Objective: To investigate the effect of berbamine (BBM) on the induction of apoptosis in human lung cancer cell A549 cells and the activity of TNF-α-JNK signaling pathway. Methods: After the A549 cells being treated with BBM at different concentration, the inhibitory effect of BBM on proliferation was detected by MTT assay. Cell morphological changes were detected by light microscope. Alteration of apoptosis rate of A549 cells was determined by Annexin V/PI double staining. Western blotting was used to detect the activity of apoptosis-related proteins, including Bcl-x, Caspase-3, and PAPR. The expressions of c-jun N-terminal kinase (JNK) and p-JNK were determined by Western blotting. Changes of tumor necrosis factor-alpha (TNF-α) were detected by fluorescent quantitative PCR and ELISA, respectively. Finally, the impacts of BBM on the proliferation and apoptosis of A549 cells were detected in the absence or presence of a JNK inhibitor. Results: BBM significantly inhibited the growth of A549 cells in a dose-dependent manner. The IC50 of 24 h was 9.01 μmol/L. Cells treated with BBM showed the typically morphological characteristics of apoptotic cells. Annexin V/PI double staining test indicated that BBM could induce the apoptosis of A549 cells in a dose-dependent manner. The early apoptotic population of cells treated with 10 μmol/L BBM was 13.8%, which was 5.6 times higher than that of the control. BBM decreased the expression of anti-apoptotic protein Bcl-x and increased the activity of proapoptotic proteins of caspase-3 and PARP. The mRNA and the protein expression levels of TNF-α were significantly increased by BBM treatment. The p-JNK expression was also dramatically up-regulated after BBM treatment. The effects of BBM on the proliferation and apoptosis in A549 cells were significantly reduced when JNK pathway was blocked. Conclusion: BBM could inhibit the growth and induce the apoptosis of A549 cells, and its mechanism may be related to the activated TNF-α-JNK signaling pathway.

Azabicyclo Compounds ; blood ; Chromatography, Gas ; Humans ; Piperazines ; blood ; Serum ; chemistry

Asphyxia Neonatorum ; blood ; drug therapy ; Creatine Kinase, MB Form ; blood ; Female ; Humans ; Infant, Newborn ; Male ; Naltrexone ; analogs & derivatives ; therapeutic use ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood

AIM: To explore the effect of lacrimal duct laser with lacrimal drainage tubes and stents implantation for complexity dacryagogatresia.
METHODS: There were 65 patients ( 82 eyes ) with compound tears nasolacrimal duct obstruction who received lacrimal drainage tubes and stents implantation after laser. The lacrimal duct stents were removed through nasal cavity after 1mo. Lacrimal drainage tubes were removed after 3-6mo. Follow-up periods were 6mo to 1a.
RESULTS: In the 65 patients (82 eyes), 71 eyes were cured, 5 eyes improved, the efficient rate was 93%; there were 6 eyes (7%) with epiphora.
CONCLUSION: Lacrimal duct laser with lacrimal drainage tubes and stents implantation was efficient for complexity dacryagogatresia.

AIM To establish the expermental model in vitro for the study of mechanism of antitumor drug resistance and the screening of antitumor drug. METHODS By continuously exposing cells to gradually increasing concentration of drug and agar cell colony forming technique, using dye exclusive method for determing cytotoxic effect, a murine leukemia L1210 cell subline were established,which exhibited 40 fold resistance to Cis diamminedichloro platinum(DDP). RESULTS The doubling times, plate efficiency, cell cycle, DNA index and cell morphology of DDP resistant L1210 subline were similarto those of its parant cell line. When the cell subline was stored with DDP at -196℃ for 6 months and then was recovered, its characterization of antitumor drug resistance was still maintained to a period of 5 months without DDP. DDP resistant L1210 subline was characterized with cross resistance to Carboplatin, Mitomycin, Thio Tepa, Methotrexate, Vincristin and Mustine Hydrochloride, but with no cross resistance to Harringtonine and Adriamycin. It was seemed more sensitive to Cytarabine and Fluorouracil. CONCLUSION DDP resistant L1210 subline is a good experimental model in vitro for the study of mechanism of antitumor drug resistance and the screening of antitumor drug.

