This study was to evaluate the cellular inhibition effects induced by anti-AGR2 monoclonal antibody 18A4 in two AGR2-negative melanoma cells, A375 and B16-F10, treated with external oncoprotein AGR2. MTT assay and colony formation assay were performed to detect the cell proliferation rate. Flow cytometry analysis was performed to evaluate cell cycle transition. Cell migration rate was analyzed by wound healing assay. Cell morphological changes were detected by phalloidin staining. The expression of p53 was detected by Western blotting and immunofluorescence. Results showed that 18A4 inhibited the AGR2-dependent tumor properties including enhanced proliferation, accelerated cell cycle, increased cell migration and morphological changes of cells. In addition, by Western blot analysis and immunofluorescence, AGR2 blocking antibody 18A4 also restored p53 expression that was repressed by external AGR2 treated by chemotherapeutic drug doxorubicin. These findings suggest that 18A4 is able to inhibit the cellular tumorigenic properties induced by external AGR2 and is a potential drug against fumor.

Objective:To investigate the effects of Bifidobacterium animalis subsp. lactis BB-12 on hippocampal neuroinflammation and cognitive function of mice after whole brain radiotherapy. Methods:A total of sixty male C57BL/6J mice aged 7-8 weeks were randomly divided into 5 groups with 12 mice in each group: control group (Con group), probiotic group (BB-12 group), irradiation group (IR group), irradiation and Memantine group (IR+ Memantine group), irradiation and probiotic group (IR+ BB-12 group). The model of radiation-induced brain injury of mice was established by 10 Gy whole brain radiotherapy with a medical linear accelerator. Y-maze test was used to evaluate the cognitive function. The activation of microglia and astrocytes was observed by immunofluorescence staining. The expressions of inflammatory cytokines interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected by quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR) and Western blot.Results:Y-maze test showed that, compared with Con group, the percentage of the times of reaching the novel arm in the total times of the three arms decreased significantly in the IR group ( t=5.04, P<0.05). BB-12 mitigated radiation-induced cognitive dysfunction ( t=4.72, P<0.05). Compared with Con group, the number ( t=3.05, 7.18, P<0.05) and circularity index ( t=6.23, 2.52, P<0.05) of Iba1 and GFAP positive cells were increased, the microglia and astrocytes were activated in the hippocampus of IR group, but these alterations were eliminated by BB-12. After whole brain IR, the mRNA and protein expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α in the hippocampus of mice were significantly increased compared with Con group ( tmRNA =4.10, 3.04, 4.18, P<0.05; tprotein=11.49, 7.04, 8.42, P<0.05), which were also significantly reduced by BB-12 compared with IR group ( tmRNA=4.20, 3.40, 2.84, P<0.05; tprotein=6.36, 4.03, 3.75, P<0.05). Conclusions:Bifidobacterium animalis BB-12 can suppress neuroinflammation mediated by microglia and astrocytes in the hippocampus of mice after radiotherapy and alleviates IR-induced cognitive dysfunction. Therefore, BB-12 has potential application in alleviating radiation induced brain injury.

Objective To study the effect of SLCO1B1 521 T>C and APOE gene polymorphisms on the clinical efficacy and safety of atorvastatin in ischemic stroke patients with dyslipidemia. Methods 210 cases of ischemic stroke with dyslipidemia were enrolled from April 2018 to December 2018 to determine SLCO1B1 521 T>C and APOE gene polymorphisms. Patients received atorvastatin 20 mg/d orally. TC, TG, HDL-C, LDL-C levels were measured to evaluate the efficacy 3 months pre-and post- treatment. TBil, ALT, AST, CK levels were assayed with following up adverse reactions to evaluate safety. Results SLCO1B1 521 T>C genotype distribution was TT79.05%, TC19.05%, CC1.90%. E2, E3, E4 allele frequencies of APOE genes were 14.28%, 67.62%, 18.10%. Each genotype conforms to the law of Hardy-Weinberg balance. After three months of medication, there were significant differences in TC, TG, LDL-C, HDL-C changes in patients with different APOE genotypes. No obvious abnormality was found in safety index. The incidence of myalgia in SLCO1B1521 T>C mutant group was significantly higher than that in the wild group (P<0.01). Conclusion Lipid regulation of atorvastatin was affected by APOE gene polymorphism. SLCO1B1521 T>C may be associated with myalgia, the adverse reaction of atorvastatin. The detection of SLCO1B1 and APOE genotyping is helpful for individualized treatment of blood lipids and provides basis for rational use of statins in patients for drug therapy management.