Circadian rhythms are endogenous 24 h variations found in virtually all physiological processes and behaviors, which are controlled by the transcriptional translational oscillator that consists of a series of core clock genes (bmal1, clock, cry and per) and clock controlled genes (rev-erbα, rorα, dbp, tef and hlf).Clock genes exist in immune organs, tissues and cells, leading to the immune cell function (migration and chemotaxis, phagocytosis, cytotoxicity and so on) and a variety of immune parameters (factor level of circulating immune cells and subsets of the relative and absolute number of cells) showing circadian rhythm changes, and playing an important role in maintaining immune homeostasis.In addition, some immune related diseases are closely correlated with circadian rhythms abnormalities.This paper will focus on the effect of circadian rhythms on immune functions and their roles in some immune related diseases.

Objective: To investigate which step of IL-6 signal transduction pathways in myeloma cells can be taken as the acting target of the antagonists for IL-6. Methods: EMSA and immunoprecipitation were used to detect the activation of transcription factors(TFs)-STAT3, NF-IL-6 and protein kinase ERK in a myeloma cell line-Sko-007 by IL-6. then anti-sense expression plasmids and anti-sense ODN for these signal moleculars were constructed and designed,the effects of these anti-sense nucleic acids on IL-6 signal transduction in Sko-007 cells were analyzed by the same methods. Results: IL-6 signal transduction could be antagonized by these anti-sense nucleic acids at different extent.Conclusion: TFs or protein kinases in IL-6 signal trareduction pathways can be taken as the target for antagonists design.

Objective To investigate effects of driving fatigue on auditory involuntary attention.Method Between-groups design was used.The control group included 13 taxi drivers after adequate rest while the fatigue group included 13 taxi drivers who had been driving for 10 h.Auditory oddball pattern was adopted.The standard stimulus was 800 Hz,probability 80%;target stimulus was 1 000 Hz,probability 10%;novel stimulus was sound generated by computer or other sound,probability 10%.Subjects were asked to press the mouse upon hearing the target sound.Result The distribution of P3a was mainly around the frontal-central area of the subjects in control group;the amplitude of P3a was evidently lowered in subjects after driving fatigue.Conclusion The ability of auditory involuntary attention declines after driving fatigue.

Objective　To investigate the IL-6 signal transduction pathways and their regulation mechanism in a human myeloma cell line-U266. Methods　Electrophoretic mobility shift assay (EMSA) was used to detect the activation of the transcription factors (TFs)-STAT3 and NF-IL-6 by IL-6. Cells were treated with chemical agents or transfected with the expression plasmids for the two TFs or the anti-sense oligonucleotide for protein kinase involved in one IL-6 signal transduction pathway. The change of the activation state of another IL-6 signal transduction pathway was also exhibited by EMSA. Results　Two IL-6 signal transduction pathways (JAK/STAT and Ras/NF-IL-6) can be activated by IL-6 of different dose in U266 cells. When one of the two signal transduction pathways was up-regulated, the other one was down-regulated. Conclusion　There is an antagonistic effect between the activation of two IL-6 signal transduction pathways in U266 cells.

Objective To investigate the effect of 36 h continuous sleep deprivation(SD) on circadian clock gene expression in the rat liver and kidney and the alteration of urine biomarker levels.Methods Twelve rats were randomly divided into control group and SD group.An SD device was used to deprive the rats of sleep.After 36 h continuous SD, the abdominal cavity was exposed to obtain livers and kidneys, and RT-PCR and Western blotting were used to detect expression of clock genes.Then,the pelvic cavity was exposed to obtain urine, and the changes in bio-marker total bile acids(TBA) were tested with ELISA.Results Compared with the control group, the mRNA level of liver clock and bmal1 was obviously reduced in the SD-treated rats (P<0.05).However, no obvious change was found in the samples from the kidney.Sharp down-regulation of CLOCK and BMAL1 protein expression was also observed in the rat liver after SD treatment.Urine TBA content in SD treated rats was raised obviously (P<0.001), compared with control.Conclusion Thirty-six hours of continuous SD could result in deregulation of circadian clock gene and cholesterol metabolism disorder in the rat liver.TBA might be used as a noninvasive biomarker of liver injury under SD stress conditions.

