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Objective To investigate the role of miR-203 in radiation-induced thymic lymphoma (RITL).Methods A 60Co irradiator was used for total-body irradiation.MicroRNAs(miRNAs) level was assayed by qRT-PCR.Cell proliferation was assayed by MTT assay.Cell apoptosis was examined by fluorescence activated cell sorter (FACS).Dual luciferase reporter assay system was used to detect the 3'UTR reporter.Results MiR-203 was down-regulated in RITL tissues.Overexpression of miR-203 strongly inhibited the proliferation of both NIH3T3 cells and EL4 cells and vice versa.MiR-203 inhibited cells proliferation and induced apoptosis via TANK-binding kinase (TBK1),SLUG (SNAI2) and Cyclin D1 (CCND1).Conclusions Radiation down-regulated the level of miR-203 in thymic,which promoted radiation-induced thymic lymphoma by targeting TBK1,SNAI2 and CCND1.
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Objective:To explore the diagnosis and treatment of ketamine-associated urinary system dysfunction. Methods:Total-ly 56 cases of urinary tract symptoms with the history of ketamine abuse in recent years were retrospectively analyzed. The routine ex-amination and the examination related to the urinary system were given, and individual treatment was undertaken according to different situation. Results: The main symptom of ketamine-asscociated urinary tract dysfunction was lower urinary tract symptom (LUTS). Bladder pathologic biopsy showed different degree of inflammatory change. Imaging examination showed various degree of pathological changes, including reduced bladder capacity, thickened bladder wall, bladder contracture, ureteral stricture and hydronephrosis. Three patients had increased serum creatinine level. Conclusion: Ketamine-asscociated urinary system dysfunction is a disease with LUTS as the main clinical symptom. At the early stage, the disease is reversible with promising treatment outcome. In the progression of the disease, some patients develop irreversible histological changes in the urinary tract, which should be brought to the forefront.
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Background Researches indicated that etiology and epidemiology of pertussis toxin (PTX)dependent experimental autoimmune uveoretinitis(EAU)model are very different with human uveoretinitis owing to the influence of PTX on immune.Our previous study has established lipopolysaccharide (LPS),an endotoxin,which instesad of PTX,mediated EAU model.However,the exact roles of LPS and PTX in EAU still remained unclear.Objective This study was to investigate the roles of LPS and PTX in EAU model.Methods Twenty SPF C57BL/6(H-2b) mice were assigned to 0 d-PTX-EAU group,7 d-PTX-EAU group,0 d-LPS-EAU group and 7 d-LPS-EAU group using random number table method.The mice were immunized with interphotoreceptor retinoid-binding protein 1-20(IRBP 1-20) emulsified in complete Freund adjuvant (CFA),and concurrently with or on day 7 postimmunization,LPS or PTX was injected in the footpad or intraperitoneally respectively.Delayed-type hypersensitivity (DTH) of the mice was evaluated by measuring the ear thickness 48 hours after IRBP was injected into the ear pinna,and lymphocyte proliferation was assessed by tritiated thymidine uptake.Retinal histopathological examination was performed and scored based on criteria of Caspi.The use and care of experimental animals complied with Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results Serious infiltration of inflammatory cells,disorder of entire retinal structure and retinal folds were seen in the mice of the 0 d-PTX-EAU group and 7 d-LPS-EAU group on 21 days after injection of PTX or 14 days after injection of LPS,and severe vitritis and a few granuloma-like lesions were found in the 0 d-PTX-EAU group.However,only mild vasodilatation or less retinal folds were found in the 7 d-PTX-EAU group and 0 d-LPS-EAU group.The pathological scores in the mice of the 0 d-PTX-EAU group and 7 d-LPS-EAU group were higher than those of the 7 d-PTX-EAU group and 0 d-LPS-EAU group (all at P ＜ 0.05).The ear thickness was (62.600 ± 3.362) μm,(60.000±2.345) μm,(30.400± 1.817) μm and (32.800 ± 1.643) μm in the 0 d-PTX-EAU group,7 d-PTX-EAU group,0 d-LPS-EAU group and 7 d-LPS-EAU group,showing a significantly difference among the 4 groups (Fgroup =259.751,P=0.000),and the ear thicknesses of 0 d-PTX-EAU group and 7 d-PTX-EAU group were significantly higher than those of the 0 d-LPS-EAU group and 7 d-LPS-EAU group (all at P＜0.05).The lymphocyte proliferation was strongly enhanced in PTX-EAU groups,and the radiation count per minute (cpm) was (16 150.000±799.218)/min and (16 120.000±729.383)/min in the 0 d-PTX EAU group and 7 d-PTX EAU group,and (8 348.000±258.979)/min and (8 540.000±81.548)/min in the 0 d-LPS EAU group and 7 d-LPS EAU group respectively,with a significant difference among the PTX-EAU groups and LPS-EAU groups (Fgroup =316.978,P=0.000).Conclusions LPS and PTX play different roles during the EAU formation.LPS may be involved in the breakdown of blood-retina barriers (BRB).
