Objective: To study the effect of siRNA on multidrug resistance1(MDR1) gene expression in KBv200 cells. Methods: MDR1-siRNA was synthesized and transfected into KBv200 cells.The MDR1 mRNA and P-gp were assayed by RT-PCR and flow cytometry.Cytotoxicity was determined by a tetrazolium-based chemosensitivity assay(MTT).Cellular accumulation of Dox was measured by fluorescence spectrophotometry. Results: MDR1-siRNA decreased MDR1 mRNA and P-gp expression(P

According to the base complementation, the principle antisense technology is the sequence specific binding of complementary antisense nucleic acids or their chemical modification to the nucleic acids in cells, resulting in the suppression or prevention of gene translation. For the treatment of cancer, a lot of antisense drugs have been designed, which target the genes involved in the pathogenesis of cancer. And some of them have been in clinical trials. The author reviewed the progress of the clinical trials of these antisense drugs.

Carcinoma ; drug therapy ; genetics ; metabolism ; pathology ; radiotherapy ; Desmoplastic Small Round Cell Tumor ; metabolism ; pathology ; Diagnosis, Differential ; Gene Rearrangement ; Head and Neck Neoplasms ; drug therapy ; genetics ; metabolism ; radiotherapy ; Humans ; Keratin-20 ; metabolism ; Keratin-7 ; metabolism ; Lymphatic Metastasis ; Male ; Mediastinal Neoplasms ; drug therapy ; genetics ; metabolism ; radiotherapy ; Melanoma ; metabolism ; pathology ; Neuroectodermal Tumors, Primitive ; metabolism ; pathology ; Nuclear Proteins ; genetics ; metabolism ; Oncogene Proteins ; genetics ; metabolism ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Rhabdomyosarcoma ; metabolism ; pathology ; Thymus Neoplasms ; drug therapy ; genetics ; metabolism ; radiotherapy

Objective To explore the clinical curative effect of early enteral nutritional support for acute se-vere organophosphorus pesticide poisoning.Methods 56 cases with acute severe organophosphorus pesticide poison-ing were selected and divided into group A and group B in accordance with the random number table.Both groups were given conventional emergency treatment.Enteral nutrition support with nutrition pump was applied for 30 cases of group A in 48 -72hours,while group B in 72h -5d.The time of consciousness recovery,CHE increase to normal 60%,the incidence rate of intermediate syndrome,gastrointestinal complications of abdominal pain,abdominal disten-sion,vomiting,reflux,diarrhea,VAP,MODS of the two groups of patients were compared.Results The time of con-sciousness recovery (3.6 ±0.8)d in group A was lower than that of group B(4.1 ±0.6)d (t=2.612,P<0.01), the CHE increase to normal 60%(5.5 ±1.3)d in group A was lower than that of group B(6.3 ±1.1)d(t=2.464, P<0.05),the incidence rate of intermediate syndrome(3.3%)in group A was lower than that of group B(38.5%) (χ2 =4.691,P<0.05),the VAP of 13.3% in group A was lower than that of group B(46.2%)(χ2 =7.352,P<0.01),the MODS of 13.3% in group A was lower than 38.5% of group B(χ2 =4.691,P<0.05),the duration in ICU of (8.0 ±1.2)d in group A was lower than (12.0 ±2.4)d of group B(t=7.705,P<0.01).There was no sig-nificant difference of gastrointestinal complications between the two groups (P >0.05 ).There was no significant difference of gastrointestinal complications between the two groups (P>0.05).Conclusion Early enteral nutritional support is effective and safe for acute severe organophosphorus pesticide poisoning and worthy of promotion.

ObjectiveTo investigate the effects of hyperbaric oxygen therapy on T-lymphocytes 1 and cytokines including IL-6, IL-10 and TNF-α asindicators well representing immune function and inflammation in normal rats and rats with systemic inflammatory response syndrome. Methods Forty Sprague-Dawley male Rats were randomly ( random number) divided into five groups.Rats of group A were treated by saline solution (0.9 ％ NaCl,5 mL/kg),and served as control group; rats of group B were treated with saline solution and hyperbaric oxygen therapy three times; rats of group C were treated with zymosan (500 mg/kg) ; rats of group D were treated with zymosan and hyperbaric oxygen therapy once; and rats of group E were treated with zymosan and hyperbaric oxygen therapy three times.At 24 hours after saline or zymosan administration,rats were sacrificed and blood samples were collected from the portal vein.CD3 +,CD4+,CD8+ cells were counted by flow cytometer,and plasma levels of IL-6,IL-10 and TNF-αwere measured by ELISA.The results were analyzed by one - way ANOVA and LSD post-hoc test.Results CD4 T cell of normal rats was decreased by hyperbaric oxygen (P＜0.01 ),CD4/CD8 T cell ratio was also decreased ( P ＜ 0.05 ).Of rats with zymosan administration,CD4 T cells and CD8 T cells were both decreased on a parallel (P＜0.01 ).A single one HBO and HBO for three times both raised the percentage of CD4 T cells which was significantly decreased by zymosan administration ( P ＜ 0.01 and P ＜ 0.05 ).In rats without hyper- inflammation,hyperbaric oxygen therapy showed a pro-inflammatory effect by elevating TNF-α (P＜0.01),IL-6 (P＜0.05) and reducing 1L-10 (P＜0.05).ConclusionsHBO reduces CD4 T cells in normal rats.HBO reduces the production of TNF-α,IL-6 and IL-10 during hyper- inflammation.HBO is pro - inflammatory in normal rats and minor SIRS rats withourt appreciable hyper-inflammation in circulation.

