Genetic Variation ; Humans ; Ticlopidine ; analogs & derivatives ; pharmacokinetics ; pharmacology

The changes in intracellular Ca and metabolism of lipid in human monocyte-macrophages as interacted with glycosylated LDL (glc-LDL) were studied and compared with normal LDL group. The intracellular Ca in glc-LDL group was higher than in normal LDL group (P

The study reports the detection of neuroprotective effect of 10 kinds of coumarin derivatives and explores their possible mechanism. MTT method was used to screen the neuroprotective effect of 10 coumarin derivatives on neurotoxic agents (Aβ25-35 and rotenone) or OGD (oxygen-glucose deprivation). A compound with better protective effect was obtained. Then the effect of this compound on neurotoxic agents on PC12 was detected by the morphological observation. Furthermore, the effect of compound 3 on microglia with lipopolysaccharide (LPS) induced inflammation was detected. And the inflammatory factor was tested. Finally, direct free radical scavenging ability was detected. Compound 3 was found to be the best compound through three neurons toxic models. Not only compound 3 ameliorated cell viability reduced by three neurons toxic models, but also significantly inhibited the production of inflammatory factor (TNF-α and IL-1β). And its free radical scavenging ability is very good, especially the effect on superoxide anion, which is comparable with vitamin C. The significant scavenging effect of compound 3 on superoxide anion might be the mechanism of the neuroprotection. Compound 3 as a potential neural cell protective agent merits further investigation.
Animals ; Coumarins ; chemistry ; Free Radical Scavengers ; chemistry ; Inflammation ; Microglia ; drug effects ; Neurons ; drug effects ; Neuroprotective Agents ; chemistry ; PC12 Cells ; Rats

BACKGROUNDDiabetic myocardiopathy is characterized by myocardial interstitial fibrosis and cardiac dysfunction. Statins were found to exert protective effects on cardiovascular disease by suppressing activation of small G proteins, independently of their lipid-lowering effect. The study investigated the effect of fluvastatin on myocardial interstitial fibrosis, cardiac function and mechanism of its action in diabetic rats.

METHODSTwenty-four male SD rats were randomly assigned to 3 groups: control rats (n = 8), streptozotocin (STZ)-induced diabetic rats (n = 8), and diabetic rats treated with fluvastatin (administered fluvastatin orally, 10 mg/kg body weight per day, n = 8). Twelve weeks later, miniature cardiac catheter was inserted into the left ventricle to conduct hemodynamic examination. Then myocardium tissues were collected, collagen content was detected by picro-sirius red staining, real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of connective tissue growth factor (CTGF), and Western blotting was used to detect the protein expression of CTGF. Rho activity was determined by pull-down assay.

RESULTSAfter 12 weeks, the left ventricular systolic pressure (LVSP) and maximum rate of left ventricular (LV) pressure rise and fall (+dP/dt max and -dP/dt max) were significantly lower and left ventricular end diastolic pressure (LVEDP) was higher in the diabetic rats than those in the control rats (P < 0.01). Moreover, in LV myocardial tissue of diabetic rats the collagen content, fibronectin, mRNA and protein expression of CTGF and the activity of RhoA were all significantly increased compared with the control rats (P < 0.01). Administration of fluvastain obviously improved the cardiac function of diabetic rats, attenuated fibronectin expression, mRNA and protein expression of CTGF and the activity of RhoA in LV myocardium of diabetic rats.

CONCLUSIONSFluvastatin attenuates cardiac dysfunction and myocardial interstitial fibrosis of diabetic rat by inhibiting activity of RhoA to down-regulate the overexpression of CTGF, and Rho/Rho-kinase pathway may be an important target in the treatment of diabetic cardiomyopathy.

Animals ; Anticholesteremic Agents ; therapeutic use ; Blood Glucose ; metabolism ; Blotting, Western ; Cholesterol ; blood ; Connective Tissue Growth Factor ; metabolism ; Fatty Acids, Monounsaturated ; therapeutic use ; Fibrosis ; blood ; drug therapy ; metabolism ; Hemodynamics ; drug effects ; Immunohistochemistry ; Indoles ; therapeutic use ; Male ; Myocardium ; metabolism ; pathology ; Random Allocation ; Rats ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the life style, genetic and occupational risk factors of metabolic syndrome (MS) among policemen.

