AIMTo study the synthesis and antitumour activities of some aryl-substituted pteridines.

METHODSA series of aryl-substituted pteridines were synthesized from 4, 6-diamino-5-nitrosopyrimidines by cyclization with 4-aminophenylacetonitriles. The antitumour activities were tested by MTT method.

RESULTSNine new compounds (I-III) were synthesized and their structures were characterized by EA, IR, 1HNMR and MS spectra. Compounds I-III showed antitumour activities in vitro.

CONCLUSIONCompounds I-III showed remarkable antitumour activities in vitro. No interaction was determined between the title compounds and calf thymus DNA. It indicated that these compounds possibly inhibit dihydrofolate reductase (DHFR) or other enzymes on which folic acid depends.

Adenocarcinoma ; pathology ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Humans ; KB Cells ; drug effects ; Lung Neoplasms ; pathology ; Molecular Structure ; Pteridines ; chemical synthesis ; chemistry ; pharmacology

OBJECTIVETo study the constituents from roots of Euphorbia hylonoma.

METHODColumn chromatographic techniques were used for isolation and purification of the chemical constituents and their structures were identified by spectral analysis (IR, 1H-NMR, 13C-NMR, 2D-NMR and MS).

RESULTSix compounds were isolated and elucidated as nonane (1), bis (2-ethylhexyl) phthalate (2), euphol (3), beta-sitosterol (4), acalyphol (5) and daucosterol (6) respectively.

CONCLUSIONCompounds 1, 2, 3, 5 and 6 were isolated from the plant for the first time.

Alkanes ; chemistry ; isolation & purification ; Diethylhexyl Phthalate ; chemistry ; isolation & purification ; Euphorbia ; chemistry ; Lanosterol ; analogs & derivatives ; chemistry ; isolation & purification ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Sitosterols ; chemistry ; isolation & purification ; Triterpenes ; chemistry ; isolation & purification

OBJECTIVETo evaluate the relationship between children's temperament and dental fear.

METHODS254 children(aged 4-6 years) during first dental treatment took part in the investigation. Their parents answered the Chinese preschool children's temperament scales (CPTS). The Frankl method was used to classify the degree of the children's dental fear. The K independent samples test and One-way ANOVA test were performed to find the differences of the type of temperament and the scores of temperament dimension among three groups.

RESULTSAmong the 254 children(aged 4-6 years), 104 had no fear, 80 had fear and 70 had extreme fear. The incidence of dental fear in children was 59.06%. There were no statistical differences (P > 0.05) of dental fear between boys and girls. There were statistically significant differences for the type of temperament among no fear group, fear group and extreme fear group. The scores of adaptability and quality of mood were higher in the extreme fear group and fear group than that in the no fear group. The differences in scores of adaptability and quality of mood was statistically significant between the extreme fear group and no fear group. But the scores of other seven temperament dimensions had no statistical significant differences among three groups.

CONCLUSIONChildren's dental fear is correlated to their temperaments. The tendencies of negative mood and slow adaptability should be considered that the patients were at risk of developing dental fear problem.

Child ; Child Behavior ; Child, Preschool ; Dental Anxiety ; Female ; Humans ; Male ; Temperament

OBJECTIVEThis study investigated the impact of metabolic syndrome on the development of cardio-cerebral vascular (CVD) events in a pre-hypertensive population.

METHODSThe data used in this prospective study was derived from the Kailuan study cohort (n = 101 510). Prehypertension was diagnosed in 29 968 (mean age: 50 ± 9 years and 23 744 males) individuals by the JNC VII criteria and these subjects were further classified into metabolic syndrome positive (MS+, n = 3447) and MS negative (MS-, n = 26 521) groups according to the modified 2004 Chinese Diabetes Society criteria. Subjects were followed up for 38 - 53 (mean 47 ± 5) months and first-ever CVD events were recorded. Baseline anthropometric and laboratory features were obtained by physical examination from June 2006 to October 2007 and the last follow-up day was December 31, 2010. Multivariable Cox proportional hazards regression models were used to analyze the risk factors of first-ever CVD events.

RESULTSThere were 354 CVD events during follow up. The incidences of CVD events (1.80% vs. 1.28%) and cerebral infarction (1.10% vs. 0.57%) were significantly higher in the MS+ group than in the MS- group (all P < 0.05). After adjustment for other established CVD risk factors, the hazards ratio was 1.45 (95%CI: 1.10 - 1.92) for total CVD events and 1.84 (95%CI: 1.27 - 2.67) for cerebral infarction events in MS+ group.

CONCLUSIONSIn this cohort, metabolic syndrome is linked with increased risk for CVD events.

Adult ; Cardiovascular Diseases ; etiology ; Cerebrovascular Disorders ; etiology ; Cohort Studies ; Female ; Humans ; Male ; Metabolic Syndrome ; complications ; Middle Aged ; Prehypertension ; complications ; Prospective Studies ; Risk Factors

OBJECTIVETo study the chemical constituents of hybridized Bulbus Fritillariae Ussuriensis.

