Animals ; Cholesterol ; blood ; Hyperlipidemias ; blood ; drug therapy ; Leptin ; pharmacology ; therapeutic use ; Male ; Mice ; Mice, Inbred Strains

Objective To study topiramate′s neuroprotection on primary cultured hippocampal neurons which were injuried by glutamate and its mechanism.Methods The primary cultured hippocampal neurons were made as the research object,and excitotoxicity model was exected with glutamate.Hippocampal neuron survival was assessed by MTT method and hippocampal neuron mitochondrial membrance potential(MMP) was evaluated by fluorescence microscope and flow cytometry.Results Hippocampal neuron survival of normal control was(98.4?0.8)%,and the survival of glutamate model group was(59.6?3.2)%,at the same time,two topiramate′s groups′ cell survivals was(74.1?0.5)% and(79.2?3.4)%,and topiramate with two levels all could obviously increase hippocampal neuron survival((P

This study was intended to enhance the resistance of cultured endothelial cells (EC) to fluid shear stress and clarify the possible mechanism.A modified parallel plate flow apparatus was used to compare the strength between the grafts and the endothelial cells under shear stress condition and static condition. The dynamic change of cytoskeletal actin filaments and the effects of different adhesive proteins coated on the strength of EC adhesion to the glass were studied. The results showed that the number of cells retention of the shear stress-conditioned group was significantly larger than that of the static group. Precoated fibronectin and laminin significantly promoted the adherence of the EC cultured in a steady environment but seemed to have no effect on the EC cultured under flow condition. The results suggest that the vascular endothelial cell cytoskeleton, stress fiber and the shape of EC reorganize in response to long term fluid-imposed shear stress, and the endothelial cells become tightly adherent to the grafts.

A series of 4-(2-acetoxybenzoylamino) butyrate derivatives were designed and synthesized. All of the novel 12 compounds (7a-7k) were synthesized from gamma-aminobutyric acid (1) as starting material, and their structures were confirmed with IR, 1H NMR, EI-MS and elemental analysis. Preliminary pharmacological test in vitro showed that most of these title compounds possessed antiepileptic activity. Compounds 7i-7k displayed strong antiepileptic activity and are worth for further development. Compounds 4, 7d-7h showed moderate antiepileptic activity. The structure-activity relationship of 4-(2-acetoxybenzoylamino) butyrate derivatives is also discussed preliminarily.
4-Aminopyridine ; Animals ; Anticonvulsants ; chemical synthesis ; chemistry ; therapeutic use ; Butyrates ; chemical synthesis ; chemistry ; therapeutic use ; Drug Design ; Epilepsy ; chemically induced ; drug therapy ; Female ; Lethal Dose 50 ; Male ; Mice ; Molecular Structure ; Random Allocation ; Structure-Activity Relationship ; gamma-Aminobutyric Acid ; chemistry

Carnosic acid (CA) is the main phenolic diterpenoid active ingredient in plants such as rosemary and sage, and has antiviral, antioxidant, anti-inflammatory effects and so on, however, its antiviral activity against influenza virus infections was not reported. In this study, antiviral activities against influenza A virus infections of three main bioactive ingredients from rosemary, including rosmarinic acid, CA and ursolic acid, were evaluated using virus titer titration assay, and CA showed remarkable inhibition on influenza H5N1 replication in A549 cells. The antiviral activity of CA was further confirmed and its mechanism of action was investigated using the indirect immunofluorescence assay (IFA), Western blot and real-time fluorescence quantification polymerase chain reaction (qRT-PCR). The results showed that the 50% effective concentration (EC₅₀) of CA against influenza H5N1 in A549 cells and MDCK cells were 4.30 and 3.64 μmol·L^-1, respectively. Meanwhile, CA also showed inhibition on influenza virus 2009panH1N1 (EC₅₀: 10.1 μmol·L^-1) and H3N2 (EC₅₀: 12.8 μmol·L^-1) replications in A549 cells. Mechanistic studies showed that antiviral activity of CA is related to its induction of heme oxygenase-1 (HO-1) in A549 cells and suppression on production of reactive oxygen in H5N1-infected cells.

OBJECTIVETo evaluate the effects of taurine in diet on the expression of inducible nitric oxide synthase (iNOS) in rat lung induced by silica.

