ABSTRACT
JS001 (toripalimab) is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1 (PD1). In this study, we used a different iodine isotype (I) to label JS001 probes to target the human PD1 (hPD1) antigen. , the half maximal effective concentration (EC) value of I-JS001 did not significantly differ from that of JS001. The uptake of I-JS001 by activated T cells was 5.63 times higher than that by nonactivated T cells after 2 h of incubation. The binding affinity of I-JS001 to T cells of different lineages after phytohemagglutinin (PHA) stimulation reached 4.26 nmol/L. Humanized C57BL/6 mice bearing mouse sarcoma S180 cell tumors were validated for immuno-positron emission tomography (immuno-PET) imaging. Pathological staining was used to assess the expression of PD1 in tumor tissues. The homologous Ihuman IgG (IhIgG) group or blocking group was used as a control group. Immuno-PET imaging showed that the uptake in the tumor area of the I-JS001 group at different time points was significantly higher than that of the blocking group or the I-hIgG group in the humanized mouse model. Taken together, these results suggest that this radiotracer has potential for noninvasive monitoring and directing tumor-specific personalized immunotherapy in PD1-positive tumors.
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Objective BALB/c mutant curly mice and normal BALB/c mice were genetically detected by microsatellite DNA marker analysis to detect the differential microsatellite loci between BALB/c mutant curly mice and normal mice.Methods 38 microsatellite DNA loci were selected and their variation in the BALB/c mutant curly mice, BALB/c mutant hairless mice and normal BALB/c mice were detected by multiplex fluorescence PCR and STR scanning genotyping.Results There were 27 the same microsatellite loci between the 38 microsatellite loci in BALB/c mutant curly mice and normal mice,and there were 11 differential loci, with a mutation rate of 28.9%(11/38). There were 30 the same sites between BABL/c mutant hairless mice and normal mice,and there were 8 different loci,with a mutation rate of 21.1%(8/38). There were also 12 differential loci between BABL/c mutant curly mice and hairless mice. Conclusions BALB/c mutant curly mice have a higher mutation rate and are significantly higher than those of hairless mice,demonstrating that the mutations in curly mice and hairless mice are two completely different mutations. These results provide reliable theoretical data for the future study and development of BALB/c mutant curly mice.
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Objective To study the effects of simple portal hypertension on the endotoxin levels in serum and intestinal mucosa of rats. Methods A total of 16 rats were divided into the blank control group (4 rats) and the model groups (3-day group, 7-day group and 10-day group, 4 rats in each group). The rat model of partial portal vein ligation was established in the model groups, and samples of blood and jejunum, ileum and colon of the rats were taken on the 3rd, 7th and 10th days, respectively. Changes in the serum endotoxin levels were detected by ELISA. Histopathological changes of the intestinal tissues were examined by HE staining. Results The rat model of partial portal vein ligation was successfully established in all the model groups. The serum levels of endotoxin on the 3rd, 7th and 10th days in the model groups were not significantly different from that in the normal control group. Damages of different intestinal segments were not serious on the 3rd day after modeling. However, on the 7th day after modeling, there were some sowllen and damaged intestinal villi in the intestinal mucosa of each intestinal segment, and the connection between the epithelial cells and the lamina propria was broken, compared with that at 3 days after modeling. In addition, there were obvious damages in the intestinal mucosa and lamina propria on the 10th day, compared with that at 3 d and 7 d after modeling. Conclusions In the case of normal liver function, portal hypertension can cause intestinal mucosal damages within a short period of time, but the amount of endotoxin produced by intestine does not exceed the processing capacity of the liver and thus does not cause an increase in the serum endotoxin level.
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Objective To establish a chemiluminecentdetection method ( CLIA ) of HCV IgG antibody for the detection of HCV infection and therefore lay a foundation for the research and development of testing kit.Methods Based upon the indirect ELISA method, the microwell plate was coated with HCV-NS3 and HCV-Core antigen expressed through gene engineering, and the anti-human IgG antibody was labeled with horse radish peroxidase.In this way, the chemiluminesent detection method of HCV IgG antibody was established.Meanwhile, the serum specimen of randomly selected 198 patients infected with HCV from No.302 Hospital of PLA and 222 blood donors, and the results were compared.Results The HCV-IgG antibody, a positive consistent rate of 99.0%( 196/198 ) , a negative consistent rate of 98.2%(218/222), and a total consistent rate of 98.6%(414/420) were found through testing 420 serum specimen with self-made agent and contrast agent.One HCV positive serum was repetitively tested with the self-made agent for 10 times, and a coefficient of variation ( CV) of less than 10% was found.Conclusion The chemiluminescent detection method of HCV IgG antibody is initially established, and the method, with an outstanding specificity and sensitivity, is applicable for screening blood donors, clinically detecting HCV infection as well as epidemiological survey.
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Objective To investigate if there are differences in hematological indexes between BALB/c mutant curly mice and normal BALB/c mice.Methods 6 week old BALB/c mutant curly and normal BALB/c mice of each 20 ( male and female) were selected, and 8 blood routine indexes and 15 serum electrolytes and biochemical indexes were detected using automatic blood cell analyzer and automatic biochemical detection, and the results of two groups were compared.Results The sex and group results of WBC,MCV,PLT and MCHC between BALB/c mutant curly mice and normal mice have significant differences ( P <0.05, P<0.01 );the sex and group results of Na+、K+and Cl-between BALB/c mutant curly mice and normal mice have significant differences( P<0.05,P<0.01);the sex and group results of ALT、GLU and TG between BALB/c mutant curly mice and normal mice have significant differences(P<0.05,P<0.01). Conclusion Some hematological indexes between BALB/c mutant curly and normal BALB/c mice are different clearly, and these results will provide the theoretical references for researching and using mutant curly mice model.