4), were obtained from the culture of a deep sea derived fungus Chaetomium sp. NA-S01-R1, together with four known compounds—chaetoviridin A (5), chaetoviridine E (6), chaetomugilin D (7) and cochliodone A (8). Their structures, including absolute configurations, were assigned based on NMR, MS and time-dependent density functional theory (TD-DFT) ECD calculations. A plausible biogenetic pathway for compounds 1–3 was proposed. Compounds 2 and 3 exhibited antibacterial activities against Vibrio rotiferianus and Vibrio vulnificus. Compounds 1, 3 and 4 displayed similar anti-methicillin resistant Staphylococcus aureus (anti-MRSA) activities in comparison to chloramphenicol. Compound 2 showed the most potent cytotoxic activities towards the Hep G2 cell and compounds 1 and 3 demonstrated relatively stronger cytotoxic activities than the other compounds against the HeLa cell.
A novel iridovirus, Cherax quadricarinatus iridovirus (CQIV), was identified from diseased C. quadricarinatus in 2014. This virus is considered as a new threat to crustacean aquaculture because it is lethal to both peneaid shrimp and crayfish. Here, we determined the complete genome sequence of CQIV. The double-stranded DNA genome is 165 695 bp in length with a G+C content of 34.6 %. A total of 178 open reading frames (ORFs) have been predicted, encoding hypothetical proteins ranging from 50 to 1327 amino acids. Forty-seven of these exhibit similarities to proteins of known functions. Phylogenetic analysis based on multiple alignments of conserved proteins shows that CQIV clusters with the members of the family Iridoviridae, but is placed in a distinct clade from all the five known genera. It indicates that CQIV may represent a new genus in the family Iridoviridae, for which we propose the name Cheraxvirus based on the host organism.
Chemotherapy is commonly used for the treatment of lung cancer, but strong side effects and low treatment efficacy limit its clinical application. Here, extracellular vesicles (EVs) as natural drug delivery carriers were used to load conventional anticancer drug doxorubicin (DOX) and a chemosensitizer lonidamine (LND). Two types of EVs with different sizes (16k EVs and 120k EVs) were prepared using different centrifugation forces. We found that co-delivery of DOX and LND with both EVs enhanced the cytotoxicity and reduced the dose of the anticancer drug significantly in vitro. Effective delivery of anti-cancer drugs to cancer cells was achieved by direct fusion of EVs with the plasma membrane of cancer cells. On the other hand, DOX and LND inhibited cancer cell proliferation by increasing DNA damage, suppressing ATP production, and accelerating ROS generation synergistically. DOX and LND loaded EVs were also applied to the mouse lung cancer model and exhibited significant anticancer activity. In vivo study showed that smaller EVs exhibited higher anticancer efficiency. In conclusion, the co-delivery of the anticancer drug and the chemosensitizer with EVs may have potential clinical applications for cancer therapy.
Two previously unreported citrinin dimer derivatives, penicitol D (1) and 1-epi-citrinin H1 (2), were isolated from the culture of a deep sea-derived fungus Penicillium citrinum NLG-S01-P1, together with 11 biogenetic related compounds (3–13). A plausible biogenetic pathway for compounds 2–4 was proposed. Their structures, including absolute configurations, were established through analysis of extensive spectroscopic data and time-dependent density functional theory (TD-DFT) ECD calculations. Compounds 1 and 2 showed antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA). Compounds 5 and 10 displayed relatively stronger activities than the other compounds against Vibrio vulnificus and Vibrio campbellii. Compound 1 showed the most potent cytotoxic activity towards the HeLa cell.
Despite the central role of hemocytes in crustacean immunity, the process of hemocyte differentiation and maturation remains unclear. In some decapods, it has been proposed that the two main types of hemocytes, granular cells (GCs) and semigranular cells (SGCs), differentiate along separate lineages. However, our current findings challenge this model. By tracking newly produced hemocytes and transplanted cells, we demonstrate that almost all the circulating hemocytes of crayfish belong to the GC lineage. SGCs and GCs may represent hemocytes of different developmental stages rather than two types of fully differentiated cells. Hemocyte precursors produced by progenitor cells differentiate in the hematopoietic tissue (HPT) for 3 ~ 4 days. Immature hemocytes are released from HPT in the form of SGCs and take 1 ~ 3 months to mature in the circulation. GCs represent the terminal stage of development. They can survive for as long as 2 months. The changes in the expression pattern of marker genes during GC differentiation support our conclusions. Further analysis of hemocyte phagocytosis indicates the existence of functionally different subpopulations. These findings may reshape our understanding of crustacean hematopoiesis and may lead to reconsideration of the roles and relationship of circulating hemocytes.