The effects of stereotactic body radiotherapy on peripheral natural killer and CD3~+CD56~+ NKT-like cells in patients with hepatocellular carcinoma

Background: Both natural killer(NK) and CD3+CD56+ natural killer T(NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy(SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma(HCC), and to identify possible surface markers on these cells that correlate with the prognosis. Methods: Twenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γand TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis. Results: The peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+ NK cells before SBRT and higher percentage of CD158b + NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3+CD56+ NKT-like cells was associated with a higher overall survival rate in HCC patients. Conclusions: SBRT has an apparent effect on both peripheral NK and CD3+ CD56+ NKT-like cells. Lower percentage of NKp30 + NK cells before SBRT and higher percentage of CD158b + NK cells after SBRT are correlated with poor patients' PFS. Higher percentage of CD3+ CD56+ NKT-like cells is associated with higher OS in HCC patients.

T cell–associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model

Although oxymatrine(OMT) has been shown to directly inhibit the replication of hepatitis B virus(HBV) in vitro, limited research has been done with this drug in vivo. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection.The infection was achieved by tail vein injection of a large volume of DNA solution. OMT(2.2, 6.7 and20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen(HBs Ag), hepatitis B e antigen(HBe Ag)and hepatitis B core antigen(HBc Ag). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir(ETV) in the elimination of serum HBs Ag and intrahepatic HBc Ag. Inaddition, OMT accelerated the production of interferon-γ(IFN-γ) in a dose-dependent manner in CD4^+T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.

LjaFGD:Lonicera japonica functional genomicsdatabase

Lonicera japonica Thunb.,a traditional Chinese herb,has been used for treating human diseases for thousands of years.Recently,the genome of L.japonica has been decoded,providing valuable information for research into gene function.However,no comprehensive database for gene functional analysis and mining is available for L.japonica.We therefore constructed LjaFGD(www.gzybioinformatics.cn/LjaFGD and bioinformatics.cau.edu.cn/LjaFGD),a database for analyzing and comparing gene function in L.japonica.We constructed a gene co-expression network based on 77 RNA-seq samples,and then annotated genes of L.japonica by alignment against protein sequences from public databases.We also introduced several tools for gene functional analysis,including Blast,motif analysis,gene set enrichment analysis,heatmap analysis,and JBrowse.Our co-expression network revealed that MYB and WRKY transcription factor family genes were co-expressed with genes encoding key enzymes in the biosynthesis of chlorogenic acid and luteolin in L.japonica.We used flavonol synthase 1(LjFLS1)as an example to show the reliability and applicability of our database.LjaFGD and its various associated tools will provide researchers with an accessible platform for retrieving functional information on L.japonica genes to further biological discovery.

Humoral immunity, the underestimated player in hepatitis B

Over decades,the immunological research of hepatitis B virus(HBV)infection has focused on HBVspecific T cells.In chimpanzees acutely infected with HBV,the deletion of CD4+or CD8+T cells causes chronic HBV infection.In humans,the HBV-specific T-cell response is temporally correlated with serum HBV clearance during an acute HBV infection,whereas HBVspecific T cells are both quantitatively and qualitatively defective in chronic HBV patients.