Sphingolipids, especially ceramide and S1P, are structural components of biological membranes and bioactive molecules which participate in diverse cellular activities such as cell division, differentiation, gene expression and apoptosis. Emerging evidence demonstrates the role of sphingolipids in hepatocellular death, which contributes to the progression of several liver diseases including ischaemia-reperfusion liver injury, steatohepatitis or hepatocarcinogenesis. Furthermore, some data indicate that the accumulation of some sphingolipids contributes to the hepatic dysfunctions. Hence, understanding of sphingolipid may open up a novel therapeutic avenue to liver diseases. This review focuses on the progress in the sphingolipid metabolic pathway with a focus on hepatic diseases and drugs targeting the sphingolipid pathway.
Apoptosis ; Ceramides ; metabolism ; Fatty Liver ; metabolism ; physiopathology ; Humans ; Liver Diseases ; metabolism ; physiopathology ; Lysophospholipids ; metabolism ; Reperfusion Injury ; metabolism ; physiopathology ; Sphingolipids ; metabolism ; Sphingosine ; analogs & derivatives ; metabolism

Specific primers 1CaA/1CaB for full cry1C gene in Bacillus thuringiensis subsp.colmeri strain 15A3 were designed. The 4.0kb PCR product included the whole ORF and regulation region of cry1C gene. This PCR product was linked with shuttle vector pHT315 by two cloning steps. The recombined plasmid pHT-1C was electroporated into Bacillus cereus 9509, a kind of bacteria that beneficial to crops. The transformant could produce bipyramidal-shaped parasporal inclusions. The 60kD protein band was detected by SDS-PAGE. The bioassay result showed that the cry1C gene transformant of Bc 9509 had insecticidal activity to Spodoptera exigua.

The high-copy-number plasmid pcDNA3.1+ is unstable within S almonella typhimurium. A novel plasmid pmcDNA3.1+ was constructed by removin g the promoter sequence of ampicillin resistance gene (bla gene) in plasmid pcDNA3.1+. In contrast to pcDNA3.1+, pmcDNA3.1+ was stable within Salmonel la typhimurium SL7207 in LB medium with or without ampicillin. Further experi ments showed the ?-lactamase activity of Salmonella typhimurium SL7207(pmc DNA3.1+) was apparently lowered than that of Salmonella typhimurium SL7207( pcDNA3.1+) and the high ampicillin concentration was maintained longer in LB me dium culturing Salmonella typhimurium SL7207(pmcDNA3.1+). When mice were a dministered with Salmonella typhimurium SL7207(pmcDNA3.1+) intraperitoneall y, more than 95% of Salmonella cells separated from the spleen still harbore d the plasmid pmcDNA3.1+ 7 days later; but 99% of Salmonella cells lost the plasmid pcDNA3.1+ at day 3 in mice innoculated with Salmonella typhimurium SL7207(pcDNA3.1+). By lowering the expression of bla gene, the rapid deco mposition of ampicillin in LB medium was avoided and the metabolic pressure was relieved for the host cells. This method offers a solution for the problem of t he instability of high-copy-number plasmid within Salmonella typhimurium.

The dense extracellular matrix (ECM) of the tumor severely limits the deep penetration of nanomedicine and weakens its anti-tumor effect. Based on this, the yeast vesicle biomimetic nanomedicine with active deep penetration ability of tumor tissue was designed and developed for enhanced tumor therapy. Results of characterization showed that the yeast cell vesicles (YCV) displayed a spherical morphology with diameter of around 100 nm and was well dispersed. Then the chemotherapeutic drug doxorubicin (DOX) was selected as a model drug, and DOX was loaded into YCV to obtain YCV/DOX through electrostatic interaction, the encapsulation efficiencies of DOX were calculated as 82.5%. The drug release profile of YCV/DOX implied that DOX release showed a manner of pH-dependent, it may be that pH has affected the electrostatic effect of YCV and DOX. Compared with liposomes (Lipo), in vitro cell experiments showed that YCV from natural sources had stronger permeability in three-dimensional multicellular spheres. It is speculated that the mechanism may be good deformation capacity of YCV. A 4T1 xenograft tumor model was established to evaluate the therapeutic efficacy of YCV/DOX. The results suggested that YCV/DOX has stronger tumor tissue penetration ability and could effectively inhibit the tumor growth. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Zhengzhou University. This study brings new ideas for the development of biomimetic nanomedicine to overcome the ECM of solid tumors.