Objective To investigate the mechanism of presynaptic protein (Munc18) antibody in inducing epilepsy on rat. Methods Munc18 antibody was continuously micro-injected into CA1 area of hippocampus in Sprague-Dawley (SD) rat (the injection times were nine). The potential epileptic seizure was evaluated according to both electroencephalogram (EEG) and behaviors. HE, Nissle and TUNEL staining were applied on rat brain sections as to detecting the cell damage and apoptosis after tenth week. Results Ten of twelve rats produced epileptic EEG, five cases among these ten rats maintained abnormal EEG after the sixth week since injections. Nine of the above twelve rats had epileptic seizure according to Racine grade one to four, four cases among these nine rats kept seizure after the sixth week since injections. The number of neurons decreased (155?20,P

Objective To elucidate the influence of fetal genotype in both non-diabetic gravidas and pregnant women on gestational diabetes mellitus (GDM) through analysis of the genotype discrepancy between maternal and fetal Pro12A1a single nucleotide polymorphism (SNP) of peroxisome proliferator-activated receptor gamma 2 (PPARG2) genes.Methods Pregnant women,who delivered in the Obstetrics and Gynecology Hospital of Fudan University from October 2005 to February 2007,and their newborn babies were selected,and were divided into GDM and control group.The GDM group consisted of 55 gravidas with GDM and 40 newborns born to the GDM mothers,and the control group consisted of 173 healthy gravidas and their 50 neonates.Polymerase chain reaction-denaturing high-performance liquid chromatography was applied to detect the distribution of PPARG2 Pro12Ala alleles in all subjects.The concentrations of plasma fasting blood sugar (FBS) and several bio-markers of lipids,including total cholesterol,triglyceride,apoprotein A,high-density lipoprotein and low-density lipoprotein,were also tested for the mothers.Results (1) No significant difference was found in the frequencies of Pro/Pro genotype between the GDM mothers and control mothers (94.6% vs 90.8%,P > 0.05),nor between the GDM offspring and control offspring (95.0% vs 94.0%,P >0.05) or between the GDM mothers and GDM offspring (P > 0.05).The same was shown in the frequencies of Pro/Ala genotype both between the GDM mothers and control mothers (5.5% vs 9.2%,P >0.05) and between the GDM offspring and control offspring (2.5% vs 3.0%,P > 0.05).(2) Within both GDM and control group,the maternal FBS and various lipids concentrations of Pro/ Pro genotype gravidas showed no significant difference compared to those of Pro/Ala genotype mothers (P > 0.05).(3) Based on the four possible PPARG2 genotype pairs between the mothers and fetuses,Pro/Pro mother and her Pro/Pro fetus,Pro/Ala mother and her Pro/Ala fetus,Pro/Ala mother and her Pro/Pro fetus,and Pro/Pro mother and her Pro/Ala fetus,less Pro/Pro pairs and more Pro/Ala pairs were found in the GDM group than in the control (72.5% vs 92.0%,P=0.014; 27.5% vs 6.0%,P< 0.05).Conclusions Neither the maternal nor the offspring's Pro/Ala genotypes is associated with the genesis of GDM.However,the discrepancy of PPARG2 Prol2Ala polymorphism between mother and her fetus implies a possible cause of GDM.

OBJECTIVETo apply needle-knife to treat lumber disc herniation (LDH) and surface electromyography were used to analyze biomechanical characteristic of patient's lumber muscle to make a comprehensive evaluation on its efficacy.

METHODSThirty patients who met the inclusive criteria were selected and treated with needle-knife, once a week for 2 weeks. Visual analogue scale (VAS), ASLR and JOA score before and after treatment were observed. Surface electromyography was applied to test the surface electromyography signals. AEMG, MFs and MPF were calculated before and after the treatment.

