OBJECTIVE: The pH-sensitive procationic liposomes were prepared, with hydroxycamptothecin (HCPT) as model drug. METHODS: The cationic liposomes were prepared by film dispersion method. The encapsulation efficiency was determined after removing unentrapped HCPT by Sephadex-G50 chromatographic column. Carboxymethyl chitosan was used to coat the cationic liposomes, then the liposomes were extruded through high pressure homogenizer. Zetasizer was used to determine the zeta potential, average size of the HCPT liposomes. pH sensitivity analysis was made through experiments of red blood cell hemolysis and tumor distribution is analysised. RESULTS: The size of liposomes was around 96 nm and drug encapsulation efficiency was 78.5%. The membrane fusion of red blood cells with procationic liposomes was significantly different between pH 6.5 and pH 7.4 and the in vivo experiments in tumor-bearing mice suggested that they had a high tumor distribution. CONCLUSION: The pH-sensitive procationic nanoliposomes were easy to prepare and were expected to be a promising anti-tumor drug delivery system. Copyright 2012 by the Chinese Pharmaceutical Association.

DNA, Neoplasm ; analysis ; Female ; Flow Cytometry ; Humans ; Hydatidiform Mole ; diagnosis ; genetics ; In Situ Hybridization, Fluorescence ; Microsatellite Repeats ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Pregnancy ; Triploidy ; Uterine Neoplasms ; diagnosis ; genetics

Humans ; Microbial Sensitivity Tests ; Pneumoconiosis ; diagnosis ; microbiology ; Sputum ; microbiology

Objective To explore the effects of advanced glyeosylation end products (AGEs) on the binding of hepatic nuclear factors to the human insulin receptor (hlR) gene promoter. Methods The oligonueleotides with hlR gene promoter activity, 42 bp (spanning -1 441 to -1 400, US1) or 146 bp (spanning -638 to -493), were artificially synthesized, with point mutations at 5 key G residues in 42 bp US1 m5 oligonucleotides. US1 and rat hepatic nuclear extracts (HNE) were incubated with glucose 6-phosphate, prior to non-competition and competition gel retardation electrophoresis. Results Competition gel retardation electrophoresis showed that the binding capacity of 32p-labeled US1 probe to HNE could be signifficantly decreased with increased US1. US1-AGEs and US1m5 decreased the binding of probe to HNE as well, but only partly affected the electrophoretie bands [1,5,10 ng US1-AGEs: (41.08±2.86)%, (27.64±2.92)%, (15.35±1.81%) vs (52.05±1.79)%]; 5,10 ng US1m5: (5.20± 1.03)%, (1.81±0.21)% vs (52.05±1.79)%]. AGEs formed on HNE could increase the binding of HNE to probe, along with nonspecifie binding increasing. Conclusion The impact of AGEs on hlR gene expression seems to be related to the effects on cis-elements and trans-acting factors.

Adult ; Aged ; Erythrocyte Indices ; Hemorheology ; Humans ; Male ; Middle Aged ; Silicosis ; blood

To review recent studies on the research advance of RET( Rearranged during transfection) on-cogene in thyroid cancer,breast cancer,and lung cancer.The literatures on the structure of RET gene and coding product,cell signal transduction,relationship among thyroid cancer,breast cancer,and lung cancer are reviewed. RET gene encoding tyrosine kinase receptor,involving in cell signal transduction,rearrangement of RET gene is frequently seen in thyroid cancer,which is reported more and more in breast cancer,and lung cancer.Rearrange-ment of RET gene is closely correlated with the occurrence and progress of thyroid cancer,breast cancer,and lung cancer.Taking together,these findings suggest that RET present an attractive therapeutic target for the treatment of certain cancer subsets.

OBJECTIVETo investigate the effect of midazolam on human ether-a-go-go (hERG) K+ channels exogenously expressed in human embryonic kidney cells (HEK-293) and the underlying molecular mechanisms.

METHODSWhole-cell patch clamp technique was used to record WT, Y652A and F656C hERG K+ current expressed in HEK-293 cells.

RESULTSMidazolam inhibited hERG K+ current in a concentration-dependent manner, the half-maximum block concentrations (IC50) values were (1.31 ± 0.32) µmol/L. The half-activation voltage (V1/2) were (2.32 ± 0.38) mV for the control and (-1.96 ± 0.83) mV for 1.0 µmol/L midazolam. The half-inactivation voltage (V1/2) was slightly shifted towards negative voltages from (-49.25 ± 0.69) mV in control to (-57.53 ± 0.53) mV after 1.0 µmol/L midazolam (P < 0.05). Mutations in drug-binding sites (Y652A or F656C) of the hERG channel significantly attenuated the hERG current blockade by midazolam.

CONCLUSIONMidazolam can block hERG K+ channel and cause the speed of inactivation faster. Mutations in the drug-binding sites (Y652 or F656) of the hERG channel were found to attenuate hERG current blockage by midazolam.

Dose-Response Relationship, Drug ; Ether-A-Go-Go Potassium Channels ; drug effects ; HEK293 Cells ; Humans ; Midazolam ; pharmacology ; Mutation ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology

Adolescent ; Brain Neoplasms ; diagnosis ; Child ; Child, Preschool ; Endocrine System Diseases ; etiology ; Female ; Follicle Stimulating Hormone ; blood ; Humans ; Infant ; Luteinizing Hormone ; blood ; Magnetic Resonance Imaging ; Male ; Tomography, X-Ray Computed

Objective To explore the efficacy and safety of metformin therapy on obese nondiabetic children with hyperinsulinemia.Methods Twenty-two obese nondiabetic children with hyperinsulinemia were divided into two groups:control group(dietary counseling and exercise) and treatment group(dietary counseling and exercise combined with metformin).The changes of body mass index(BMI),fasting glucose(FPG),fasting insulin(FINS),insulin resistance(HOMA-IR),2 h PG,2 h INS,total cholesterol(TC) and triglyceride(TG),before and after treatment were determined,and the findings were compared and analyzed.Results After treatment,there were significant differences in BMI,TC,FINS,HOMA-IR levels(P0.05),except the BMI(P

AIM:To research the effects of Kanglaite(KLT)injection on antitumor and expression of epidermal growth factor receptor(EGFR)in Lewis lung carcinoma(LLC).METHODS:A total of 40 C57BL/6 mice were randomly divided into four groups,including model group,KLT 6.25,12.5,25 mL/kg groups.All the mice were injected with 2?106 LLC cells at 1st day.At the next day,mice in the KLT groups were peritoneally injected with KLT for 14 days.And at the 16th day,all the mice were sacrificed and the tumors were harvested.The tumor weight was measured and the tumor growth inhibition rate was analyzed.The expression of EGFR was detected by westernblot.RESULTS:The growth of LLC was significantly inhibited by KLT,the changes of tumor appearance and histology were affected and the expression level of EGFR was decreased.CONCLUSION:KLT injection could obviously inhibit the growth of LLC,whose mechanism maybe related to the inhibition of EGFR expression.