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Liza haematocheila is exposed to various chemical contaminants from anthropogenic sources, including tributyltin chloride (TBTC). Yet the toxicity mechanism of TBTC on haarder remains unclear. The haarder was exposed to different doses (0, 10%, 20%, and 50% of LC 50 -96 h) of TBTC. In this study, the results revealed its high bioaccumulation in the livers and significant alteration for development. The activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase decreased after 96-h exposure to TBTC, this accompanied by an increased malondialdehyde level. TBTC exposure caused the intense production of reactive oxygen species, a reduction in total blood cell count in serum, and apoptosis-related alterations in livers, indicating that enhanced oxidative stress occurred in the process of TBTC exposure. Histological results revealed angiorrhexis and infiltration of inflammatory cells, vacuolar degeneration of hepatocytes in the livers, and swelling, fusion, and disintegration of gill organs. Interestingly, the obtained transcriptional profiles indicated that high doses of TBTC caused energy disorder, apoptosis, and adipogenesis restriction mediated by cytokines and adipokines in Jak-STAT and adipocytokine signaling pathways. In summary, acute exposure to high doses of TBTC could impair the antioxidant system and pathways related to energy, apoptosis and adipogenesis, eventually posing a serious challenge to the fitness of haarder individuals and its fish populations as marine resources. [Display omitted] • Tributyltin chloride (TBTC) bioaccumulated highly in haarder livers. • Apoptosis was induced by TBTC in haarder livers. • TBTC caused transcriptome changes in haarder livers. • TBTC caused energy disorder and adipogenesis restriction in haarder. [ABSTRACT FROM AUTHOR]

Tetrabromobisphenol A (TBBPA) and lead (Pb) are widely used in industrial field, which poses a serious threat to human and animal health. In particular, a large volume of wastewater containing TBBPA and Pb was discharged into the aquatic environment, causing a seriously negative impact on fish. Currently, whether TBBPA and Pb have a synergistic toxicity on fish remains unclear. In this study, we used the grass carp hepatocytes (L8824 cell line) exposed to either TBBPA or Pb, or both to determine their potential impacts on fish. The results showed that Pb or TBBPA induced oxidative stress and the loss of mitochondrial membrane potential in grass carp hepatocytes. In contrast to the control cells, the levels of JAK2, p -JAK2, STAT3 and p-STAT3 were significantly upregulated after exposure to TBBPA and Pb. Furthermore, the levels of Caspase3, Caspase9 and Bax were all increased while the level of Bcl2 was decreased in hepatocytes exposed to TBBPA or Pb. Results of flow cytometry and AO/EB staining reveled significant increases in the number of apoptotic cells in the TBBPA and Pb group compared to the controls. Notably, cells exposed to both TBBPA and Pb exhibited more severe damage than the single exposure, manifested by a higher number of apoptotic cells in the co-exposure group than the single exposure groups. Nevertheless, N-acetyl- l -cysteine (NAC) treatment could remarkably alleviate oxidative damage and loss of membrane potential in grass carp hepatocytes induced by TBBPA and Pb. Altogether, our study showed that combined exposure of TBBPA and Pb has a synergistic toxicity due to, inducing oxidative stress to activate JAK2/STAT3 signaling pathway, resulting in apoptosis of carp hepatocytes. This study shed a new light on the toxicological mechanism of exposure of TBBPA and Pb and provided a potential treatment of toxicity induced by TBBPA and Pb. [Display omitted] • TBBPA and Pb had synergistic effects. • TBBPA and Pb exposure induced oxidative stress. • TBBPA and Pb exposure activated JAK2/STAT3 signaling pathway. • TBBPA and Pb exposure caused apoptosis. [ABSTRACT FROM AUTHOR]

Caspase-associated recruitment domain (CARD) containing proteins play critical roles in molecular interaction and regulation of various signaling pathways, such as the activation of caspase and NF-κB singling pathway in the process of apoptosis or inflammation. In the present study, a novel CARD containing protein (designed Cg CARDCP-1) was identified and characterized from oyster Crassostrea gigas . Molecular feature analysis revealed that, the open reading frame (ORF) of Cg CARDCP-1 gene was 759 bp encoding a polypeptide of 253 amino acids with a conserved N-terminal CARD domain and two transcriptional coactivator p15 (PC4) domains in C-terminus. Homologous alignment showed that the amino acid sequence of Cg CARDCP-1 shared 30%–46% identity with that of caspase-2. By RT-PCR detection, the mRNA transcripts of Cg CARDCP-1 were found to be widely distributed in various tissues of oyster with the highest expression level in hemocytes and mantle. And Cg CARDCP-1 protein was mostly distributed in the cytoplasm of oyster hemocytes as shown by immunohistochemistry. Moreover, the Cg CARDCP-1 mRNA expression level in hemocytes was significantly up-regulated after lipopolysaccharide (LPS) and Vibrio splendidus stimulations. The recombinant Cg CARDCP-1 displayed strong binding activity with LPS in vitro . In addition, after transfected into the HEK-293T cell with luciferase reporter system, Cg CARDCP-1 could significantly promote the NF-κB activation (1.29-fold, p  < 0.05) compared to that in the control group. These results collectively demonstrated that the Cg CARDCP-1 might serve as a recognition molecule for LPS and a regulator of NF-κB activation in the immune response of oyster. [ABSTRACT FROM AUTHOR]