RESULTSAfter treatment, VAS was significantly reduced, ASLR, JOA, AEMG and MPF were obviously increased, and the absolute value of MFs was lowed (all P < 0.01).

CONCLUSIONThe needle-knife could significantly relieve lumbar muscle strength, muscle tone and muscle fatigue, improve in the imbalance of lumbar extensor muscle group, leading to the recovery of biomechanical characteristic, and the clinical efficacy is superior.

Acupuncture Therapy ; Adult ; Electromyography ; Female ; Humans ; Intervertebral Disc Displacement ; diagnosis ; physiopathology ; therapy ; Lumbar Vertebrae ; physiopathology ; Male ; Middle Aged

PEG-modified magnetic Fe3O4 (Fe3O4-PEG) nanoparticles were sythesized using a solvothermal reaction and characterized with transmission electron microscopy (TEM) and thermo gravimetric analysis (TGA). The photothermal effect and photothermal destruction of cancer cells were evaluated. Then the doxorubicin loaded Fe3O4-PEG (DOX-Fe3O4-PEG) nanoparticles were prepared. The cytotoxicity and combined chemotherapy/photothermal therapy (PTT) effect were investigated. Uniform PEG coated Fe3O4 nanoparticles with particle size of 155 nm were obtained in the experiment. The loading and release of doxorubicin on Fe3O4-PEG were pH-dependent. The drug loading capacity in water was 21%. The results of MTT indicated a good biocompatiblity of Fe3O4-PEG nanoparticles and high cytotoxicity of DOX-Fe3O4-PEG. In combined therapy experiment, photothermal therapy demonstrated unambiguously enhanced chemotherapy efficacy. In conclusion, the obtained Fe3O4-PEG nanoparticles which exhibit good photothermal effect and drug loading capacity can be used for chemotherapy and photothermal therapy. The synergetic anti-tumor activity indicates the potential for the combined application of chemotherapy and photothermal therapy in cancer treatment.
Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Survival ; drug effects ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Carriers ; Ferrosoferric Oxide ; chemistry ; Humans ; Hyperthermia, Induced ; MCF-7 Cells ; Magnetite Nanoparticles ; chemistry ; Particle Size ; Polyethylene Glycols ; chemistry

Cryptotanshinone (CPT), a lipid soluble active compound in Salvia miltiorrhiza, has a significant inhibitory effect on multiple malignant tumors, e. g. chronic myeloid leukemia (CML) cells and can effectively enhance imatinib's chemotherapeutic effect. However, its functional molecular mechanism remained unclear. In this experiment, the authors conducted a systematic study on the effect of CPT on the imatinib sensitivity and P-glycoprotein (P-gp) expression in CML cells by using CML cells K562 and imatinib persister K562-R. The MTT assays were performed to determine CPT's impact on the inhibitory effect of imatinib. Annexin V-FITC/PI staining analysis was used to detect the changes in the cell apoptosis rate. The active changes in apoptosis regulatory proteins Caspase-3, Caspase-9 and PARP were determined by Western blot. After the cells were pretreated with the gradient concentration of CPT, the expression of P-gp was analyzed by Western blot and flow cytometry. The changes in intracellular concentrations of imatinib were determined by HPLC analysis. The results indicated that the pretreatment with CPT significantly increased the proliferation inhibiting and apoptosis inducing effects of imatinib on K562 and K562-R cells as well as the degradation product expression of pro-apoptotic proteins Caspase-3, Caspase-9 and PARP, with a significant difference with the control group (P < 0.01). However, CPT showed no impact on the P-gp expression in CML cells and the intracellular concentrations of imatinib. In summary, the findings suggested that CPT enhanced the sensitivity of CML cells to imatinib. Its mechanism is not dependent on the inhibition in P-gp expression and the increase in intracellular drug concentration.
ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; genetics ; metabolism ; Caspase 9 ; genetics ; metabolism ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Imatinib Mesylate ; pharmacology ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; metabolism ; physiopathology ; Phenanthrenes ; pharmacology