METHODThe chemical constituents were isolated by silica column chromatography and their structures were identified by physical and chemical eveidences and spectral analysis (IR, 1H-NMR, 13C-NMR, 2D-NMR, MS).

RESULTSeven compounds were obtained and identified as (20S,25S)5alpha, 14alpha, 17beta-cevanine-6beta-hydroxy-3-one (hupehenirine, ZF1), (20S,25S)5alpha, 14alpha, 17beta-cevanine-3beta-hydroxy-6-one (hupehenizine, ZF2), (20R,25S)5alpha, 14alpha-cevanine-3beta,20beta-dihydroxy-6-one (peiminine, verticinone, ZF3), (20S,25S)5alpha, 14alpha, 17beta-cevanine-3beta, 6beta-dihydroxy (hupehenine, ZF4), (20R,25S)5alpha, 14alpha-cevanine-3beta, 6beta, 20beta-trihydroxy (isoverticine, ZF5), (20R,25S)5alpha, 14alpha-cevanine-3beta, 6alpha, 20beta-trihydroxy (peimine, verticine, ZF6), (20S,25S)5alpha, 14alpha, 17beta-evanine-6beta-hydroxy-3beta-O-beta-D-glucoside (hupeheninoside, ZF7).

CONCLUSIONCompounds ZF1-7 were isolated from hybridized Bulbus Fritillariae Ussuriensis for the first time.

Cevanes ; chemistry ; isolation & purification ; Fritillaria ; chemistry ; classification ; genetics ; Glucosides ; chemistry ; isolation & purification ; Hybridization, Genetic ; Molecular Structure ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; classification ; genetics

AIMTo establish a fingerprint analysis method of Fritillaria hupehensis.

METHODSfingerprint was performed by HPLC-ELSD. Hypersil ODS column was used; the mobile phase was composed of methanol (with 0.05% triethylamine) and water with gradient elution; flow rate was 1.0 mL x min(-1); recording time was 60 min; drift tube temperature was 75 degrees C; gas flow rate was 1.9 L x min(-1).

RESULTSHPLC fingerprint of Fritillaria hupehensis was obtained.

CONCLUSIONA reliable method was provided for controlling the quality of Fritillaria hupehensis.

Alkaloids ; analysis ; Cevanes ; analysis ; Chromatography, High Pressure Liquid ; methods ; Fritillaria ; chemistry ; Light ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Quality Control ; Reproducibility of Results ; Scattering, Radiation ; Sensitivity and Specificity

To search for potential drugs with potent antitussive, expectorant, antiasthmatic activities and low toxicity, a series of verticinone-bile acids salts were prepared based on the clearly elucidated antitussive, expectorant and antiasthmatic activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. The antitussive, expectorant and antiasthmatic activities of these verticinone-bile acid salts were then screened with different animal models. Ver-CA (verticinone-cholic acid salt) and Ver-CDCA (verticinone-chenodeoxycholic acid salt) showed much more potent activities than other compounds. The bioactivities of Ver-CA and Ver-CDCA are worthy to be intensively studied, and it is also deserved to pay much attention to their much more potent antitussive effects than codeine phosphate. In order to elucidate whether they have synergistic effect and attenuated toxicity, their activities will be continuously compared with single verticinone, cholic acid and chenodeoxycholic acid at the same doses on different animal models. The application of "combination principles" in traditional Chinese medicinal formulations may be a novel way in triditional Chinese medicine research and discovery.
Animals ; Anti-Asthmatic Agents ; chemistry ; pharmacology ; Antitussive Agents ; chemistry ; pharmacology ; Asthma ; prevention & control ; Bile Acids and Salts ; chemistry ; pharmacology ; Cevanes ; chemistry ; isolation & purification ; pharmacology ; Chenodeoxycholic Acid ; chemistry ; pharmacology ; Cholic Acid ; chemistry ; pharmacology ; Cough ; prevention & control ; Drug Combinations ; Drug Compounding ; methods ; Drug Synergism ; Expectorants ; chemistry ; pharmacology ; Female ; Fritillaria ; chemistry ; Guinea Pigs ; Male ; Mice ; Plants, Medicinal ; chemistry ; Random Allocation ; Snakes