To provide a scientific basis for the selection of the appropriate drying method for Mentha Haplocalyx Herba (MHH), determine 2 monoterpenes, 4 phenolic acids and 5 flavonoids in MHH by GC-MS and UPLC-TQ-MS methods, and investigate the effects of the drying methods on the changes in contents of these analytes. The qualities of products obtained with different drying methods were evaluated by the multivariate statistical method of Technique for Order Preference by Similarity to Ideal Solution (TOPSIS). Results showed that the drying methods had the greatest impact on menthol, caffeic acid, and rosemary acid, which were followed by chlorogenic acid and diosmetin-7-O-glucoside. The contents in these analytes processed with hot-air-drying method were higher than those with microwave-drying and infrared-drying methods at the same temperatures. The contents in these analytes processed under low temperature (40-45 °C) were higher than those under higher temperature (60-70 °C). Above all, the contents in phenolic acids processed with microwave fixation (exposed under microwave at 100 °C for several minutes) were obviously higher than those of not being processed, showing an inhibition of some enzymes in samples after fixation. The TOPSIS evaluation showed that the variable temperature drying method of 'Hot-Air 45-60 °C' was the most suitable approach for the primary drying processing of MHH. The results could provide the scientific basis for the selection of appropriate drying method for MHH, and helpful reference for the primary drying proces of herbs containing volatile chemical components.
Desiccation ; methods ; Flavonoids ; analysis ; Hydroxybenzoates ; analysis ; Mentha ; chemistry ; Monoterpenes ; analysis

Objective To explore the effects of stimulating vagus nerve with pulse current on peripheral blood CD4+T lymphocyte of rats with collagen induced arthritis and its mechanism.Methods To duplicate model rats of experimental arthritis(EA)by intradermal injection of Ⅱtype collagen,divide the rats into 2 groups:vagus nerve stimulation(VNS)group and sham operated group.Rats in VNS group were stimulated at the left cervical vagus nerves for 30 minutes a day with constant square wave,pulse current with intra train of 16 Hz,pulse duration of 1.0 ms,train duration of 10 s,interstimulus interval of 1.5 min and intensities of 3.0 mA.Then flow cytometry and immunofluorescence methods were used to detect the activation of CD4+T lymphocytes(expressing CD71)and the expression of nicotinic acetylcholine receptors alpha 7(nAChR?7)and choline acetyltransferase(ChAT)in peripheral blood CD4+T lymphocytes.Results In VNS group,the expression of nAChR?7 and ChAT were significantly raised in CD4+ T cells at 1st weekend(Pa

ObjectiveTo investigate the iodine nutritional status of pregnant women,newborn heel blood thyroid stimulating hormone(TSH) level and their relationship with urinary iodine(UI) level during pregnancy in Zhoupu and Kangqiao districts of Pudong New Area of Shanghai.Methods A total of 993 urinary samples(the first,second and third trimesters of pregnancy were 200 people,respectively),breast feeding(193 people) and non-pregnant women (200 people) in Zhoupu and Kangqiao districts of Pudong New area were collected from Apr 2009 to Dec 2010.Two hundred copies of neonatal heel blood samples were collected.Median of UI was measured by arsenic-cerium catalysis.TSH in neonatal heel blood was analyzed 72 h after birth by time resolved fluoroisnmunoassay(TRFIA).ResultsMedian UI of all pregnant women was 161.35 μg/L,and that in third trimesters of pregnancy( 126.35 μg/L) was lower than that of the first,the second,the breast feeding and non-pregnant women (178.80,180.50,167.90,163.40 μg/L,all P＜ 0.05).The percentage of UI level less than 150 μg/L in the third trimester[57.5％(115/200) ] was higher than that of the first[39.0％(78/200) ],the second[39.5％(79/200) ],the breast feeding [ 16.6％ (32/193) ] and non-pregnant women [ 23.0％ (46/200) ],respectively (all P ＜ 0.05).The percentage of UI level higher than 300 μg/L in the first [9.0％(18/200)],the second[8.0％(16/200) ] and the third trimester [ 5.0％ ( 10/200 ) ] of pregnancy was lower than that of the breast feeding [ 20.2％ (39/193) ] and nonpregnant [20.5％(41/200) ] women,respectively(all P ＜ 0.05).The level of neonatal heel blood TSH was(2.92 ± 1.83)mU/L,the range was 0.01 - 9.76 mU/L,11.0％(22/200) of the neonates heel blood TSH level(5 mU/L)exceeded the ratio of World Health Organization (WHO) standard ( ＜ 3％ ) suitable for iodine nutrition.Conclusions The overall level of iodine nutrition among pregnant women in Zhoupu and Kangqiao districts of Pudong New Area of Shanghai is in the appropriate range,but the pregnant women in the third trimester is in mild iodine deficiencies,and the neonates in these districts may be prone to iodine deficiency.Monitoring of iodine nutrition of pregnant women should be strengthened and iodine supplementation should be done scientifically.

