Objective: To study the relationship between FAT10 expression and biological behaviors in inif trating ductal carcinoma of breast. Methods: The expressions of diubiquitin (FAT10), estrogen receptor (ER), progesterone receptor (PR) and c-erbB2 in 50 cases of inif trating ductal carcinoma of breast were detected by immunohistochemistry. Western blot was used to detect FAT10 expression in MB-MDA-435, MB-MDA-435-transfected with FAT10 siRNA expression plasmid, MCF-7 and MCF-7-transfected with FAT10 expression plasmid, respectively. Transwell was used to detect invasion capability of MB-MDA-435, MB-MDA-435-transfected with FAT10 siRNA expression plasmid, MCF-7 and MCF-7-transfected with FAT10 expression plasmid. Results: hTe expression intensity of FAT10 was signiifcantly correlated to patho-grading, lymph nodes metastasis, distant metastasis and TNM staging (P<0.01), but not to age of patients and tumor sizes in iniftrating ductal carcinoma of breast (P>0.05). hTe expression intensity of FAT10 in receptor- negative group was obviously stronger than that in receptor- positive group (P<0.01). hTe expression intensity of FAT10 in triple-negative breast cancer was signiifcantly stronger than that in non- triple-negative breast cancer (P<0.01). hTe survival rate of patients with FAT10 positive expression was significantly lower than negative ones (P<0.05). Western blot results showed that FAT10 intensity in MB-MDA-435 significantly higher than that in MCF-7. Up-regulation expression of FAT10 could obviously increase the invasion capability of MCF-7, and down-regulation of FAT10 could signiifcantly decrease the invasion capability of MB-MDA-435 (P<0.01). Conclusion: FAT10 might increase the invasion capability of breast cancer cells by direct or indirect ways, and play an important role in invasion and metastasis of breast cancer. FAT10 might be an independent index for evaluation of breast cancer prognosis, and a potential target for breast cancer therapy, especially for triple-negative breast cancer.

Objective To investigate the hepatocyte targeted specific property of galactosylated chitosan-graft-polyethyleneimine (GC-PEI)/DNA complexes in vitro and in vivo.Methods With the plasmid expressing enhanced green fluorescent protein (pEGFP-C1) as the reporter gene,the formation of GC-PEI/DNA complexes was induced to self-assemble in 0.01 mol/L phosphate buffered saline(PBS),150 mmol/L NaCl,or 5% glucose solution (GS).The complexes were characterized by the particle size,Zeta potential,DNA binding and protection capacity,and further tested for cytotoxicity and hepatocyte targeted degradation of DNaseⅠand the serum,which presented as a well-formed sphere or compacted nucleocapsid structure at a diameter of 50-200 nm.The GC-PEI copolymer showed no obvious toxicity in the tested cell lines.Acute toxicity assay revealed that the mice grew well in 2 weeks with GC-PEI dosage from 50 to 300 μg.The assay by flow cytometry and fluorescent microscope showed that the transfection efficiency in hepatocyte lines (L02,QSG7701/core) was higher than that in non-hepatocyte lines (SGC7901,HBE) in vitro.In vivo,the GFP was obviously expressed in the liver tissue and not expressed in other organs 48 h after the transfection.Conclusion GC-PEI copolymer may carry the exogenous gene specifically to hepatocytes in vitro and in vivo,which has very good liver targeted specific property.

Objective With a network meta-analysis,to compare the effects and safety of seven clinically common-used induction methods.Methods Publications of randomized controlled trials between January 1,1980 and November 20,2011 were searched on Medline,Embase and Cochrane Central Register of Controlled Trials with the following terms including dinoprostone,misoprostol,Foley catheter,oxytocin and labor induction.A network meta analysis with both direct and indirect comparison was applied for 48 randomized controlled trials (19 819 participants) recruited,and the following seven induction methods applied in the publications were compared:oxytocin (intravenous,Ⅳ),vaginal dinoprostone,intracervical dinoprostone,oral misoprostol,vaginal misoprostol,sublingual misoprostol and foley catheter.The main outcomes were the proportion of vaginal delivery within 24 hours,cesarean section rate,uterine hyperstimulation rate and Apgar score＜7 at 5 min after birth.Medline,Embase and Cochrane Central Register of Controlled Trials were searched between January 1,1980 and November 20,2011.Results Foley catheter methods had the lowest cesarean section rate and the lowest uterine hyperstimulation rate.Vaginal misoprostol method had the highest number of vaginal delivery within 24 hours,but the highest uterine hyperstimulation rate.The lowest rate of neonatal Apgar score＜7 at 5 min was found in women using sublingual misoprostol,while the highest in those using vaginal Dinoprostone.Oxytocin (Ⅳ) method had the lowest number of vaginal delivery within 24 hours and the highest cesarean section rate.Conclusion Foley catheter method is the best available option for labor induction in terms of efficacy and safety,while the induction effect of oxytocin (Ⅳ) was not good enough.Vaginal misoprostol and vaginal dinoprostone methods had relative good induction effect but with obvious adverse effects.

