Acupuncture Therapy ; Adult ; Combined Modality Therapy ; Female ; Humans ; Male ; Musculoskeletal Manipulations ; Osteitis ; pathology ; therapy ; Sacroiliac Joint ; pathology ; Sclerosis ; therapy ; Young Adult

Objective:To investigate the mechanism and effects of autophagy on cisplatin(DDP)-induced apoptosis in human gas-tric cancer cell line SGC7901. Methods:Cell proliferation was determined by an MTT assay after the SGC7901 cells were treated with DDP and/or chloroquine. Cell apoptosis was determined by flow cytometry. Autophagy and related protein expressions were detected by Western blot. Autophagy was quantitatively analyzed by fluorescence microscopy after monodansylcadaverine staining was per-formed. Results:The cells were treated with 5 mg/L of DDP for 24 h, the rate of cell apoptosis was (21.07 ± 2.12)%. Autophagy, char-acterized by an increase in the number of autophagic vesicles and LC3-II protein level, was observed in DDP-treated cells. After autoph-agy was inhibited by chloroquine, the rate of cell apoptosis was increased to (30.16 ± 3.54)%. In addition, caspase-3 and P53 protein levels were increased, but Bcl-2 protein was decreased. Conclusion:Autophagy protected human gastric cancer cell line SGC7901 from DDP-induced apoptosis. In addition, the inhibition of autophagy could promote apoptosis. The combined therapy of DDP and chlo-roquine may be a promising therapeutic strategy for gastric cancer.

Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemical synthesis ; chemistry ; pharmacology ; Camptothecin ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; DNA Damage ; Humans ; Topoisomerase I Inhibitors ; Topotecan ; chemical synthesis ; chemistry ; pharmacology ; Tumor Cells, Cultured ; drug effects

Objective To discuss the effect of Dickkopf-1 (DKK-1) on Wnt singal pathway during the differentiation of osteoblast in vitro.Methods The osteoblasts were obtained from the new rats and cultured in vitro.The 3 passages were divided into control group and DKK-1 group.The cells were cultured in DKK-1 and normal saline for morphogical detection,ALP activity detection and osteoblasts stained at 1 st,6th,12th,21st day.The Wnt was detected by RT-PCR.Results After cultured by the DKK-1 in vitro,the ALP and mineralization of osterblasts staining were prlonged with culture time.Compared with control group,the expression of Wnt was significantly reduced at the 21st day after induction (t =0.278,P ＜ 0.05).Conclusion DKK-1 can regulate the expression of Wnt during osteoblast differentiation,suggests that Wnt may be involved in osteoblast differentiation and can affect bone remodeling process.

In recent years, the incidence and mortality rate of invasive fungal infection have increased dramatically, and it is of great significance to develop novel antifungal agents with new chemical structure and new mode of action. In this review, novel antifungal lead compounds reported from 2007 to 2009 are reviewed. Moreover, their chemical structures, antifungal activities and structure-activity relationships have been summarized, which can provide useful information for future study of antifungal agents.
Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Fungi ; drug effects ; Heterocyclic Compounds ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Lipopeptides ; chemistry ; pharmacology ; therapeutic use ; Molecular Structure ; Mycoses ; drug therapy ; Nitriles ; chemistry ; pharmacology ; therapeutic use ; Plant Extracts ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Pyridines ; chemistry ; pharmacology ; therapeutic use ; Quinazolines ; chemistry ; pharmacology ; therapeutic use ; Quinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Thiazoles ; chemistry ; pharmacology ; therapeutic use ; Triazoles ; chemistry ; pharmacology ; therapeutic use

Acyltransferases ; antagonists & inhibitors ; chemistry ; Animals ; Antifungal Agents ; chemical synthesis ; pharmacology ; Benzofurans ; chemical synthesis ; pharmacology ; Benzothiazoles ; chemical synthesis ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; pharmacology ; Fungi ; drug effects ; enzymology ; Imidazoles ; chemical synthesis ; pharmacology ; Molecular Structure

In recent years, the incidence of infections caused by invasive fungal pathogens has increased dramatically. However, most antifungal agents used in clinic have many drawbacks and cannot meet the demand of the clinical use. Therefore, for the development of new generation of antifungal agents, it is of great significance to find antifungal lead compounds with novel chemical scaffolds and new mode of action. Novel antifungal lead compounds reported in recent years are reviewed. Their chemical structures, antifungal activity and structure-activity relationship are discussed in detail, and current problems and trends in future research are also emphasized.
4-Butyrolactone ; analogs & derivatives ; chemistry ; pharmacology ; Animals ; Antifungal Agents ; chemistry ; pharmacology ; Berberine ; analogs & derivatives ; chemistry ; pharmacology ; Cholestanols ; chemistry ; pharmacology ; Cycloleucine ; analogs & derivatives ; chemistry ; pharmacology ; Fungi ; drug effects ; Heterocyclic Compounds ; chemistry ; pharmacology ; Humans ; Lactones ; chemistry ; pharmacology ; Molecular Structure ; Naphthoquinones ; chemistry ; pharmacology ; Pyridines ; chemistry ; pharmacology ; Structure-Activity Relationship