OBJECTIVETo investigate the inhibition effect of curcumin on the proliferation of the human esophageal carcinoma cell line Ec109 and its impact on PEN/PI3K/Akt signaling pathway.

METHODSEsophageal carcinoma Ec109 cells were cultured in vitro conventionally and were treated with curcumin at different concentrations. The cell proliferation level was examined by MIT colorimetry, the ultrastructure of curcumin-treated Ec109 cells were detected with transmission electron microscope (TEM) and cell apoptosis was observed by FCM with AnnexinV-FITC/PI double staining. The protein levels of PTEN, Akt, GSK3P and Caspase 3 of curcumin-treated Ec109 cells were detected by Western blot.

RESULTSMTT test showed that curcumin could inhibit the proliferation of Ec109 cells in a time and concentration-dependent manner. TEM examination indicated that curcumin could induce Ec109 cell apoptosis. FCM detection showed that Ec109 cell apoptotic rate increased significantly with the increase of drug concentration. On the other hand, curcumin could promote the expression of PTEN, GSK3beta and Caspase 3 yet reduce the expression of Akt.

CONCLUSIONCurcumin could obviously up-regulate the expression of PTEN, GSK3beta and Caspase 3, surpress PI3K/Akt signaling pathway and hence inhibit the proliferation of Ec109 cells.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Oncogene Protein v-akt ; metabolism ; PTEN Phosphohydrolase ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Signal Transduction ; drug effects

To construct the Bac-to-Bac expression system of Bombyx mori nucleopolyhedrovirus (BmNPV), a transfer vector was constructed which contained an Escherichia coli (E. coli) mini-F replicon and a lacZ: attTN7: lacZ cassette within the upstream and downstream regions of the BmNPV polyhedrin gene. B. mori larvae were cotransfected with wild-type BmNPV genomic DNA and the transfer vector through subcutaneous injection to generate recombinant viruses by homologous recombination in vivo. The genomic DNA of budded viruses extracted from the hemolymph of the transfected larvae was used to transform E. coli DH10B. Recombinant bacmids were screened by kanamycin resistance, PCR and restriction enzyme (REN) digestion. One of the bacmid colonies, BmBacJS13, which had similar REN profiles to that of wild-type BmNPV, was selected for further research. To investigate the infectivity of BmBacJS13, the polyhedrin gene was introduced into the bacmid and the resultant recombinant (BmBacJS13-ph) was transfected to BmN cells. The budded viruses were collected from the supernatant of the transfected cells and used for infecting BmN cells. Growth curve analysis indicated that BmBacJS13-ph had a similar growth curve to that of wild-type BmNPV. Bio-assays indicated that BmBacJS13-ph was also infectious to B. mori larvae.

Forty batches of Lonicerae Japonica Fse i collected extensively and prepared as the test solution. Their chromatographic fingerprints and anti-influenza virus IC50 value (half maximal inhibitory concentration) were determined respectively. Then Unscrambler software was used, and spectrum-efficient correlation analysis was done for chromatographic fingerprints data and IC50 data by partial least squares regression method, to establish spectrum-efficient correlation model for anti-influenza virus of Lonicerae Japonicae Flos. Then the other 10 batches of Lonicerae Japonicae Flos were used to verify the model and explore the adaptability of this spectrum-efficient correlation model based on partial least squares regression method. The mathematical model obtained R2 of 0.969489 and RM-SEC of 0.070691 for calibration set; R2 of 0.959042 and RMSECV of 0.084005 for cross validation set. The verification experiment results showed that the relative error between the predicted values and measured values was within 10% in all 10 hatches, and within 5% in 80% of them. The results showed that the established spectrum-efficient correlation model could be used to evaluate the biological activity of anti-influenza virus of Lonicerae Japonicae Flos by determining its HPLC fingerprints.
Antiviral Agents ; analysis ; pharmacology ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Flowers ; chemistry ; Least-Squares Analysis ; Lonicera ; chemistry ; Molecular Structure ; Orthomyxoviridae ; drug effects