Drugs, Chinese Herbal ; Information Storage and Retrieval ; Medicine, Chinese Traditional

Objective To investigate the molecular mechanism of vascular endothelial growth factor ( VEGF) expression in bronchial epithelial cells (Beas-2B)induced by particulate matter 2.5(PM2.5).Methods PM2.5 powder was dis-solved in DMEM medium and diluted into five concentrations , 0,12.5,25,50 and 100μg/ml, respectively.The double an-tibiotics ( streptomycin and penicillin ) and FBS were added into the solution to a 2% final concentration of serum system after being treated by ultrasound for 30 minutes.The cultured Beas-2B cells were then treated with different doses of PM2.5.Subsequently, nuclear factor-kappa B(NF-κB) transactivity and the transcriptional activation of vegf gene promot-er were tested by dual-luciferase reporter gene analysis system while phosphorylation of p 65 , expression levels of IκBαand VEGF were detected by Western blotting .Results PM2.5 induced up-regulation of VEGF expression in Beas-2B cells in a dose-dependent manner , accompanied by NF-κB transactivation at the highest level under 100 μg/ml of PM2.5 treatment. Moreover, PM2.5 induced degradation of the repressor protein IκBαand increase in the phosphorylation level of p 65 sub-unit in Beas-2B cells.Knockdown of NF-κB p65 expression significantly inhibited vegf gene promoter transcriptional activa-tion as well as VEGF protein expression in Beas-2B cells induced by PM2.5.Conclusion PM2.5 induces VEGF expres-sion via activation of NF-κB pathway in bronchial epithelial cells .

Objective To explore the signal transduction mechanism of inhibitor kappa B kinase α( IKKα) , one of the catalytic subunits of IKK complex , for regulating p53 transactivation in the cellular ultraviolet radiation ( UVB) repsonse. Methods The transactivation of p53 was determined by dual-luciferase reporter gene analysis system while the expression and activation of IKKα, IKKβ, p53 and p38K was detected by Western blotting assay .Results UVB exposure induced activation and transactivation of p 53 in the wild type mouse fibroblasts ,but the effect was blocked by IKKa deficiency and recovered by reconstitution of IKKαexpression.Under the same conditions , IKKαregulated p38K activation, while inhibi-ting p38K activation down-regulated p53 transactivation under UVB exposure .Conclusion IKKαregulates UVB-induced phosphorylation and activation of p 53 in a p38K-dependent manner .

An enzyme linked immunosorbent assay ( ELISA ) and a flow cytometry assay ( FCA ) based on Wil2-S cells were developed and systematically compared for quantification of recombinant anti-CD20 humanized monoclonal antibody ( rh-anti-CD20zumab) in biological matrix. The specificity, precision and accuracy of each method at correspondingly different linear range showed good results. For ELISA, the precisions of intra-day and inter-day were both <19 . 5%, the relative error was from-18 . 2% to 17 . 6%;For FCA, the precisions of intra-day and inter-day were both <19. 0%, the relative error was from -18. 9% to 18. 4%. The sensitivity of ELISA was significantly higher than that of FCA. The quantitative ranges of ELISA and FCA methods were 0. 04-5. 0 mg/L and 3. 1-200 mg/L, respectively. The concentrations in serum samples and pharmacokinetics analysis were determined by both of two methods after vein drip administration of rh-anti-CD20zumab in rhesus monkeys. Pharmacokinetics data showed that there was excellent consistency between results obtained by two methods at the given dose. We believe that the novel FCA with high speed and high sensitivity can be used to perform PK and PD study of cell surface antigen-targeted antibody derivatives.

Aged ; Axilla ; Axillary Vein ; surgery ; Blood Vessel Prosthesis ; Breast Neoplasms ; complications ; pathology ; surgery ; Female ; Histiocytoma, Malignant Fibrous ; complications ; pathology ; surgery ; Humans ; Jugular Veins ; surgery ; Male ; Neoplasm Recurrence, Local ; Upper Extremity Deep Vein Thrombosis ; etiology ; surgery ; Vascular Grafting ; methods