METHODS1:4 matched case-control study was used, based on physical examination data of Tianjin Policemen in 2010, 708 patients with MS were randomly selected as cases, which were matched with 2832 healthy controls on the basis of sex and age (+/- 1 year). An epidemiological investigations on the past exposure status of several possible risk factors was conducted, and the data were analyzed with conditional logistic regression.

RESULTSFifteen factors related to exposure were identified for MS through univariate conditional logistic regression analysis. Multivariate conditional logistic regression analysis suggested that, seven factors, such as family history of hypertension (OR = 2.406, 95% CI: 1.946-2.975), family history of diabetes (OR = 1.301, 95% CI: 1.043-1.623), smoking (OR = 1.357, 95%CI: 1.010-1.823), snoring (OR = 1.268, 95% CI: 1.043-1.543), work intensity (OR = 4.603, 95% CI: 3.767-5.623), occupational stressful events (OR = 1.524, 95% CI: 1.209-1.922), security policemen (OR = 1.453, 95% CI: 1.127-1.872) and criminal investigation policemen (OR = 2.792, 95% CI: 2.168-3.596), could significantly increase the risk of disease development, but dairy products (OR = 0.782, 95% CI: 0.619-0.989) was a protect factor for MS. The results from population attributable risk factors analysis showed that the control of smoking, snoring, work intensity, occupational stressful events can decreased the risk of MS to 16.26%, 11.71%, 56.87% and 8.97%, respectively.

CONCLUSIONMetabolic syndrome has became a significant public health problem among policemen, it's necessary to take measures on life style, occupational risk factors for reducing the incidence of MS, and improving the health level among policemen.

Adult ; Case-Control Studies ; Factor Analysis, Statistical ; Humans ; Logistic Models ; Male ; Metabolic Syndrome ; epidemiology ; genetics ; psychology ; Middle Aged ; Occupational Health ; Police ; Risk Factors ; Young Adult

AIMTo compare the effects of salvianolic acid B (Sal B) and Ginkgo biloba extract EGb 761 on beta-amyloid peptide (beta-AP) fibril formation and cytotoxicity to PC12 cells.

METHODSThe inhibitory effects of Sal B and EGb 761 on beta-AP1-40 fibril formation were determined by using fluorescence analysis with Thioflavin T (ThT) and electron microscopic image. beta-AP25-35 was aged by incubating at 37 degrees C for 7 d, then the protein was incubated with PC12 cells. The protective effects of Sal B and EGb 761 against cytotoxicity induced by aged beta-AP25-35 in PC12 cells were evaluated by MTT reduction assay and flow cytometric analysis. beta-AP25-35-induced accumulation of intracellular reactive oxygen species (ROS) was determined by fluorescence analysis.

RESULTSBoth Sal B and EGb 761 inhibited the formation of amyloid fibrils, protected PC12 cells from beta-AP25-35-induced cytotoxicity, and decreased ROS accumulation caused by beta-AP25-35. The effective doses of Sal B were far lower than those of EGb 761.

CONCLUSIONSal B was much more efficient than EGb 761 in inhibiting beta-AP aggregation and in protecting PC12 cells from beta-AP-induced cytotoxicity.

Amyloid beta-Peptides ; chemistry ; toxicity ; ultrastructure ; Animals ; Apoptosis ; drug effects ; Benzofurans ; isolation & purification ; pharmacology ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Flow Cytometry ; Ginkgo biloba ; chemistry ; Intracellular Fluid ; drug effects ; metabolism ; Microscopy, Electron ; Neuroprotective Agents ; isolation & purification ; pharmacology ; PC12 Cells ; Peptide Fragments ; chemistry ; toxicity ; ultrastructure ; Plant Extracts ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Rats ; Reactive Oxygen Species ; metabolism ; Salvia miltiorrhiza ; chemistry

OBJECTIVETo observe the effect of pioglitazone on advanced glycation end products (AGEs)-induced proliferation of vascular smooth muscle cells (VSMCs) and expression of peroxisome proliferators activated receptor gamma (PPARgamma). To investigate the possible role of PPARgamma in mediating AGEs induced proliferation of VSMCs.

