Effects of PI3K / Akt signaling pathway on the autophagy of rat alveolar macrophages exposed to dust / 中国职业医学

OBJECTIVE: To determine the regulating role of phosphatidylinositol 3-kinase( PI3K) / protein kinase B( Akt)signaling pathway in the autophagy activity of rat NR8383 cells exposed to silicon dioxide( SiO_2). LY294002 was used to block PI3 K pathway. METHODS: i) The normal NR8383 cells were used and divided into blank group and silica exposure group( final concentrations of SiO_2 suspension were 0 and 50 mg / L respectively). They were cultured for 3,6,12,20 and24 hours. The enzyme linked immunosorbent assay( ELISA) was used to assess the amount of tumor necrosis factor-α( TNF-α) and transforming growth factor-β1( TGF-β1) in supernatants of cultured cells,and then the optimal time of cells exposed to dust was determined. ii) NR8383 cells were divided into control group( treated with a same volume of F-12 K medium without serum),silica group( treated with SiO_2 suspension,final concentration 50 mg / L) and intervention group( treated with SiO_2 suspension and PI3 K inhibitor LY294002,final concentration 50 mg / L and 20 μmol / L,respectively).Cells were harvested following incubation. ELISA was used to detect the levels of TNF-α and TGF-β1 at the time point of20 hours after incubation. To reveal the autophagy status of cells,Western blotting was used to detect Akt and microtubuleassociated proteins 1 light chain 3( LC3) protein at time point of 20 hours; laser scanning confocal microscope( LSCM)was used to observe the immunofluorescence expression of autophagy at time points of 3,6,12 and 20 hours. The cells were also treated with the lysosomal inhibitor chloroquine diphosphate( CDP) at the same time of SiO_2 treatment. RESULTS: i) The time point of 20 hours was confirmed to be the best dust exposure time for in vitro cell model of NR8383 cells.ii) The levels of TNF-α and TGF-β1 of supernatant in the silica group were higher than those of the control group( P <0. 05). The levels of TNF-α and TGF-β1 of supernatant in the intervention group were higher than those of the control group and silica group( P < 0. 05). The Akt protein expression of the intervention group was lower than those in the control group and the silica group,respectively. The LC3 Ⅱ / Ⅰ protein level of the silica group was higher than those of the control group and intervention group( P < 0. 05),but no statistical significance was found between the control group and intervention group( P > 0. 05). LSCM results indicated that autophagy expression at time points of 3 and 6 hours were stronger than those of 12 and 20 hours in control group; autophagy expression at time point of 12 hours was stronger than those of 3 and 6 hours in the silica group,while the autophagy expression at time point of 20 hours was slightly weaker than that of 12 hours,but still stronger than those of 3 and 6 hours. Compared with the same time point in control group,autophagy expression at 3 and 6 hours were weaker in the silica group,while the expressions increased obviously at time points of 12 and 20 hours. Autophagy expression at all time points decreased in the intervention group compared with silica group,especially at the time point of 20 hours. The autophagy expression in each group increased in varying degrees after added with CDP blocking. CONCLUSION: Silica dust exposure can induce autophagy in rat NR8383 cells. PI3 K inhibitor LY294002 can reduce the autophagy expression indicating that the PI3 K / Akt signaling pathway might participate in the autophagy process of silica dust inducing autophagy in alveolar macrophages.

The anti-inflammatory and the analgesic effects of vitacoxib, a new molecular entity / 中国药学杂志

OBJECTIVE: To study the anti-inflammatory and analgesic effects of vitacoxib. METHODS: The in vitro COX-1 and COX-2 inhibitory activities of vitacoxib were tested in human whole blood assay as well as canine whole blood assay. The anti-inflammatory and analgesic effects of vitacoxib were evaluated in several in vivo models including croton oil induced mouse ear endema, carrageenan-induced rat paw swelling and mouse acetic acid writhing model. RESULTS: In vitro assay, vitacoxib has potent inhibitory COX-2 activity and selectivity for COX-2 over COX-1. In vivo anti-inflammatory experiments, vitacoxib has significant inhibitory activities both in croton oil-induced mouse ear oedema model test(P < 0.01) and the carrageenan-induced rat paw swelling test(P < 0.05). In vivo analgesic effect experiments, vitacoxib has significant inhibitory activity on acetic acid-induced writhing pain in mice (P < 0.05). CONCLUSION: Vitacoxib, a selective COX-2 inhibitor, demonstrates excellent anti-inflammatory activity in both in vitro and in vivo models tested.

Targeting the substrate binding domain of polo-like kinase 1: advances in the study of PBD1 inhibitors / 药学学报

Polo-box domain 1 (PBD1) is a characteristic domain of polo-like kinase 1 (PLK1), which locates in C-terminal and can influence the catalytic activity and specific subcellular locations of PLK1. At present, most PLK1 inhibitors are developed to occupy the ATP pocket or its close sites. However, this kind of PLK1 inhibitors is difficult to pursue target selectivity and may encounter cross drug resistance with other kinase inhibitors due to the conserved sequence of ATP pocket. Recently, PBD1, with aberrant specificity in sequence and structure, has attracted enormous interests as the alternative target to the discovery of corresponding inhibitors for anti-tumor drugs. The structure and function of PBD1 as well as the advances of its inhibitors are reviewed in this paper.

Clinical Significance of Detection of S - 100? Protein in Cerebrospinal Fluid and Serum of Children with Acute Viral Encephalitis / 实用儿科临床杂志

Objective To explore the changes of S - 100? protein in cerebrospinal fluid and serum of children with viral encephalitis and its clinical significance. Methods The levels of S - 100? protein of cerebrospinal fluid and serum of 36 children with viral encephalitis and 20 lumbar anesthesia children without central nervous system diseases were measured by enzyme - linked immunosor bent assay. Differences in the levels of cerebrospinal fluid and serum S-100? protein between children with and without coma, with and without convulsion, with and without sequelae in the case group were compared. Results S-100? protein levels of cerebrospinal fluid in the case group and control group were (0.641?0.390) and (0.037 ? 0.014) ?g/L( P