Objective To evaluate the relationship between positive thyroid autoantibody and risk of preterm birth.Methods Literature search was done in PubMed,Embase,China Academic Journal Network Publishing Database,Wanfang Medical Database and China Biology Medicine disc databases from January 1st,1989 to January 26th,2012.Criteria for inclusion included:(1) Prospective cohort study; (2) The exposure was positive thyroid autoantibody and outcome was preterm birth; (3) The enrolled subjects were pregnant women without cardiovascular or rheumatic disease; (4) Relative risk (RR) and its 95％ confidence interval (95％CI) of preterm birth were provided in the study.Meta-analysis was performed by Stata 12.0.The relationship between positive thyroid autoantibody and risk of preterm birth was evaluated by RR and 95％ CI.Results Ten cohort studies were enrolled.One thousand six hundred and fifty seven cases of preterm birth occurred among 25 081 pregnant women.Heterogeneity among the 10 studies was found in meta-analysis (I2 =79.2％,P＜0.01).The risk of preterm birth in pregnant women with positive thyroid autoantibody was higher than those in control group by random effects analysis (RR=1.61,95％CI:1.18-2.20,P＜0.05).Subgroup analysis was further performed.In five studies,the cases of control group were pregnant women with normal thyroid function; heterogeneity was not found in these five studies (I2=39.1％,P=0.160); and RR of the risk of preterm birth was 2.55 in pregnant women with positive thyroid autoantibody (95 ％ CI:2.04 3.19,P＜0.01).In the other five studies,the cases of controlgroup were pregnant women who had not been ruled out the possibility of thyroid dysfunction;heterogeneity was not found in these five studies either (I2 =0.0％,P =0.970); and RR was 1.18(95 ％ CI:1.01-1.37,P＜0.05).After excluding two low-quality studies,RR of the risk of preterm birth was 1.72 in pregnant women with positive thyroid autoantibody (95％CI:1.18 2.53,P＜0.05).The funnel plots presented symmetrical graphics,indicating that there was no publication bias.Conclusions Positive thyroid autoantibody in pregnant women is a risk factor of preterm birth.

[ABSTRACT]AIM:ToinvestigatetheeffectofmiR-155-specificsiRNAaloneorincombinationwithcytosinear-abinoside (Ara-C) on the growth and apoptosis of Burkitt lymphoma Raji cells .METHODS: miR-155-specific siRNA and/or Ara-C were used to treat the cells .Quantitative real-time polymerase chain reaction was used to detect the expres-sion of miR-155.The growth of the cells was analyzed by CKK-8 assay.The cell apoptosis was determined by flow cytome-try.RESULTS:The miR-155 expression level of the cells transfected with miR-155 siRNA was significantly lower than that in the 2 control groups .Ara-C or miR-155 siRNA alone inhibited the growth of Raji cells in a dose-depend manner . miR-155 siRNA combined with Ara-C produced more inhibition of cell proliferation (P<0.05).After treatment for 48 h, the apoptotic rate of Raji cells in miR-155 siRNA+Ara-C group [(38.4 ±1.4)%] was higher than that in Ara-C group [(16.5 ±0.3)%] and miR-155 siRNA group [(14.6 ±0.3)%], with statistically significant difference (P<0.05). The expression of caspase-3 in Ara-C+miR-155 siRNA group was increased significantly as compared with Ara-C group and miR-155 siRNA group.CONCLUSION:miR-155-specific siRNA enhances the chemosensitivity of Raji cells to Ara-C by inducing apoptosis through the caspase-3 pathway .

