Objective To examine the induction effects of bone marrow mesenchymal stem cells(BMSCs) transfected with bone morphogenetic protein 7 (BMP7) gene differentiating into chondrocytes. Methods We observed the phenotype of cells which were stained with alcian blue and HE climbing to the six pore plate with invert microscope. The glycosaminoglycan (GAG) value in culture medium was detected in control group,BMP7 transfect and culture medium induced groups after 7,14 and 21 days using standard curve method. Standard curve was described using galacturonic-acid as reference substance. The content of collagen Ⅱ was detected by ELISA method. Results HE and Alcian blue staining showed that BMP7 gene transfection group and the group induced by fluid possess the characteristics of chondrocyte. BMP7 induced BMSCs differentiation to chondrocyte which secrete specific protein called collagen Ⅱ and GAG. Content of GAG were (17.1±3.4),(39.5±5.4),(40.8±6.1)mg/L in control group,BMP7 gene transfected group and induced group,collagen Ⅱ were (89.7±14.3),(152.8±14.5),(155.5± 19.3)μg/L in these three groups separately. Comparing with control group,GAG and collagen Ⅱ of BMP7 gene transfected group and culture medium induced group increased obviously(all P < 0.05),but there was no significant difference between BMP7 gene transfeeted group and culture medium induced group (P > 0.05). Conclusion This active protein induces BMSCs differentiating into chondrocyte,in a level similar to that of inducing medium.

A series of novel sorafenib analogues were designed and synthesized. The cytotoxic activities of these compounds were tested in four tumor cell lines. Some of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 4-20 micromol x L(-1). Some compounds demonstrated competitive antiproliferative activities to sorafenib against tested cancer cell lines. Among them, compound 7c demonstrated significant inhibitory activities on ACHN, HCT116 and MDA-MB-231 cell lines with IC50 values of 9.01, 4.97, 6.61 micromol x L(-1), respectively.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Niacinamide ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Phenylurea Compounds ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Animals ; Apoptosis ; Aurora Kinase A ; antagonists & inhibitors ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Colonic Neoplasms ; pathology ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Xenograft Model Antitumor Assays

This study assessed the clinical application of transvaginal three-dimensional ultrasound (3D TVUS) in the diagnosis of congenital uterine malformation. A retrospective study was performed on 62 patients with congenital uterine malformation confirmed hysteroscopically and/or laparoscopically. The patients were subjected to transvaginal two-dimensional ultrasound (2D TVUS) and 3D TVUS. The accuracy rate was compared between the two methods. The accuracy rate of 3D TVUS was (98.38%, 61/62), higher than that of 2D TVUS (80.65%, 50/62). 3D TVUS coronal plane imaging could demonstrate the internal shape of the endometrial cavity and the external contour of the uterine fundus. It allowed accurate measurement on the coronary plane, and could three-dimensionally show the image of cervical tube, thereby providing information for the diagnosis of some complex uterine malformation. 3D TVUS imaging can obtain comprehensive information of the uterus malformation, and it is superior to 2D TVUS for the diagnosis of congenital uterine malformations, especially complex uterine anomaly.

Objective To evaluate the expression of RAR-? gene in cervical carcinoma cell lines SiHa,HeLa,C33A and Caski and to analyze the relation between their gene expression and the promoter methylation of RAR-? DNA.Methods The expression of mRNA and protein of RAR-? gene in the four cell lines were analyzed by RT-PCR,western blot and immunofluoreseence,respectively.Methylation specific PCR(MSP)was used to check whether there was methylation in the promoter of RAR-? gene.The demethylating agent 5-aza-2'-deoxycytidine(5-Aza-cdR)was used to treat methylated cell lines and the change of RAR-? gene methylation and RAR-? gene expression defects were observed.The cell proliferation was assayed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Results The mRNA and protein expression levels of RAR-? in cell lines SiHa,HeLa,Caski and C33A were 0.25 ?0.08,0,0.60?0.19,3.12?0.92 and 0.23?0.07,0,0.14?0.05,0.68?0.21,respectively.The mRNA and protein expression of RAR-? in SiHa,HeLa and Caski cell lines were decreased or silenced, whereas its expression increased in C33A cell line.MSP method showed that there were RAR-? gene methylation in SiHa,HeLa and Caski cell lines,while there was no RAR-? gene methylation in C33A cell line.After treated with 5-Aza-cdR,the mRNA and protein expression levels of RAR-? in SiHa,HeLa, Caski and C33A cell lines were 1.82?0.59,2.13?0.62,1.67?0.43,2.95?0.89 and 0.69?0.21, 0.83?0.29,0.56?0.16,0.64?0.20 respectively.The mRNA and protein levels of RAR-? had a significant difference between before and after interference with 5-Aza-cdR in SiHa,Helm,and Caski cell lines(P0.05).The 5-Aza-cdR treatment could suppress cell proliferation.Conclusions The RAR-? gene expression defects play an important role in the carcinogenesis of cervical cancer.Aberrant methylation in promotor region of RAR-? gene may be an important mechanism for the loss of expression of RAR-? gene.