Objective To investigate whether host derived immune-deficient dendritic cells (DC) were capable of inducing immunological tolerance to islet xenografts and to ascertain its mechanism. Methods Immune-deficient DC were obtained from marrow of BALB/C mice by inductive differentiation,and loaded with MHC antigen of Wistar rat. The loaded DC were injected into diabetic model mice through tail vein,and,7 days later, islet of Wistar or SD rats were implanted beneath the renal capsule. Survival time of grafts was monitored. Mixed lymphocyte culture and TH1/TH2 cytokine expression were observed. Results Compared to the untreated mice, the survival time of Wistar islets was significantly prolonged in the pretreated mice(P

Objective To investigate whether TGF-?_1 gene modified dendritic cells could induce immune tolerance in islet xenotransplantation. Methods Mature and immature DC were cultured from bone marrow of BALB/C mice, and then transfected the immature DC with TGF?_1 gene. Two kinds of DC were loaded with antigen of islet from Wistar rats, and injected into BALB/C mice with diabetes. After one week, the islets of Wistar or SD rats were transplanted under the capsular of left kidney. Survival time of grafts, proliferation and cytotoxicity of host T cell were evaluated. Results Grafts survival time in normal group was (10.2?1.1)d, (7.0?1.3)d in mature DC pretreated group (P0.05. The proliferation and cytotoxicity of T cell were enhanced in mature DC pretreated group (SI=6.92, KRmax=73%, P

Objective To investigate the inducible effect of immature dendritic cells (DC) on immune tolerance in coordination islet xenotransplantation.Methods Mature and immature DC were cultured from BALB/c mice with 20 ?g/L GM-CSF and 500 ?g/L GM-CSF+ 200 ?g/L IL-4, respectively, then loaded with major histocompatibility complex (MHC) antigen of Wistar rat. Mature and immature DC were injected into the mice with diabetes. After a week, the islets of Wistar rat or SD rat were transplanted under the envelop of left renal of the diabetes mice. The survival time of grafts was monitored. The immune reactivity of T cell was evaluated by mixed lymphocyte culture. Results Grafts in BALB/c mice pretreated with mature DC rejected quickly, while the survival time of grafts was significantly prolonged in the mice pretreated with immature DC. However, whether pretreated with mature DC or immature DC, grafts from SD rat were rejected soon. The splenocytes of tolerant mice showed mild proliferation. Conclusion The recipient pretreated with immature DC will lead to the anergy of T lymphocyte, and prolong the survival time of xeno-islet.

Objective:To investigate the effect of host derived immune deficient dendritic cell(DC) on immune tolerance in transplantation of xenoislet.Methods:Mature or immune deficient DC were cultured from BALB/c mice and loaded with MHC antigen of Wistar rat. The DC were injected into the diabetes mice through tail venous, then islets of Wistar or SD rats were implanted beneath the capsule of renal after one week. Survival time of grafts was monitored. Mixed lymphocyte culture and Th1/Th2 cytokine were performed.Results:Surviving time of Grafts in normal group was 8.2?1.1 d, and that of mature DC treated group was 6.1?1.1 d(P

AIM: To study the effect of group Ⅱ and Ⅲ metabotropic glutamate receptors (mGluRs) agonists on 1-methyl-4-phenylpyridinium (MPP~+)-induced glutamate uptake inhibition in C6 glioma cells. METHODS: The glutamate uptake into astrocytes was measured by using radio-ligand binding assay method. RESULTS: It was shown that Group Ⅱ mGluRs agonist (2' S, 2' R, 3 ' R) -2- (2', 3 ' -dicarboxycyclopropyl) glycine (DCG-Ⅳ) (100 ?mol?L~(-1)) and Group Ⅲ mGluRs agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) (100 ?mol?L~(-1)) significantly reversed MPP~+-induced glutamate uptake inhibition. Furthermore, the enhancement effects of DCG-Ⅳ and L-AP4 were blocked by their respective antagonists, (RS)-1 -Amino-5-phosphonoinan-1-carboxylic acid (APICA) and (RS)-?-methylserine-O-phosphate (MSOP). CONCLUSION: Group Ⅱ and Ⅲ mGluRs agonists produce neuroprotective effects by enhancing the activity of glutamate transporters.