Objective To investigate the therapeutic effects of thymopentin(TP-5)for the experimentsl autoimmune encephalomyelitis(EAE)in rats.Metbods The EAE model wss established in wistar rats immunized with fresh guinea pig spinal cord homogenate(GPSCH)and complete Freund's adjuvant (CFA).Wistar rats were divided randomly into five groups:normal control group,EAE group,dexamethaSone(DXM)group,low dose TP-5 treated group,hish dose TP-5 treated group.The levels of IL-12 and IL-10 in serum of wistar rats were detected by sandwich-ELISA on day 7,14 and 21 post immunization.Resuits Morbidity and clinical score of low dose TP-5 treated group and DXM group were significantly lower than those of EAE group and hish dose TP-5 treated group(P＜0.01).Morbidity and clinical score of DXM group were significantly lower than those of low dose of TP-5 treated group(P＜0.01).The levels of IL-12 of EAE group,DXM group,low dose TP-5 treated group and high dose TP-5 treated group were significantly higher than of normal control group at each time point(P＜0.01).The levels of IL-12 of DXM group and low dose TP-5 treated group were significantly lower than that of EAE group(P＜0.01),meanwhile the levels of IL-10 of DXM group and low dose TP-5 treated group were significantly higher than that of the rest groups on day 14 and 21 post immunization(P＜0.01).Conclusion TP-5 has protective effects on EAE,and its functional mechanism may be associated with down.regulation of IL-12 as well as up-regulation of IL-10,so as to reverse the imbalance of TH1/TH2 responses by bidirectional regulation.

Carotid Body Tumor ; surgery ; Humans ; Hypertension ; Pressoreceptors

OBJECTIVETo observe the effects of high expression of recombinant trichosanthin (rTCS) on the cell proliferation and cell cycle of human cervical cancer Caski cells.

METHODEukaryotic expression plasmid pcDNA3.1(-)/6His-TCS was constracted and stably transfected into Caski cells. RT-PCR,Western-blot were used to select the clones with rTCS high-expressing. Using pcDNA3.1(-)-transfected cells as the control, MTT assay and flowcytometry were used to elucidate the effects of rTCS high expression on cell growth and cycle regulation in Caski cells.

RESULTThe Caski cells with stable high expression of rTCS was successfully established, which could inhibit the cell growth (P<0.01) and arrest Caski cells in G1 and G2 phases (P<0.05) obviously.

CONCLUSIONHigh expression of rTCS can inhibit the growth of Caski cervical cancer cells, which might provide a new pathway for the therapy of cervical cancer.

Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Humans ; Recombinant Proteins ; pharmacology ; Transfection ; methods ; Trichosanthin ; pharmacology ; Uterine Cervical Neoplasms ; pathology

OBJECTIVE：To investigate the inhibitory effects of total alkaloids of Gelsemium elegans （TAG） on the proliferation and angiogenesis of human colon cancer cells. METHODS ：Human colon cancer cell line HT- 29 and HUVEC were cultured in vitro . After the intervention of low- ，medium-，high-dose TAG （40，80，120 μg/mL），the morphology of the two cells was observed by fluorescence inversion microscope. The survival rate of HT- 29 cells and HUVEC was detected by CCK- 8 assay. Flow cytometry was used to detect HT- 29 cell cycle. The migration rate ，invasion rate and tube number of HUVEC were observed by scratching test ，Transwell invasion experiment and tube formation experiment. RESULTS ：Compared with blank group ，HT-29 cells and HUVEC were decreased to different extents in TAG groups ；dead cells were observed ，and the survival rate of both decreased significantly （P＜0.05 or P＜0.01）. The proportion of HT- 29 cells at G 2/M phase in TAG groups as well as those at G 0/G1 phase in medium-dose group were increased significantly ；the proportion of HT- 29 cells at S phase in TAG groups as well as those at G 0/G1 phase in high-dose group were decreased significantly （P＜0.05 or P＜0.01）. Survival rate ，migration rate and invasion rate of HUVEC were decreased significantly in TAG groups ，and tube number was also decreased significantly at each time point during 4-24 h（P＜0.01）. CONCLUSIONS ：TAG have inhibitory effect on the proliferation of human colon cancer HT- 29 cells and HUVEC，can change HT- 29 cell cycle ，inhibit the migration ，invasion and tube formation of HUVEC.

Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal cells in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.
Adaptor Proteins, Signal Transducing ; chemistry ; metabolism ; Animals ; HEK293 Cells ; Heat-Shock Proteins ; chemistry ; metabolism ; Humans ; Lysine ; metabolism ; Mice ; Neurons ; metabolism ; pathology ; Oxidopamine ; pharmacology ; Parkinson Disease ; metabolism ; pathology ; Proteasome Endopeptidase Complex ; metabolism ; Protein Stability ; Proteolysis ; drug effects ; Sequestosome-1 Protein ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination ; drug effects