To clarify the important functional residues in the active site of N-myristoyltransferase (NMT), a novel antifungal drug target, and to guide the design of specific inhibitors, multiple sequence alignments were performed on the NMT family and thus evolutionary trace was constructed. The important functional residues in myristoyl CoA binding site, catalytic center and inhibitor binding site of NMT family were identified by ET analysis. The trace residues were mapped onto the active site of CaNMT. Trpl26, Asn175 and Thr211 are highly conserved trace residues and do not interact with current NMT inhibitors, which are potential novel drug binding sites for the novel inhibitor design. Pro338, Leu350, Ile352 and Ala353 are class-specific trace residues, which are important for the optimization of current NMT inhibitors. The trace residues identified by ET analysis are of great importance to study the structure-function relationship and also to guide the design of specific inhibitors.
Acyl Coenzyme A ; metabolism ; Acyltransferases ; chemistry ; genetics ; metabolism ; Amino Acid Sequence ; Animals ; Binding Sites ; Conserved Sequence ; Enzyme Inhibitors ; chemistry ; pharmacology ; Evolution, Molecular ; Humans ; Imidazoles ; chemistry ; pharmacology ; Models, Molecular ; Molecular Sequence Data ; Oligopeptides ; chemistry ; pharmacology ; Phylogeny ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid

OBJECTIVETo investigate the systemic changes of iron metabolism following manganese exposure.

METHODSNinety-seven welders and 91 workers with no history of exposure to manganese were recruited from the same factory in Beijing serving as the exposure group and the control group respectively. The welding rods used were type J422. The concentration of the manganese in the air of the work place was determined respectively with the national standard method. The serum iron and manganese, ferritin, transferrin and transferrin receptors were measured with the graphite furnace atomic absorption spectrophotometry and ELISA in both groups.

RESULTSThe permissible concentration-STEL of ambient Mn in welders' breathing zone ranged from 0.53 mg/m(3) to 2.19 mg/m(3), while the permissible concentration-TWA of ambient Mn was between 0.29 mg/m(3) and 0.92 mg/m(3) in the breathing zone of the workplace. Serum Mn and Fe concentrations in welders were about 1.40 times (P < 0.0l) and 1.2 times (P < 0.01), respectively, higher than those of control subjects. At the same time, the transferrin concentrations in serum were significantly higher (about 1.2 times, P < 0.05) in welders than in controls. In contrast, transferrin receptors were significantly lower (about 1.2 times) in exposed subjects than controls (P = 0.001). There was no difference in serum ferritin between the two groups (P = 0.112). Although there was no significant trend, the serum ferritin level was increased by 18% in comparison with that of the control. The abnormal percentage of serum Fe and Serum Mn in welders were 55.67% and 67.01% respectively, higher than those of control subjects. In addition, the correlations between all indicators and the duration of employment were not observed.

CONCLUSIONThe long term exposure to the manganese can induce the disorder of the iron metabolism, which is found in the expression of increase of the serum iron and transferrin as well as the decrease of transferrin receptors.

Female ; Ferritins ; blood ; Humans ; Iron ; metabolism ; Iron Metabolism Disorders ; chemically induced ; Male ; Manganese ; adverse effects ; Occupational Exposure ; adverse effects ; Receptors, Transferrin ; blood ; Transferrin ; analysis ; Welding

AIMTo study the effect of experimental left varicocele (ELV) on epididymal structure and function in adolescent Sprague-Dawley rats.

METHODSELV was induced by partial ligation of the left renal vein. Sham-operated animals served as the controls. Four and 8 weeks after the operation, the histological, ultrastructural and biochemical (alpha-glucosidase activity and carnitine content) changes in different segments of the epididymis were observed.

RESULTSIn the treated animals, there were degeneration of the epididymal epithelium and edema of the interstitial tissue; numerous shedding cells, residual bodies, deformed sperm and macrophages appeared in the epididymal lumen. Morphometric measurement indicated a significant reduction in the epididymal tubular diameter (P<0.05) and a significant increase in the epididymal interstitial area (P<0.05) compared with the controls. Ultrastructural study showed sparse microvilli of the columnar epithelium, increased and enlarged lysosomes in the principal cells with defected organelles and the presence of large cytoplasmic vacuoles. The protein and carnitine contents and the alpha-glucosidase activity in the caput, corpus and cauda epididymis of the ELV rats were lower than those of the controls (P<0.05).

CONCLUSIONThere were structural and functional changes in the epididymis of adolescent ELV rats, which may contribute to the infertility caused by varicocele.

Animals ; Carnitine ; metabolism ; Epididymis ; enzymology ; pathology ; physiopathology ; ultrastructure ; Male ; Microscopy, Electron ; Rats ; Rats, Sprague-Dawley ; Varicocele ; enzymology ; pathology ; physiopathology ; alpha-Glucosidases ; metabolism