Objective To investigate the efficacy and adverse reactions of half-dose glucocorticosteroid and cytoxan,combined with leflunomide for the treatment of lupus nephritis (LN) of MRL/lpr mice,and provide experimental evidences for LN therapy.Methods Twenty-eight 10-week-old MRL/lpr mice were randomly divided into four groups:Group A,blank control group; Group B,classical control group; Group C,full-dose control group; Group D,half-dose treatment group,with 7 mice in each group.The therapeutic efficacy and side reactions in the four groups were observed and compared before and 12 weeks after treatment.Statistical analysis was conducted with one-way ANOVA,q test and Pearson's correlation analysis.Results The serum anti-double stranded DNA (anti-dsDNA) antibody titers (0.43±0.16,0.32±0.09,0.44± 0.18,1.95±0.19) U/ml,serum creatinine level (1.63±0.63,0.40±0.23,0.82±0.21,10.86±2.17) mg,24-hour urine protein excretion level (71±8,60±5,68±3,121±10) μmol/L and renal pathological changes in group B,C,D were significantly improved than those of the group A (P＜0.05) after 12 weeks treatment.There was no significant difference in the efficacy between group B,C,and D (P＞0.05).The incidence of adverse reactions in group D was significantly lower than that in other groups (P＜0.05).Conclusion Multi-target therapy,such as half-dose prednisone and CTX,combined with leflunomide can effectively control lupus disease activity with less side effects.This regimen is cheap,safe and effective for the treatment of LN in MRUL/lpr mice.This study has provided animal evidences for this multi-target therapy for LN.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans