Bellidifolin Inhibits Proliferation of A549 Cells by Regulating STAT3/COX-2 Expression and Protein Activity.

OBJECTIVES: Bellidifolin (BEL) is one type of tetraoxygenated xanthone that is particularly found in Swertia and Gentiana (Gentianaceae). Despite its broad range of pharmacological activities, it is still unclear whether BEL could be used for lung cancer treatment. Hence, we presently demonstrate the roles of BEL towards the proliferative inhibition of the prototypical A549 lung cancer cells. MATERIALS AND METHODS: The antiproliferative activity of BEL was initially verified by cellular experiments. A network pharmacology method was then pursued to assess BEL potential molecular targets from the platform for pharmacological analysis of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease enrichment of potential targets and construction of compound-target-disease network maps were performed based on a total of 20 diseases. Two core targets related to the BEL-mediated effect in A549 cells were obtained by importing potential targets into a protein-protein interaction database (STRING) and also analyzing respective data of related targets into this database. Last, these core targets were examined by in vitro analysis and molecular docking. RESULTS: CCK8 assays indicated that treatment with 50-100 µm BEL had an inhibitory effect on the proliferation of human A549 lung cancer cells, whereas this effect was time- and concentration-dependent. As control, treatment with 50-100 µm BEL did not inhibit the proliferation of normal lung epithelial cells (BEAS-2b cell line). H&E staining of BEL-treated A549 cells showed that, upon an increase of drug concentration, nuclear condensation and fragmentation were largely observed. Cell cycle analysis showed that in vitro treatment with 75-100 µm BEL could block A549 cells in S and G2 phases. Western blot analyses showed that after 72 hours of BEL treatment, the level of caspase-8/3 in A549 cells increased, and the level of PARP1 decreased in a dose-dependent manner. Network pharmacology analysis also indicated that lung cancer was the major disease susceptible to BEL treatment. At the same time, STAT3 and COX-2 were identified as two core targets of BEL in lung cancer treatment. Functional analyses further revealed that the cytotoxicity effect of BEL in A549 cells potentially involved the STAT3/COX-2 pathway. Moreover, molecular docking analysis indicated that BEL structure properly matches with COX-2 and STAT3 in space shape, thus illustrating the putative molecular mechanism of BEL's anticancer effect. CONCLUSIONS: Based on a series of in vitro analyses, network pharmacology, and molecular docking, the potential mechanism involving the antiproliferative and cytotoxic effects of BEL in lung cancer cells was investigated. Our study may help providing some theoretical basis for the discovery of novel phytotherapy drugs applicable for the treatment of lung cancer.

Mediating effect of mental elasticity on occupational stress and depression in female nurses / 中华劳动卫生职业病杂志

Objective@#To investigate the interaction between mental elasticityand occupational stress and depressionin female nurses and the mediating effect of mental elasticity, as well as the functioning way of mental elasticity in occupational stress-depression.@*Methods@#From August to October, 2015, cluster sampling was used to select 122 female nurses in a county-level medical institution as study subjects. The Connor-Davidson Resilience Scale (CD-RISC) , Occupational Stress Inventory-Revised Edition (OSI-R) , and Self-Rating Depression Scale (SDS) were used to collect the data on mental elasticity, occupational stress, and depression and analyze their correlation and mediating effect.@*Results@#The 122 female nurses had a mean mental elasticity score of 62.4±15.1, which was significantly lower than the Chinese norm (65.4±13.9) (P<0.05) ; the mean depression score was 41.0±7.7, which was significantly higher than the Chinese norm (33.5±8.6) (P<0.01) , and the incidence rate of depression of 52.5%. Mental elasticity was negatively correlated with occupational stress and depression (r=-0.559 and -0.559, both P<0.01) . Occupational stress and the two subscales mental stress reaction and physical stress reaction were positively correlated with depression (r=0.774, 0.734, and 0.725, all P<0.01) . After adjustment for confounding factors, occupational stress had a positive predictive effect on depression (β=0.744, P<0.01) , and mental elasticity had a negative predictive effect on depression (β=-0.221, P<0.01) . The analysis of mediating effect showed a significant direct effect of occupational stress on depression and a significant mediating effect of mental elasticity (a=-0.527, b=-0.227, c=0.744, c’=0.627; all P<0.01) , and the mediating effect of mental elasticity accounted for 16.08% of the total effect.@*Conclusion@#As a partial mediating variable, mental elasticity has an indirect effect on the relationship between occupational stress and depression and can alleviate the adverse effect of occupational stress and reduce the development of depression.

The changes of protein and lipid metabolism in patients with active inflammatory bowel disease / 中华消化杂志

Objective To compare the difference of protein and lipid metabolism between patients with inflammatory bowel disease and healthy controls,and to investigate the association of these changes with disease activity and location of the lessions.Methods The retrospective cohort study was carried out.The data of protein and lipid metabolisms collected from 195 patients with ulcerative colitis,76patients with Crohn's disease and 97 healthy controls during 1995 to 2007 were analyzed.Disease activity were evaluated using simple clinieal colitis activity index and simple index of Crohn's disease activity.The erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP)were measured.Results Serum levels of ESR in patients with ulcerative colitis were negatively linear correlated with serum levels of albumin/globulin ratio(β=-0.521,P＜0.01)and positively linear correlated with serum levels of α2globulin(β=0.319,P＜0.01).Serum levels of globulin in patients with Crohn's disease were positively linear correlated with serum levels of ESR(β=0.558,P＜0.01)and CRP(β=0.424,P=0.01).In ulcerative colitis,serum levels of albumin/globulin ratio,albumin and total cholesterol were significantly higher in patients with proctosigmoiditis than those in patients with lesions at other locus(P=0.003,0.005,0.038,respectively).In Crohn's disease,serum level of globulin was significantly higher in patients with lesions only at colon than that in patients with lesions only at small bowel(P=0.029).Conclusions Serum levels of albumin/globulin ratio and α2-globulin can be predictors of inflammatory activity in patients with ulcerative colitis.The increasing serum globulin may predict the progression of disease activity in patients with Crohn's disease.The nutritional deficiency is more critical in patiens with small bowel involvement than those with colon involvement.