Adult ; Brain Diseases ; chemically induced ; Ethylene Dichlorides ; poisoning ; Female ; Humans ; Male ; Middle Aged ; Occupational Diseases ; chemically induced

Objective： To investigate the effect of oxLDL and VitE on the expression of CD40 and CD40 ligand(CD40L) in cultured human monoc ytes. Methods： The expression of CD40 and CD40L on monocytes su rface were measured by indirect immunorescence technique in combination with flo w cytometry. Results： Low concentration of oxLDL（≤200 μg/L） significantly increased the expression of CD40 and CD40L in a dose and time dep endent manner. High concentration (>200 μg/L）of oxLDL markedly reduced the exp ression of CD40 and CD40L. When VitE was added, it significantly reduced the ex pression of CD40 and CD40L on monocytes surface induced by oxLDL in a dose-depe ndent manner. Conclusion：It is an important mechanism that the high expression of CD40 and CD40L induced by oxLDL may be contributed to the for mation of atherosclerosis. Antioxidan VitE can partially inhibit the high expres sion of CD40 and CD40L on monocytes surface induced by oxLDL.

OBJECTIVETo evaluate the expression of microRNA (miR)-let-7b in peripheral blood cells of patients with primary biliary cirrhosis (PBC) and investigate its relationship to clinical disease parameters.

METHODSPeripheral blood and serum samples were obtained for study from 60 PBC patients and 60 healthy controls. Peripheral blood cells were extracted and subjected to real-time PCR to measure miR-let-7b expression. Serum levels of interleukin (IL)-18, total bilirubin (TBIL), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were measured by standard biochemical assays. The relationship between miR-let-7b expression and disease parameters was assessed by Spearman's rank correlation test.

RESULTSPBC patients showed significantly lower expression of miR-let-7b in peripheral blood cells than healthy controls (P less than 0.001); moreover, the miR-let-7b expression level decreased in parallel to increases in disease severity (stage I > II / III > IV). In PBC patients, the miR-let-7b expression was significantly correlated with Mayo risk scores (r = -0.4930, P less than 0.001), IL-18 (r = -0.4643, P less than 0.001) and ALP (r = -4119, P less than 0.001), but not with TBIL or GGT.

CONCLUSIONDecreased expression of miR-let-7b may be associated with development and progression of PBC, and this miRNA may represent a novel target of improved diagnostic and preventive strategies for PBC.

Adult ; Aged ; Alkaline Phosphatase ; blood ; Bilirubin ; blood ; Case-Control Studies ; Female ; Humans ; Interleukin-18 ; blood ; Liver Cirrhosis, Biliary ; blood ; Male ; MicroRNAs ; metabolism ; Middle Aged ; gamma-Glutamyltransferase ; blood

Adult ; Blood Platelets ; chemistry ; CD40 Antigens ; blood ; CD40 Ligand ; blood ; Cholesterol ; blood ; Female ; Humans ; Hypercholesterolemia ; blood ; drug therapy ; Male ; Middle Aged ; Simvastatin ; therapeutic use

OBJECTIVETo investigate the anti-inflammatory effect of erythropoietin (EPO) pretreatment on cardiomyocytes exposed to hypoxia/reoxygenation injury (H/R) and explore the possible mechanism.

METHODSThe cultured neonatal rats?ventricular cardiomyocytes were divided randomly into 4 groups, control group (C group), EPO pretreatment group (E group), EPO and pyrrolidine dithiocarbamate (PDTC) pretreatment group (EP group) and PDTC pretreatment group (P group). After 24 hours?pretreatment, the cardiomyocytes were exposed to H/R. After pretreatment and H/R, the expression of tumor necrosis factor-alpha(TNF-alpha) gene in all the groups was detected by RT-PCR and Western blot. The nuclear factor-kappa B (NF-kappa B) activity was detected by electrophoretic mobility shift assay (EMSA) and the inhibitor-kappa B alpha (I-kappa B alpha) protein level was detected by Western blot.

RESULTSThe decrement of I-kappa B alpha protein and the increasing NF-kappa B activity were found in cardiomyocytes pretreated with EPO before H/R compared to other groups (t equal to 3.321, 4.183, P less than 0.01). However, after H/R, NF-kappa B activity and expression of TNF-alphagene were significantly reduced, I-kappa B alpha protein expression was increased in cardiomyocytes of E group compared to other groups (t=3.425, 3.687, 3.454, P less than 0.01). All theses changes caused by EPO pretreatment were eliminated by the intervention of PDTC (an antagonist to NF-kappa B) during pretreatment.

CONCLUSIONSEPO pretreatment can inhibit the activation of NF-kappa B and upregulation of TNF-alpha gene in cardiomyocytes exposed to H/R through a negative feedback of NF-kappa B signaling pathway, and thus produces the anti-inflammatory effect. This might be one of the ways EPO produces the anti-inflammatory effect.