The purpose of this study was to construct a recombinant conditionally replicating adenovirus (CRAd) expressing programmed cell death 5 (pdcd5). Pdcd5 gene was inserted in the E3 region of SG600-a CRAd in which the key genes for virus replication E1a and E1b were controlled under the human telomerase reverse transcriptase promoter (hTERTp) and the hypoxia response element (HRE) respectively, and with a deletion of 24 nucleotides within CR2 region of E1a. The insertion and orientation of all recombined plasmids were confirmed by restriction enzyme digestion and polymerase chain reaction (PCR). The infection efficiencies of a recombined virus carrying enhanced green fluorescent protein (EGFP) in leukemic cell lines were observed by using fluorescence microscope. The relative pdcd5 expression levels of K562 after being infected with SG611-pdcd5 were detected by real-time quantitative PCR. The results showed that the construction of SG611-pdcd5 was completed and confirmed. Pdcd5, hTERTp, HRE, skeleton and fiber11 of recombinant adenovirus SG611-pdcd5 were successfully amplified. The infection efficiencies of SG611-EGFP were all above 70% in both leukemic K562 and MEG-01 cell lines. SG611-pdcd5 expressed pdcd5 with high efficiency in leukemic cells as compared with Ad-pdcd5 or SG611 (p < 0.001). The expression level of pdcd5 increased gradually along with the increase of MOI. It is concluded that the triple-regulated adenovirus of SG611-pdcd5 containing the pro-apopro-tic gene pdcd5 has been successfully established with high pdcd5 expression level in leukemic cells, indicating that the recombinant adenovirus, SG611-pdcd5, promises further development of targeted tumor gene therapy.
Adenoviridae ; genetics ; Apoptosis Regulatory Proteins ; genetics ; Genetic Therapy ; methods ; Neoplasm Proteins ; genetics ; Oncolytic Viruses ; genetics ; Promoter Regions, Genetic ; Telomerase ; genetics

The expression levels of programmed cell death 5 (PDCD5) are down-regulated in many malignancies. SG611-pdcd5, a recombinant conditionally replicative adenovirus carrying pdcd5 gene expression cassette, can evidently kill the leukemic cells and protect selectively the normal cells. The purpose of this study was to investigate the synergistic killing effect of SG611-pdcd5 and low-dose etoposide (VP-16) on K562 cells. K562 cells were treated with different concentrations of VP-16 or different multiplicities of infection (MOI) of SG611-pdcd5. After 48 hours of incubation the cell viability was determined by using MTT assay. The results showed that the cell viability of SG611-pdcd5 (MOI = 40) plus VP-16 (0.5 µg/ml) group significantly decreased as compared with single SG611-pdcd5 (MOI = 40) treatment group or single VP-16(0.5 µg/ml) treatment group (42.00 ± 5.75% vs 59.45 ± 4.12%; 42.00 ± 5.75% vs 82.91 ± 3.41%, respectively, both p < 0.05). The synergistic killing effect of SG611-pdcd5 plus VP-16 was higher than that of PDCD5 protein plus VP-16 or that of non-replicating adenovirus carrying pdcd5 (Ad-pdcd5) plus VP-16 (both p < 0.05). The cell viability of VP-16 (4.0 µg/ml) plus SG611-pdcd5 (MOI = 40) group, VP-16 (4.0 µg/ml) plus proPDCD5 (40 µg/ml) group and VP-16 (4.0 µg/ml) plus Ad-pdcd5 (MOI = 80) group was 37.09 ± 1.89%, 52.36 ± 1.64% and 73.64 ± 4.33%, respectively. It is concluded that SG611-pdcd5 can promote K562 cell death induced by low-dose VP-16. The combination of SG611-pdcd5 and VP-16 can enhance the killing effect on leukemic cells.
Adenoviridae ; genetics ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Apoptosis Regulatory Proteins ; genetics ; Cell Survival ; Etoposide ; pharmacology ; Genetic Vectors ; Humans ; K562 Cells ; Neoplasm Proteins ; genetics

OBJECTIVETo observe the effect of Huxin Formula on expressions of the chief reverse cholesterol transport (RCT) associated genes, caveolin-1 and scavenger receptor-BI (SR-BI) in ApoE-gene knockout [ApoE (-/-)] mice.

METHODSThirty ApoE (-/-) mice of 4-6 weeks old were randomly divided into three groups (A-C). After being fed with high-fat diet for 16 weeks, they were treated with HXF (1 mL/100 g), pravachol (0.3 mg/100 g), and saline in equal volume respectively for 16 weeks successively; in addition, a blank group was set up with 10 C57BL/6J mice of 6-week old received 16-week high-fat feeding and saline treatment. Animals were sacrificed at the termination of the experiment, their paraffin sections of aortic tissue were used to measure the size of plaque, expressions of cavolin-1 and SR-BI were detected by immunological histochemical method.

RESULTSAs compared with the blank group, levels of caveolin-1 and SR-BI were increased in Groups A and B (P<0.01); but the increase in Group A was more significant than that in Group B (P<0.05). The plaque/aorta area ratio decreased significantly in Groups A and B, but showed insignificant difference between the two groups.

CONCLUSIONHXF could obviously increase the expressions of RCT associated genes, caveolin-1 and SR-BI, promote the RCT process, so as to reduce the formation of aorta atherosclerotic plaque in ApoE (-/-) mice.

Animals ; Aorta ; drug effects ; pathology ; Apolipoproteins E ; deficiency ; genetics ; Atherosclerosis ; pathology ; Biological Transport ; drug effects ; Caveolin 1 ; metabolism ; Cholesterol ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plaque, Atherosclerotic ; pathology ; Receptors, Scavenger ; metabolism