ABSTRACT
Background The pathogenesis and management of human autoimmunity uveoretinitis is a focus in ophthalmology.For decades,a traditional experimental autoimmunity uveoretinitis (EAU) induced by pertussis toxin (PTX) was used for the basic investigation,which was thought to have a large deviation from the natural course of human autoimmunity uveoretinitis.Objective This study was to establish a new mice model of autoimmunity uveoretinitis which mimics the human autoimmunity uveoretinitis pathogenesis and offer a basis for the investigation and treatment of uveoretinitis.Methods Twenty 6-8 weeks old specific pathogen-free female C57BL/6 (H-2b) mice were randomized into normal control group,only endotoxin (lipopolysaccharide,LPS) induced uveitis group (endotoxin induced uveitis [EIU] group),interphotoreceptor retinoid-binding protein (IRBP1-20) +complete Freund adjuvant (CFA) induced uveoretinitis group (EAU group) and IRBP+CFA+LPS induced uveoretinitis group (LPS-EAU group).The mice of the EAU were only immunized with IRBP emulsified in CFA,and LPS-EAU group firstly were immunized with IRBP emulsified in CFA and then LPS was injected in the footpad of the mice on 7 days following immunization.The ocular pathological examination,histopathological scoring,delayed-type hypersensitivity and specific lymphocyte proliferating response were evaluated and compared with the EIU models,traditional EAU models without PTX and LPS-EAU models.The use and care of experimental animals complied with Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results No inflammatory response was found in the iris,cilliary body and retina of mice in the normal control group.However,mild blood vessels dilation and fibrin exudation were seen in the iris and cilliary body of mice in the EIU group.In the EAU group,mild vasculitis and swelling of nerve fiber layer were exhibited in the retinas; while in the LPS-EAU group,severe disorder of retinal structure,infiltration of inflammatory cells and damage of photoreceptor were found under the optical microscope.The pathological score was 0 in the models of the normal control group and EIU group,0.5 score in the EAU group and 3.0 scores in the LPS-EAU group,with a significant difference in the pathological scores between the EAU group and the LPS-EAU group (U=16.246,P =0.001).The earthickness of the mice was (35.60±0.55) μm in the LPS-EAU group,and this value was significantly higher than (12.60±0.55) μm of the EIU group (q =23.003,P＜0.01),but closed to (34.80±0.84) μm of the EAU group (t =0.820,P＞0.05).The obvious cloning were seen and theradiation count per minute was (8 540.00 ±54.77)/min in the model mice of the LPS-EAU group,and that in the EAU group was (8 484.00±47.75)/min,without significant difference between them (q =56.634,P =0.069).Compared with the β particle number (2 050.00±50.00)/min in the EIU group,that of the LPS-EAU group was significantly elevated (q =195.683,P =0.000).Conclusions LPS injection can induce EAU in mice,and this model can better imitate the pathogenesis of human autoimmunity uveoretinitis.