Hirame novirhabdovirus (HIRRV) is a fish rhabdovirus belonging to family Rhabdoviridae, genus Novirhabdovirus , which is highly contagious and virulent, and causes hemorrhagic disease in many fish species. In the present work, the whole genome sequence of HIRRV strain CNPo2015 that previously isolated from cultured flounders was obtained using high-throughput sequencing. It consists of 10,998 nucleotides and encodes six viral proteins arranged in order of 3′-N-P-M-G-NV-L-5′. Among Novirhabdovirus , L protein of CNPo2015 possessed the lowest amino acid sequence divergence with HIRRV isolate CA 9703 and HIRRV 080113, and the highest with Snakehead rhabdovirus. Furthermore, the immune response of Hirame natural embryo (HINAE) cell line to HIRRV infection was characterized by RNA-seq, and the results showed that 1976 differentially expressed genes (DEGs) including 1219 up-regulated and 727 down-regulated genes were identified in the HINAE cells infected with HIRRV at 48 h post infection (hpi). Several KEGG pathways were significantly enriched in the viral infected cells, such as cytokine-cytokine receptor interaction, JAK-STAT signaling pathway, cell cycle, apoptosis, RIG-I-like receptors signaling pathway and P13K-AKT signaling pathway. Post viral infection, the flow cytometric Annexin V/PI assay found that apoptotic rate of HINAE cells showed a slight increase within 3 days and then the early and late apoptotic rate were significantly increased to 41 ± 2.65% and 12.37 ± 2.61% at day 4, respectively. Meanwhile, qRT-PCR results also showed that six apoptosis-related genes (BCL2L1, CASPASE 3, CASPASE 10, FAS, AKT and CDK1) were significantly upregulated. This investigation has not only enriched our knowledge of sequence difference characteristics between CNPo2015 and other Novirhabdoviruses , but also provided a data basis for deeper understanding of immune responses in flounder cells post viral infection. • Genome sequence of HIRRV strain CNPo2015 was obtained and compared with other Novirhabdoviruses. • The immune response of HINAE cells to HIRRV infection was systematically characterized by RNA-seq. • HIRRV infection upregulated apoptotic genes and induced cellular apoptosis of HINAE cells. [ABSTRACT FROM AUTHOR]

Koumine is an alkaloid with significant anti-anxiety, anticancer cell proliferation, and analgesic activities, and our previous studies have shown that koumine can be used as an immunostimulant in aquaculture, but the molecular mechanism of its effect remains unclear. We fed a basal diet with 0, 0.2, 2, and 20 mg/kg koumine to C. carpio for 10 weeks, and comprehensive studies of the histological and biochemical parameters and transcriptomes of the four groups were performed. Histological results indicated that the number of apoptotic cells in the liver increased with increasing koumine concentration. Compared with those of the control group, the malondialdehyde, superoxide dismutase, catalase, acid phosphatase, alkaline phosphatase, and lactate dehydrogenase levels of the treatment group increased to varying degrees. In total, 100.11 GB of clean data, 4774 DEGs, and 138 differentially expressed genes were obtained from the transcriptome data. Differentially expressed genes were classified into 187 signalling pathways, and the circadian rhythm signalling pathway, the JAK-STAT signalling pathway, the p53 signalling pathway and the PPAR signalling pathway were the top enriched pathways. The qRT-PCR results confirmed that the key genes ifnar1 , socs3l , epoa , ghra , cMyc , mcl-1 , shisa4 , and gtse1 involved in balancing cell proliferation and apoptosis were enriched in these pathways. We discovered that the JAK-STAT and p53 pathways are important targets of koumine. Such information contributes to a better understanding of the potential mechanism by which koumine regulates hepatic immunity as well as to lays the theoretical foundation for its application. [Display omitted] • Dietary koumine elevated the level of apoptosis in Cyprinus carpio liver cells. • Dietary koumine can effectively activate the antioxidant protective and the drug metabolic of the Cyprinus carpio liver. • The JAK-STAT and p53 pathways play an important role in the regulation of liver apoptosis by koumine subunits. [ABSTRACT FROM AUTHOR]