METHODSWistar rats were established by direct tracheal instillation of silica into rat lungs exposed surgically, and the animals of taurine-treated group were silica-instilled with a diet containing taurine. The taurine concentration of serum was analyzed by means of HPLC. The expression of iNOS protein in paraffin-embedded lung sections with Streptavidin/peroxidase (SP) immunohistochemistry on tissue microarray was measured by Image-Pro Plus.

RESULTSThe concentration of taurine in serum of taurine-treated group was significantly higher than those in saline-treated and silica-treated groups (P < 0.05). The activities of total NOS and iNOS in BALF supernatant and iNOS positive area percentage of rat lung in silica-treated group were at the peak on 14th day, which were 1.84 U/ml, 1.12 U/ml and 5.42% more respectively than those in saline-treated group (P < 0.05). There were no significant differences between taurine-treated group and silica-treated group in total NOS and iNOS activities of BALF supernatant, and iNOS positive area of the lung (P > 0.05).

CONCLUSIONTreatment with taurine hardly influences on the increase in expression of nitric oxide synthase in rat lung induced by silica dust.

Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Female ; Lung ; drug effects ; enzymology ; Male ; Nitric Oxide Synthase Type II ; biosynthesis ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Taurine ; blood ; pharmacology

OBJECTIVETo investigate the effect of leptin on collagen systhesis in wounded rats.

METHODSThirty male Wistar rats, weight (180 +/- 20)g, were randomly divided into three groups (n = 10) by weight: normal depilation group, wound control group and leptin treatment group and ten rats were included in each group. A full-thickness defect measuring 2 x 2.5 cm was made in the back of rats in wound control group and leptin treatment group. Each wound in rats of leptin treatment group was applied topically with 0.1 ml leptin solution (2.0 microg leptin), daily for 7 days and that of wound control group with equivalent saline solution. All rats were killed and then granulation tissues samples and skin were collected to examine the synthesis of collagen.

RESULTSHydroxyproline content in granulation tissues of in leptin treatment group (33.92 +/- 3.09) mg/g were significantly increased than those in control group (29.55 +/- 3.59 mg/g, P < 0.05). The mRNA expressions of collagen I and III were significantly enhanced in leptin treatment group (0.96 +/- 0.09, 0.09 +/- 0.06) than those in control group (0.80 +/- 0.03, 0.08 +/- 0.03). The levels of type I and III collagen were significantly increased in leptin treatment group than those in control group.

CONCLUSIONLeptin applied topically can accelerate wound healing through enhancing gene expression of type I and III collagen and synthesis of collagen in wound tissue.

Administration, Cutaneous ; Animals ; Collagen Type I ; genetics ; metabolism ; Collagen Type III ; genetics ; metabolism ; Leptin ; administration & dosage ; therapeutic use ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Wound Healing ; drug effects ; Wounds and Injuries ; drug therapy

OBJECTIVETo evaluate the effects of taurine in diet on the expression of type I and III collagen and collagen ratio at different time points in rats lung by image process technology.

METHODSWistar rats were randomly divided into three groups: the saline instilled with a control diet (the saline treated group); silica instilled with a control diet (the silica treated group); and silica instilled with a diet containing 2.5% taurine (the taurine treated group). Animal models were established by the direct tracheal instillation of silica into rat lungs exposed surgically. The taurine concentration of serum was analyzed by means of HPLC. Paraffin embedded lung sections were stained with Sirius red. Polarization microscopy and Image Pro Plus Version 4.5 for windows were used for detecting type I and III collagen.

RESULTSThe concentration of taurine in serum of the taurine treated group was significantly elevated compared to the saline treated and silica treated group (P < 0.05 or P < 0.01). Sirius red polarization microscopy showed that type I and III collagen positive area percentage were elevated in the silica treated rats compared with the saline treated group. On the 7th, 14th, 21st, 28th day after silica instillation type I collagen positive area percentage was increased by 3.84, 3.77, 3.73, 9.83 respectively (P < 0.01), and type III collagen positive area percentage were elevated by a little in the silica treated rats compared with saline treated group. The taurine treatment significantly decreased elevation of silica type I collagen positive area percentage of lung by 2.39, 1.62, 7.13 at the 7th, 21st, 28th day respectively (P < 0.05 or P < 0.01), and type III collagen positive area percentage of lung by 2.62 at the 28th day (P < 0.05) compared with the silica treated group. The ratio of type I to III collagen was increased from the 7th day to 28th day after silica instillation, and reached 1.87 at the 28th day with the maximal ratio in the silica-treated group.

