In recent decades,in silicoabsorption, distribution, metabolism, excretion (ADME), and toxicity (T) modelling as a tool for rational drug design has received considerable attention from pharmaceutical scientists, and various ADME/T-related prediction models have been reported. The high-throughput and low-cost nature of these models permits a more streamlined drug development process in which the identification of hits or their structural optimization can be guided based on a parallel investigation of bioavailability and safety, along with activity. However, the effectiveness of these tools is highly dependent on their capacity to cope with needs at different stages, e.g. their use in candidate selection has been limited due to their lack of the required predictability. For some events or endpoints involving more complex mechanisms, the currentin silicoapproaches still need further improvement. In this review, we will briefly introduce the development ofin silicomodels for some physicochemical parameters, ADME properties and toxicity evaluation, with an emphasis on the modelling approaches thereof, their application in drug discovery, and the potential merits or deficiencies of these models. Finally, the outlook for future ADME/T modelling based on big data analysis and systems sciences will be discussed.

Cluster of differentiation (CD) antigens are cell surface molecules expressed on leukocytes and other cells associated with the immune system. Antibodies that react with CD antigens are known to be one of the most essential tools for identifying leukocyte subpopulations. T lymphocytes, as an important population of leukocytes, play essential roles in the adaptive immune system. Many of the CD antigens expressed on T lymphocytes are used as surface markers for T lymphocyte classification, including CD3, CD4 and CD8 molecules. In this review, we summarize the recent advances in the identification of CD molecules on T lymphocytes in teleosts, with emphasis on the functions of CD markers in the classification of T lymphocyte subsets. We notice that genes encoding CD3, co-receptors CD4 and CD8 have been cloned in several fish species and antibodies have been developed to study protein expression in morphological and functional contexts. T lymphocytes can be divided into CD4⁺and CD8⁺cells discriminated by the expression of CD4 and CD8 molecules in teleost, which are functionally similar to mammalian helper T cells (Th) and cytotoxic T cells (Tc), respectively. Further studies are still needed on the particular characteristics of teleost T cell repertoires and adaptive responses, and results will facilitate the health management and development of vaccines for fish.

Outer membrane protein C of Edwardsiella tarda is a major cell surface antigen and it was identified to be an immunogenic protein by Western blot using flounder (Paralichthys olivaceus) anti-recombinant OmpC (rOmpC), and anti-E. tarda antibodies. rOmpC tested the immune protective effect against E. tarda challenge in a flounder model and produced a relative percentage of survival rate of 85%. The immune response of flounder induced by rOmpC was investigated, and the results showed that: (1) the levels of specific serum antibodies induced by rOmpC were significantly higher than the control group after the second week after immunization, and the peak level occurred at week five after immunization; (2) rOmpC could induce the proliferation of sIg+ lymphocytes, and the peak levels of sIg+ lymphocytes in blood, spleen, and pronephros occurred at 4–5 weeks after immunization; and (3) the MHCIIα, CD4-1, IL-1β, IL-6 and TNF-α genes were significantly induced after being injected with rOmpC. Taken together, these results demonstrated that rOmpC could evoke highly protective effects against E. tarda challenge and induce strong innate immune response and humoral immune response of flounder, which indicated that OmpC was a promising vaccine candidate against E. tarda infection.