Analysis of Variance ; Animals ; Animals, Newborn ; Antioxidants ; pharmacology ; Blotting, Western ; Cells, Cultured ; Electrophoretic Mobility Shift Assay ; Erythropoietin ; pharmacology ; Hypoxia ; metabolism ; Inflammation ; drug therapy ; Myocytes, Cardiac ; drug effects ; metabolism ; NF-kappa B ; biosynthesis ; Pyrrolidines ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; Reperfusion Injury ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Thiocarbamates ; pharmacology ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; biosynthesis ; genetics

BACKGROUNDTo study the difference in gene expression between the EBV associated gastric carcinoma (EBVaGC) tissues. To explore the mechanism of gastric carcinoma pathogenesis initiated by EBV.

METHODSIn situ hybridization was used to study the frequencies of EBV small RNA expression in 155 cases of gastric carcinoma tissues. The expression levels of P53 protein and P21WAF1 protein were detected by immunohistochemistry in all gastric carcinoma tissues.

RESULTSThe expression of EBV small RNA was positive in 10 out of 155 cases (6.45%). The expression of P53 protein was weakly positive in 4 of the 10 cases. The expression level of P53 protein in EBVaGC was much lower than that in EBVnGC and was weakly positive in 30 of 145 cases with EBVnGC). P21WAF1 expression was detected in 7 of 10 cases with EBVaGC, but in 55 out of 145 cases with EBVaGC, P21WAF1 expression in EBVaGC was much higher than that in EBVnGC.

CONCLUSIONThere seems existing a special mechanism of pathogenesis in EBVaGC. In which P53 gene mutation may not play an important role.

Epstein-Barr Virus Infections ; metabolism ; pathology ; virology ; Herpesvirus 4, Human ; genetics ; physiology ; Host-Pathogen Interactions ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Proto-Oncogene Proteins c-met ; metabolism ; RNA, Viral ; genetics ; Stomach Neoplasms ; metabolism ; pathology ; virology ; Tumor Suppressor Protein p53 ; metabolism

Biomarkers, Tumor ; metabolism ; Carcinoma, Hepatocellular ; genetics ; metabolism ; CpG Islands ; Cyclin-Dependent Kinase Inhibitor p57 ; genetics ; metabolism ; DNA Methylation ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization ; Liver ; metabolism ; Liver Neoplasms ; genetics ; metabolism ; Polymerase Chain Reaction ; methods ; Promoter Regions, Genetic ; RNA, Messenger ; genetics ; metabolism

Objective： To investigate the effect of c ytokines (IFN-γ，TNF and IL-1) on the expression of CD40 and CD40 ligand (CD4 0L) in monocytes/macrophages. Methods： The mRNA expression of C D40 and CD40L was measured by RT-PCR and the CD40，CD40L expression on the mono cytes/macrophages were detected by flow cytometric analysis. Results： IFN-γ，TNF and IL-1 could not only significantly up-regulate the mRNA levels of CD40 and CD40L in cultured monocytes/macrophages, but also increase t he expression of CD40 and CD40L. Antioxidant VitE could reduce the expression o f CD40 and CD40L induced by IFN-γ，TNF and IL-1. Conclusion： IFN-γ，TNF and IL-1 can stimulate high expression of CD40 and CD40L . Antio xidant VitE can partially inhibit the expression of CD40 and CD40L induced by cy tokines in cultured monocytes/macrophages.

Adult ; Antigens, Differentiation, T-Lymphocyte ; blood ; Female ; Humans ; Liver Cirrhosis, Biliary ; blood ; pathology ; Male ; Middle Aged

OBJECTIVETo study the mechanism underlying the effect of combined use of cyclonpamine and hydroxycamptothecin in inducing the apoptosis of human oral squamous cell carcinoma cell line (OSCC) HSQ-89.

METHODSCCK8 assay was used to investigate the inhibitory effect of cyclopamine on HSQ-89 cells. Flow cytometry (FCM) was employed to examine the cell apoptosis following combined treatment with cyclonpamine and hydroxycamptothecin. Reverse transcription polymerase chain reaction (RT-PCR) was applied to detect the mRNA expressions of Bcl-2, Bcl-xl, and Bid in HSQ-89 cells after the treatments.

RESULTSCombined treatment with cyclonpamine and hydroxycamptothecin significantly inhibited the cell proliferation compared with hydroxycamptothecin treatment alone, also resulting in a significantly higher apoptosis rate of the cells (P<0.05). The mRNA level of Bcl-2 was significantly decreased after the treatments, especially after the combined treatment. Cyclopamine produced no significant effect on the mRNA levels of Bcl-xl and Bid in the cells.

CONCLUSIONThe combined use of cyclopamine and hydroxycamptothecin significantly down-regulates the expression on of bcl-2 to induce the apoptosis of human OSCC cell line HSQ-89.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Camptothecin ; analogs & derivatives ; pharmacology ; Carcinoma, Squamous Cell ; pathology ; Cell Line, Tumor ; Drug Synergism ; Humans ; Mouth Neoplasms ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Veratrum Alkaloids ; pharmacology