CONCLUSIONTreatment with taurine can effectively attenuate type I and III collagen expression in the rat lung induced by silica particles at different time points in our study.

Animals ; Collagen Type I ; biosynthesis ; Collagen Type III ; biosynthesis ; Female ; Lung ; drug effects ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Taurine ; pharmacology

Autophagy, an evolutionarily conserved process by which components of the cell are degraded in lysosomes, may facilitate survival of cancer cells under stress conditions. 8-Azaguanine (8-AG), an inhibitor of purine nucleotide biosynthesis, shows antineoplastic activity in multiple tumor cells. However, chemoresistance has restricted its development as an anticancer agent, and the mechanism of 8-AG resistance is not fully understood. We report here that 8-AG induces a protective autophagy to eliminate its cytotoxicity, and inhibition of autophagy increases cellular sensitivity of cancer cells to 8-AG treatment. Using HepG2 or SMMC-7721 hepatic cancer cell lines, we found that 8-AG inhibited cell viability and induced intrinsic apoptosis, accompanied by the up-regulation of the pro-apoptotic protein BimS, one of Bim (also known as BCL-2-like protein 11, BCL2L11) isoforms. Furthermore, 8-AG treatment enhanced the autophagy flux by promoting the dephosphorylation and activation of Unc-51-like autophagy activating kinase 1 (ULK1) via Akt/mTORC1 (mammalian target of rapamycin complex 1) signaling inhibition. Depletion of autophagy-related gene 7 (ATG7) markedly enhanced the level of BimS, and promoted cell death in response to 8-AG. 8-AG in combination with autophagy inhibitor chloroquine (CQ) or bafilomycin A1 (Baf A1) promoted the 8-AG-induced apoptosis in hepatic cancer cells. Altogether, these findings suggest that autophagy promotes chemoresistance of cancer cells for 8-AG, and blocking autophagy increases cellular sensitivity of cancer cells to 8-AG treatment.

OBJECTIVE: To determine the protective effects and mechanism of ulinastatin on the lung injury during cardiopulmonary bypass (CPB). METHODS: Thirty patients with rheumatic heart disease (RHD) were divided into 2 groups randomly. The ulinastatin group (Group U, n = 15) received 1 x 10(4)U/kg ulinastatin intravenously before the CPB and the same amount of ulinastatin was added into the primary solution. The control group (Group C,n = 15) received normal saline instead of ulinastatin. A brochioalveolar lavage was performed at 2 h after the cardiopulmonary bypass. Polymorphonuclear neutrophil elastase, tumor necrosis factor-alpha and MDA contents in the brochioalveolar lavage fluids were measured, and the lung oxygenate index was measured preoperatively and at 1 and 4 h after CPB termination. RESULTS: Polymorphonuclear neutrophil elastase, tumor necrosis factor-alpha and MDA contents of Group U in the brochioalveolar lavage fulids were significantly lower than those of Group C (P < 0.05), and the lung oxygenate index of Group U at 1 and 4 h after CPB termination was also significantly lower than that of Group C. A significant increase of lung oxygenate index occurred in both groups at 1 and 4 h after CPB when compared with the same group at the baseline before CPB (P < 0.05). CONCLUSION Ulinastatin has the protective effects on the lung injury during CPB by decreasing polymorphonuclear neutrophil elastase, alleviating lung inflammatory reaction and reducing oxygen free radicals.
Adolescent ; Adult ; Aged ; Bronchoalveolar Lavage Fluid ; Cardiopulmonary Bypass ; Female ; Glycoproteins ; therapeutic use ; Humans ; Leukocyte Elastase ; metabolism ; Male ; Middle Aged ; Protective Agents ; therapeutic use ; Respiratory Distress Syndrome, Adult ; prevention & control ; Rheumatic Heart Disease ; surgery ; Trypsin Inhibitors ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism