ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI/CLA-1) are the key proteins in reverse cholesterol transport (RCT). The high expression of ABCA1 and SR-BI/CLA-1 can decrease the danger of atherosclerosis. The purpose of the study is to find ABCA1 and CLA-1up-regulators for treating atherosclerosis by using cell-based high throughput screening models. Among 20 000 compounds screened, E0869 [1-(3, 4-dimethylphenyl)-1-oxopropan-2-yll4-((methylsulfonyl)methyl)benzoate] was found as the positive hit. The up-regulated activities of E0869 in ABCAl1-LUC and bCA-l1-LUC HepG2 cell were 160% and 175%, respectively. The EC50 values of E0869 in ABCAl1-LUC and CLA-l1-LUC HepG2 cell were 3.79 and 1.42 pμol- x ,(-1) respectively. E0869 could upregulate the mRNA and protein levels of ABCA1, SR-BI/CLA-1 and ABCGJ1genes in HepG2 and RAW264.7 cells by Real-Time Quantitative PCR and Western blotting analysis, but could not influence the expression of FAS, SREBP-l1 and CD36. Foam cell assay showed that E0869 could inhibit lipids accumulation in mouse peritoneal macrophages RAW264.7. Cholesterol efflux assay showed that E0869 could induce HDL-mediated cholesterol efflux in mouse peritoneal macrophages RAW264.7. In conclusion, E0869 could up-regulate ABCA1 and CLA-1 activity, and had good anti-atherosclerotic activity in vitro.
ATP Binding Cassette Transporter 1 ; metabolism ; Animals ; Atherosclerosis ; drug therapy ; Biological Transport ; Cholesterol ; Hep G2 Cells ; High-Throughput Screening Assays ; Humans ; Macrophages, Peritoneal ; drug effects ; Mice ; RNA, Messenger ; Scavenger Receptors, Class B ; metabolism ; Up-Regulation

In the previous study, a high-throughput screening method was established to find the antagonists of CD36. In the present study, a new compound named IMB-1680 was found using this method. The anti-atherosclerotic activities of IMB-1680 were then evaluated. Dose-dependent activities of IMB-1680 were detected by using Sf9 [hCD36] and CHO [hCD36] models. Fluorescence microscopic photography and flow cytometry were used to analyze uptake of mLDL. Foam cell test with RAW264.7 macrophages was used to examine lipid accumulation. The results showed that IMB-1680 inhibited CD36 activity with IC50 of 2.80 and 8.79 micromol x L(-1) in Sf9[hCD36] and CHO [hCD36] cells, respectively. Fluorescence microscopic photography and flow cytometry revealed that IMB-1680 could significantly reduce DiI-AcLDL uptake. Meanwhile, IMB-1680 also could reduce lipids accumulation in RAW264.7 macrophages. In all, the data indicated that IMB-1680 might be a potent effective anti-atherosclerotic leading compound.
Animals ; CD36 Antigens ; antagonists & inhibitors ; genetics ; metabolism ; CHO Cells ; Cells, Cultured ; Cricetulus ; Dose-Response Relationship, Drug ; Foam Cells ; cytology ; High-Throughput Screening Assays ; Humans ; Lipoproteins, LDL ; metabolism ; Macrophages ; cytology ; metabolism ; Mice ; Molecular Structure ; Plasmids ; Receptors, Scavenger ; antagonists & inhibitors ; Sf9 Cells ; Spodoptera ; Transfection

OBJECTIVETo study the enriching method of total flavonoid from Herba Leonuri with polyamide and macroporous resin.

METHODSeven enriching and purifying methods were compared with the yield and purity as indexes. The method of enriching with polyamide and macroporous resin was confirmed and the process of purifying was determined by orthogonal design.

RESULTD101 resin is packed by wet method, the ratio of diameter to height is 1:7. After mixed with the extract liquids, the weight of wet resin increased to 3 times of the dry resin. Evaporated the wet resin to dryness, mixed well with a little of 95% ethanol and dry polyamide powder, evaporated them to dryness again. Elute with deionized water until the effluent being colourless, then loaded it on the macroporous adsorptive resin, elute with 50% ethanol, the volume of effluents was collected to 7 times of the column volume. The purity of total flavonoids reached to 23%, while the diversion rate from raw Herba Leonuri was to 69%.

CONCLUSIONThe process is simple and convenient, and the regeneration of resin is easy, which has a good application foreground.

Absorption ; Flavonoids ; isolation & purification ; Leonurus ; chemistry ; Nylons ; chemistry ; Resins, Plant ; chemistry

Background mental imagery is a multi-componential process involving different mental operations. Objective The present study investigated the subsystems of visual mental imagery processing and their interactions. Methods: Four experimental tasks were done: (1) object, the ability to generate global mental images; (2) resolution, the ability to generate vivid,high-resolution mental images; (3) transformation,the ability to mentally rotate patterns in images, and (4) spatial imagery,spatial cognition. 91 university students (77 males, 14 females) participated in this study. Results: Object task was highly correlated with resolution task, and the same the tendency was found between transformation task and spatial task. Conclusion: The results indicate there are different subsystems of visual mental imagery and corresponding operative strategies, but with strong correlation among these processes and abilities.

AIMTo investigate the activity of RRR-alpha-tocopheryloxybutyric acid (TOB), an ether analog of RRR-alpha-tocopheryl succinate (VES), in prostate cancer cells.

METHODSVES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rv1 cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis.

RESULTSThe MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen (PSA) at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor (VDR) expression increased after the addition of TOB.

CONCLUSIONOur data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Division ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cells, Cultured ; Fibroblasts ; cytology ; drug effects ; Humans ; Kinetics ; Male ; Prostate ; cytology ; Prostatic Neoplasms ; pathology ; Vitamin E ; analogs & derivatives ; pharmacology

Objectives: . Laryngeal ultrasonography (LUS) has been suggested as an alternative diagnostic tool for unilateral vocal fold paralysis (UVFP). The present study applied LUS and quantitative laryngeal electromyography (LEMG) in female UVFP patients to investigate the pathophysiologic mechanisms of UVFP. Methods: . In this cross-sectional study, vocal fold (VF) length parameters included resting and phonating VF length measured using B-mode LUS, and color Doppler vibrating length (CDVL) measured using the color Doppler mode. Results: . Forty female patients with UVFP were enrolled, among whom 11 and 29 were assigned to the thyroarytenoid (TA) muscle+cricothyroid (CT) muscle group (with CT involvement) and the TA (without CT involvement) group, respectively. In the TA group, the turn frequency in thyroarytenoid-lateral cricoarytenoid (TA-LCA) on the paralyzed side, as observed through LEMG, correlated with the VF length during the resting phase (R=0.368, P=0.050) and CDVL values (R=0.627, P=0.000) on the paralyzed side. In the TA+CT group, the turn ratio in the CT muscle correlated with the normalized phonatory vocal length change (nPLC; R=0.621, P=0.041) on the paralyzed side. Conclusion . CDVL and nPLC are two parameters that can be utilized to predict the turn frequencies of TA-LCA in UVFP cases without CT involvement, and the turn ratio of CT in cases of UVFP with CT involvement, respectively. The findings suggest that LUS, as a noninvasive tool, can serve as an alternative method for assessing the severity of laryngeal nerve injury and offer valuable insights into the pathophysiology of UVFP.

AIMTo observe the expression of Presenilin-1 (PS-1) and production of amyloid beta-protein (Abeta) in hippocampus of female senile rats and to investigate the effect of vitamin E(VE) on preventing Alzheimer's disease after menopause.

METHODSThe animal model was established using female senile rats. Experimental groups (n=8) were respectively given different doses of VE(5 mg/kg, 15 mg/kg, 60 mg/kg) per day. The expression of PS-1 in hippocampus was detected by immunohistochemistry, the level of Abeta in hippocampus was measured by Radioimmunoassay, and neuronal ultrastructure in hippocampal DG area was observed using transmission electron microscope.

RESULTSThe expression of PS-1 in rat hippocampus of senile control group was stronger than that of adult control group. PS-1 expressed weakly in three medication groups along with augmentation of dosage. The levels of Abeta were found to correlate statistically with the expression of PS-1. The content of Abeta in VE groups was significantly decreased compared to that in senile control group (P < 0.01). There were some changes in the neuronal ultrastructure of senile rats. Neurons were gradually recovered in VE groups.

CONCLUSIONVE may depress the production of Abeta by regulating the expression of PS-1, reducing neuronal injuries. VE may play a role in neuronal protection.

Aging ; Alzheimer Disease ; metabolism ; Amyloid beta-Peptides ; metabolism ; Animals ; Female ; Hippocampus ; drug effects ; metabolism ; Presenilin-1 ; metabolism ; Rats ; Rats, Wistar ; Vitamin E ; pharmacology

OBJECTIVETo compare the schizontocidal activity of recrystallized or crude daphnetin against malaria parasites in vivo.

METHODSSchizontocidal activity of recrystallized or crude daphnetin at various dosages was assessed in mice infected with Plasmodium berghei ANKA using a "4-day suppress assay".

RESULTSThe comparison of the reduction rate of parasitemia caused by either recrystallized or crude dephnetin showed that ED(50) of crude daphnetin was 18.36 mg/kg, with 95% confidence limit of 5.96-56.54 mg/kg while ED50 of recrystallized daphnetin was 11.46 mg/kg, with 95% confidence limit of 8.63-15.22 mg/kg.

CONCLUSIONThe results indicate that the efficacy of recrystallized daphnetin is 37.6% higher than that of crude daphnetin.

Animals ; Antimalarials ; pharmacology ; Chromatography, High Pressure Liquid ; Dose-Response Relationship, Drug ; Malaria ; drug therapy ; parasitology ; Mice ; Parasitic Sensitivity Tests ; Plasmodium berghei ; drug effects ; Umbelliferones ; pharmacology

OBJECTIVETo prospectively study the relationship between risk factors and stroke incidence and mortality in the Chinese elderly.

METHODSAn analytic study in a cohort population of 1,268 male retired cadres in a military setting. A health-screening program was carried out for all cadres aged 55 years or older in Xi'an in February 1987. Baseline data on smoking, cholesterol, triglyceride, blood pressure, body mass index (BMI), histories of hypertension, hyperlipidemia and coronary heart disease (CHD), stroke, diabetes and family histories of cardiovascular disease were investigated. Main outcome measures were stroke incidence, stroke and all-cause mortality.

RESULTSThe cohort was followed up until June 30, 2001 and a total number of follow-up person-year was 15,546. During the follow-up period, there were 113 new stroke cases identified and the adjusted incidence was 727 per 100,000 person-year. Forty-five deaths were due to stroke and the adjusted mortality was 289 per 100,000 person-year. Using Cox model analysis, after adjustment on age, total cholesterol, triglyceride, smoking, drinking and physical exercise, we noticed that the systolic pressure, BMI, history of CHD and hyperlipidemia were independent risk factors for stroke incidence and morality.

CONCLUSIONThe incidence and mortality of stroke in this cohort were lower than those in the same age group of general population. Monitoring and controlling body mass index and blood pressure level seemed to be important factors for the prevention of stroke in the elderly.

Aged ; Aged, 80 and over ; Blood Pressure ; Body Mass Index ; Cohort Studies ; Coronary Disease ; complications ; Humans ; Hyperlipidemias ; complications ; Hypertension ; complications ; Incidence ; Male ; Middle Aged ; Military Personnel ; Risk Factors ; Stroke ; epidemiology ; etiology ; mortality

OBJECTIVETo detect the genes of Neisseria spp. isolated from patients with male genitourinary tract infections, and to study the pathogenicity of non-gonococcal strains of Neisseria and the laboratory diagnosis for the infections caused by Neisseria spp.

METHODSUsing polymerase chain reaction and nucleotide sequencing, we amplified and sequenced 4 genes of Neisseria spp. isolated from patients with male genitourinary tract infections, including 16S rRNA, orfl, cppB and nspA.

RESULTSFourteen Neisseria strains were identified through analysis of the 16S rRNA gene, including 3 N. mucosa strains, 3 N. cinerea strains, 2 N. gonorrhoea strains, 2 N. sicca strains, 2 N. subflava strains, 1 N. lactamica strain, and 1 N. polysaccharea strain. Among them, 9 showed positive results in gonococcal fluorescence-labeled multiplex-PCR detection, 1 in cppB gene reaction, 5 in orfl gene reaction, and 3 in nspA gene reaction. The consistency rate was 85.7% between the above results from our gene detection and those from the routine bacteriological methods.

CONCLUSIONThe cppB gene is absent in the non-gonococcal strains of Neisseria spp. that can cause male genitourinary tract infection. Most of the strains not only lack virulence-associated orfl and nspA genes, but also show positive results in gonococcal fluorescence-labeled multiplex-PCR detection, which is one of the important reasons for the misdiagnosis and missed diagnosis of gonorrhea infection. The combination of routine bacteriological methods and gene detection in laboratory examinations may help improve the accuracy rates of Neisseria species identification and clinical diagnosis of the infections caused by Neisseria spp.

Genes, Bacterial ; Gonorrhea ; diagnosis ; microbiology ; Humans ; Male ; Neisseria gonorrhoeae ; classification ; genetics ; Polymerase Chain Reaction ; Urinary Tract Infections ; microbiology