RESUMO
Objective To investigate the effects of Xiaoyao Kang'ai Jieyu Formula on mice with breast cancer related depression; To explore its mechanism. Methods BALB/c female mice were set as study objects. Subaxillary injection of inflammatory 4T1 cells and intraperitoneal injection of corticosterone were used to establish a model of breast cancer related depression. According to the consumption of sugar water, mice were randomly divided into blank group, model group, paclitaxel group, Xiaoyao Kang'ai Jieyu Formula group, chemotherapy+fluoxetine group, and chemotherapy + Xiaoyao Kang'ai Jieyu Formula group. After 21 days, sucrose preference test, open-field test, and novelty feeding test were performed to detect changes in the behavior of mice in each group. ELISA were used to detected the contents of corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in plasma, and the contents of 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), tumor markers carbohydrate antigen CA153, CA125 and carcinoembryonic antigen (CEA) in serum. Results Compared with the blank group, the consumption of sugar, horizontal and vertical movements of mice in the model group significantly decreased (P<0.01, P<0.05); the latency of ingestion significantly increased (P<0.01, P<0.05); the levels of tumor markers CA153, CA125, CEA and some indexes of HPA axis significantly increased (P<0.01); the expressions of monoamine neurotransmitter NE, DA and 5-HT significantly decreased (P<0.01). Compared with the model group, sugar consumption and autonomic activity significantly increased in the chemotherapy + Xiaoyao Kang'ai Jieyu Formula group, and behavioral despair condition was improved (P<0.01, P<0.05); the content of tumor markers and some indexes related to HPA axis significantly decreased (P<0.01, P<0.05); the contents of 5-HT, DA and NE significantly increased (P<0.01, P<0.05). Conclusion The combination of Xiaoyao Kang'ai Jieyu Formula and paclitaxel can effectively relieve the depressive symptoms of breast cancer related depression.
RESUMO
Two new MAR segments (M14 and M17) were cloned from tobacco genome. Both of the sequences contained several typical consensus sequences of MARs, which were different from the original MAR sequence, such as 90%AT-box, A-box, T-box, the base unpairing regions (BUR), autonomously replicating sequences (ARS), the consensus sequence for topoisomerase II, MAR recognition sequence (MRS), origin of replication (ORI), curved DNA motifs and ATATTT et al. To investigate the effects of these two sequences on gene expression in transgenic plants, 3 plant expression vectors were constructed with uidA gene coding beta-glucuronidase (GUS) which were flanked on one side and on both sides by the MARs we obtained. These plant expression vectors with one or two MARs were transformed into tobaccos via Agrobacterium-mediated transformation method, with the plant expression vector pCAMBIA2301 without MAR and wild type tobacco as controls. GUS histochemical staining results showed that the uidA gene expressed stably in transgenic tobaccos. Quantitative detection of GUS activity showed that the MARs could increase GUS expression levels in vivo in contrast to the controls, wherever they were flanked on one side or both sides of uidA gene. The vector ligated with MARs in the same direction on both sides of uidA could increase the GUS expression level much better than both vectors which just ligated with single MARs on one side. The former one increased the average GUS activity for 3.14 folds, but 1.56 and 2.43 folds for the latter two vectors with single MARs respectively contrasting to the pCAMBIA2301 control. But the expression differences among individual transformants were still obvious. Therefore, it was concluded that the DNA sequences we obtained in this experiment were two novel MARs and could enhance gene expression in vivo. In the meanwhile, although the numbers of the MARs typical motifs in M14 were more than in M17, especially the 90% AT box which had been considered to be the highest correlative motif with binding strength in vitro, the enhancement of gene expression was lower yet, which implied no correlation between improvement of gene expression and binding strength between MARs and nuclear matrix in vitro.