METHODSPrimary cultures of smooth muscle cells from rat aorta were exposed to AGEs of different concentrations and different times prior to co-treatment with pioglitazone and AGEs. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay was adopted for the quantification of the cell proliferation ratio and PPARgamma expression was determined by RT-PCR and Western immunoblotting.

RESULTSAGEs increased the proliferation of VSMCs. AGEs treatment to VSMCs decreased mRNA and protein levels of PPARgamma in a time- and dose-related manner (P < 0.05). Pioglitazone inhibited the AGEs-induced proliferation of VSMCs in vitro.

CONCLUSIONSActivating PPARgamma in VSMCs, pioglitazone may play a role in anti atherosclerosis. The reduction in PPARgamma expression may be implicated in vascular smooth muscle cells proliferation and pathogenesis of atherosclerosis in patients with diabetes mellitus.

Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Glycation End Products, Advanced ; metabolism ; pharmacology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; PPAR gamma ; metabolism ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Thiazolidinediones ; pharmacology

BACKGROUNDGalectin-3 is the most recently identified advanced glycosylation end products (AGEs) binding protein. This study aimed to investigate the effects of AGEs and rosiglitazone on the expression and secretion of galectin-3 in cultured human renal mesangial cells (HRMCs).

METHODSHRMCs were incubated with different concentrations of AGE-bovine serum albumin (BSA) (0, 50, 100, 200, and 400 mg/L) for different time (0, 24, 36, 48, and 72 hours), and exposed to AGE-BSA in the presence of different concentrations of rosiglitazone (1, 10, and 100 micromol/L). The mRNA and protein expression of galectin-3 in HRMCs were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. The culture medium of HRMCs was collected and concentrated, and the content of galectin-3 in the medium was detected by Western blotting.

RESULTSBoth RT-PCR and Western blotting revealed that AGE-BSA up-regulated the expression of galectin-3 in HRMCs in a concentration- (P < 0.05) and time-dependent (P < 0.05) manner compared with the control. Compared with the control, AGE-BSA elevated the content of galectin-3 in the culture medium of HRMCs time- and concentration-dependently (P < 0.05, respectively). Both protein and mRNA expression of galectin-3, and its content in the medium of HRMCs exposed to different concentrations of rosiglitazone in the presence of AGE-BSA were increased compared with those of cells exposed to AGE-BSA alone (P < 0.05). Rosiglitazone increased the expression and secretion of galectin-3 in a dose-dependent manner (P < 0.05).

CONCLUSIONSAGEs up-regulates the expression and secretion of galectin-3 in HRMCs. Rosiglitazone further enhances the upregulation of galectin-3 in HRMCs induced by AGEs, which suggests that rosiglitazone may play a role of reno-protection via up-regulation of galectin-3.

Blotting, Western ; Cell Line ; Galectin 3 ; genetics ; secretion ; Glycation End Products, Advanced ; pharmacology ; Humans ; Hypoglycemic Agents ; pharmacology ; Mesangial Cells ; drug effects ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Serum Albumin, Bovine ; pharmacology ; Thiazolidinediones ; pharmacology

OBJECTIVE Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis. No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de-veloping new agents to treat GBM is important. This study aimed to evaluate the anti-tumor effect of evodiamine (Evo) on GBM cells, and to determine the underlying mechanisms involved. METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and 48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo-diamine(0-10 μmol·L-1)for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS)production was detected using dichlorofluorescein diacetate (DCFH-DA) staining. The changes in mitochondrial mem-brane potential (MMP) were assessed by JC-1 after cells were treated with evodiamine. The expres-sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c, Caspase-3, cleaved Caspase-3, PRAP, and cleaved PARP were measured by Western blot analy-ses. RESULTS According to MTT assay results, Evo significantly inhibited the cell proliferation in a time- and dose-dependent manner. Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disruption. Finally, Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos-phorylation(p38 and JNK,but not ERK)to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas-pase-3, and PARP). CONCLUSION In summary, Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.

Adult ; Aged ; Creatinine ; blood ; Female ; Humans ; Laparoscopy ; methods ; Lasers, Semiconductor ; therapeutic use ; Male ; Middle Aged ; Nephrectomy ; methods ; Renal Artery ; surgery ; Retrospective Studies