Permeability is a key factor in the bioavailability of oral drugs. Therefore, in the early stage of drug discovery, accurate and efficient evaluation of drug permeability is essential. The parallel artificial membrane permeability assay (PAMPA) with Caco-2 cells model was used by the industry as early evaluation methods. At present, the Ussing chamber rat model is also widely used. This review summarizes the human data for the in vivo single-pass perfusion technique (Loc-I-Gut) – the gold standard, and then focuses on the basic principles, experimental operation, and efficiency of the three in vitro methods, with correlation to the effective permeability coefficient (P_eff) and fractional absorbed (Fa) in man. We provide recommendations for the use of proper permeability methods at different stages in drug discovery and development.

ObjectiveTo investigate the effects of fluid percussion injury(FPI) on survival and differentiation of transplanted human embryonic neural stem cells (HNSCs) in rats. MethodsThe HNSCs were separated from the cerebral cortex of the 8-week-old fetal and were cultured in DMEM/F12 combinated with EGF, bFGF and LIF. The rat models of FPI were made with fluid percussion system. The HNSCs labeled with BrdU were transplanted into the injured zone 24 hours after brain injury, then the rats were killed at the 1st and 4th week post-transplanted stages, and the brain slices were stained with immunocytochemistry. The GFAP, MAP-2, and BrdU positive cells were investigated.ResultsThe transplanted HNSCs migrated to the whole brain, and differentiated into GFAP and MAP-2 positive cells. MAP-2 positive cells were observed at 1 week post-transplanted stage, on the contrary, more GFAP positive cells were discovered 4 weeks after transplantation. Part of the HNSCs migrated to the choroids plexus of the lateral ventricle and microvessels. ConclusionThe transplanted HNSCs survive in the injured zone, and differentiate into astrocytes gradually during the recovery. The host devours part of the HNSCs.

Curcumin has been reported to possess antitumor activity with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. In order to overcome these limitations and discover novel small molecules with potential antitumor activity, 29 curcumin mimics were synthesized, which were confirmed by 1H NMR and HR-MS, and their cytotoxic property was evaluated against five human cancer cell lines in vitro. Compounds 16, 18 and 19 exhibited good cytotoxic property, their IC50 value were even below 5 micromol x L(-1) to some cancer cell lines, 5-9 times better than curcumin.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Curcumin ; analogs & derivatives ; chemical synthesis ; pharmacology ; Drug Screening Assays, Antitumor ; Humans ; Inhibitory Concentration 50

OBJECTIVETo establish an experimental animal model of Alzheimer's disease (AD) with clinical and pathological specificity conformed to AD in human, and to observe the effect of Zhinao Capsule (ZNC) on learning, memory and patho-morphological parameters in the model.

METHODSThe experimental AD model of rats was improved and established by combined injection of beta-amyloid protein (beta-AP) to lateral ventricle and transforming growth factor beta 1 (TGF beta 1) to brain. The learning and memory function of the model rats were tested by step-through test and water-maze test, and the number and cross area of beta-AP deposited macula in cerebral cortex and CA1 region of hippocampus were estimated quantitatively using immunohistochemical method and image pattern analysis.

RESULTSThe improved AD animal model showed both the specificity of behavior (learning and memory impairments) and the typical pathological specificity (beta-AP deposited macula). ZNC could effectively improve the impairment of learning and memory and reduce the number and cross area of beta-AP deposited macula in cerebral cortex and hippocampus CA1 region in the AD model rats.

CONCLUSIONThe AD rat model induced by the combined injection of beta-AP and TGF beta 1 is a good animal model simulated to the clinical reality, which could be used to screen and evaluate the anti-dementia agents. ZNC could display anti-dementia effect of the AD model rats.

Alzheimer Disease ; drug therapy ; physiopathology ; Amyloid beta-Peptides ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Learning ; Male ; Memory ; drug effects ; Random Allocation ; Rats ; Rats, Wistar ; Transforming Growth Factor beta

Adolescent ; Blood Vessel Prosthesis Implantation ; Child ; Child, Preschool ; Ductus Arteriosus, Patent ; therapy ; Equipment and Supplies ; Female ; Humans ; Infant ; Male ; Video Recording