1.Mechanism and research progress of cancer treatment by α-therapy combined with immunotherapy
Mengqin ZHU ; Mengdie YANG ; Fei YU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(7):424-427
Alpha-particles, which have strong cytotoxicity, could reduce radiation damage to surrounding tissues, and stimulate anti-tumor immune response, so they have good development prospect in cancer treatment. The current researches show that α-emitting radionuclides increase the presentation of major histocompatibility complex-I (MHC-Ⅰ) on tumor cells and induce immunogenic cell death (ICD) to activate immune response mediated by CD8 + T cells. As two methods of α-therapy, α radioimmunotherapy and diffusing α-emitters radiation therapy (DART) further enhance the anti-cancer effect when combined with immunotherapy. The methods of immunotherapy include adoptive cell therapy (ACT), immune checkpoint blockade, neutralization of immunosuppressive cells and immunoadjuvant. This article reviews the characteristics of α-particles for cancer treatment, the mechanism of immune response induced by ionizing radiation (including α-radionuclides) and the related research of α-therapy combined with immunotherapy.
2.Effect of bluetongue virusinfection on type Ⅰ interferon response in BHK-21 cells
Shimei LUO ; Yunyi CHEN ; Qisha LI ; Yanmei ZHOU ; Yifei WANG ; Xinyu LIAO ; Xuer-Ou HU ; Yuanjian WEI ; Mengqin LI ; Meng ZHU ; Xun ZHANG ; Beirui CHEN ; Xianping MA ; Jiarui XIE ; Meiling KOU ; Haisheng MIAO ; Fang LI ; Huashan YI
Chinese Journal of Veterinary Science 2024;44(8):1639-1644,1690
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.
3.Improvement effects of Runchang granules on the constipation in mice and its mechanism
Mengqin HUANG ; Xuesong WANG ; Yuhan GAN ; Shiqin LU ; Qiqi DENG ; Qing ZHU ; Jiao GUO
China Pharmacy 2024;35(2):160-165
OBJECTIVE To investigate the improvement effects of Runchang granules on the constipation in mice and its potential mechanism. METHODS The mice were randomly divided into normal control group, model group, Runchang granules low-dose and high-dose groups (5, 10 g/kg), mosapride group (0.003 g/kg, positive control), with 6 mice in each group. The latter 4 groups were given loperamide intragastrically (0.004 g/kg), twice a day, for 3 consecutive days. Normal control group and model group were given purified water intragastrically, and administration groups were given relevant medicine intragastrically for 7 consecutive days. After the last medication, fecal moisture content and intestinal motility of mice were determined, while the structures of colon and ileum, and the secretion of colonic mucus were observed. Protein expressions of tyrosine kinase receptor (c-kit), mucin 2 (MUC2) and stem cell factor (SCF) were determined in colon; meanwhile, the mRNA expression levels of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, inducible nitric oxide synthase (iNOS)] as well as factors related to promoting intestinal motility [neuronal nitric oxide synthase (nNOS), smooth muscle myosin light chain kinase (smMLCK), 5-hydroxytryptamine 4 receptor (5-HT4R), MUC2, SCF, c-kit] were determined. RESULTS Compared with model group, the fecal water content, intestinal propulsion rate, protein expression of c-kit in colon, relative expressions of MUC2 and SCF protein, and mRNA expressions of factors related to promoting intestinal motility (except for nNOS and SCF in Runchang granules low-dose group) were all increased significantly in Runchang granules low-dose and high-dose groups, and mosapride group (P<0.05 or P<0.01). mRNA expression levels of inflammatory factors were decreased significantly(P<0.05 or P<0.01). Both colon and ileum injuries improved, and the secretion of colon mucus was increased significantly in Runchang granules high-dose group (P<0.01). CONCLUSIONS Runchang granules have laxative effect and can improve constipation in mice, and its mechanism may be related to the promotion of the secretion of colon mucus and MUC2 expression, and the activation of SCF/c-kit signaling pathway.