2-[3-((Z)-2-{4-[Bis(2-chloro-eth-yl)amino]-phen-yl}ethen-yl)-5,5-dimethyl-cyclo-hex-2-en-1-yl-idene]propane-dinitrile.

The highly conjugated title compound, C(23)H(25)Cl(2)N(3), is nearly planar (the mean deviation from the plane being 0.049 Å), except for the -C(CH(3))(2) group on the cyclo-hexene ring and the two CH(2)Cl groups. The cyclo-hexene ring has an envelope configuration. In the crystal, the packing is stabilized by C-H⋯Cl inter-actions and C-H⋯π inter-actions involving the benzene ring.

[Association between polymorphism of BDNF and internalizing disorders].

OBJECTIVE: To investigate the genetic association between brain-derived neurotrophic factor (BDNF) gene polymorphism and internalizing disorders, to provide the theoretical basis to explore the etiology of internalizing disorders. METHODS: PCR-based ligase detection reaction (PCR-LDR) was applied to tag single nucleotide lengh polymorphism (SNPs) of BDNF gene among 259 undergraduates affected by internalizing disorders and 269 healthy undergraduates. Haplotype analysis and multiple locus analysis were conducted to analyze the genotyping data. RESULTS: The genotypic frequency of tag SNPs of BDNF gene did not deviate from Hardy-Weinberg equilibrium in both case and control groups. Rs12273539 was not associated with internalizing disorders (P > 0.05), but rs10835210 and rs2030324 were related to internalizing disorders (P < 0.05). The case group had more A allele of rs10835210 and C allele of rs2030324 when compared to the controls while A allele of rs10835210 and C allele of rs2030324 seemed to be the risk factors of internalizing disorder (OR = 1.877, P < 0.001; OR = 1.347, P < 0.05). Results of multiple locus analysis showed that the haplotype composed by the three tag SNPs which was related to internalizing disorders (chi(2) = 23.537, P < 0.001). CONCLUSION: BDNF gene might serve as the susceptible gene for internalizing disorder.

[Study on the genetic association between the polymorphism of cytosolic phospholipase A2 family genes and schizophrenia].

OBJECTIVE: To investigate the genetic association between the polymorphism of cytosolic phospholipase A2 (cPLA2) family genes and schizophrenia in the North Han Chinese. METHODS: Method of polymerase chain reaction-based ligase detection reaction (PCR-LDR) was applied to genotype 10 single nucleotide polymorphisms (SNPs) of cPLA2 family genes among 201 pedigrees consisting of fathers, mothers and affected offsprings with schizophrenia. Haplotype relative risk (HRR) test, transmission disequilibrium test (TDT), haplotype transmission analysis and multiple locus analysis were conducted to analyze the genotyping data. RESULTS: The genotypic frequency of cPLA2 gene did not deviate from Hardy-Weinberg equilibrium in both case and control groups. HRR and TDT showed that the 10 SNPs were not associated with schizophrenia (P > 0.05). Analysis for haplotype transmission showed that no haplotype systems was associated with schizophrenia (P > 0.05). Results from COA and COG tests showed a disease association for the rs2162886-rs1668589, rs891014-rs1668589 and rs2307279-rs7542180 combinations (chi2 = 6.913, P = 0.032; chi2 = 8.393, P = 0.015; chi2 = 8.447, P = 0.038). CONCLUSION: Many loci in the cPLA2 family genes were associated with schizophrenic.

Is KPNB3 locus associated with schizophrenia?

OBJECTIVE: To reconfirm the association of KPNB3 with schizophrenia in Chinese population. METHODS: Two single nucleotide polymorphisms (SNPs), rs2588014 and rs626716 at the KPNB3 locus, were genotyped in 304 Chinese Han family trios consisting of fathers, mothers, and affected offsprings with schizophrenia. These 2 SNPs were detected by PCR-based restriction fragment length polymorphism (RFLP) analysis. The Hardy-Weinberg equilibrium for genotypic distributions was estimated by the goodness-of-fit test. The UNPHASED program was used to perform transmission disequilibrium test (TDT), haplotype analysis, and pair-wise measure of linkage disequilibrium (LD) between these 2 SNPs. RESULTS: The genotypic distributions of both rs2588014 and rs626716 were in the Hardy-Weinberg equilibrium (P > 0.05). The TDT revealed allelic association with rs626716 (chi2 = 9.31, P = 0.0023) but not with rs2588014 (chi2 = 3.44, P = 0.064). The global P-value was 0.0099 for 100 permutations. The haplotype analysis also showed a disease association (chi2 = 25.97, df = 3, P = 0.0000097). CONCLUSION: The present study provides further evidence in support of the KPNB3 association with schizophrenia in Chinese population.

Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells.

AIM: To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored. METHODS: [3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, plasmid transfection, reporter assay, FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells. RESULTS: C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest. During the process, the expression of p21 protein increased, while that of cyclinD1, phospho-ERK1/2 and c-myc decreased. Furthermore, the level of CDK7 was downregulated, while the transcriptional activity of PPARgamma was upregulated. Addition of GW9662, which is a PPARgamma specific antagonist, could reserve the modulation action on CDK7. CONCLUSION: Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARgamma activation. The ERK signaling pathway was involved in this process.

[Inhibiton of conjugated linoleic acid isomers on the proliferation of tumor cells].

OBJECTIVE: To study the effect of five conjugated linoleic acid isomers on the proliferation of human tumor cell AGS and Bel7402. METHODS: AGS, Bel7402 and Lovo cells incubated in vitro were used as model. The cell visibility was investigated after treatment with conjugated linoleic acid (CLA). RESULTS: All the five isomers had inhibitory ability to AGS, Bel7402 and Lovo cell proliferation, and the effect on AGS was more effective than that on Bel7402 and Lovo. The inhibitory effect was dose-dependent. CONCLUSION: The five isomers of CLA exhibited proliferation inhibitory effect on the tumor cell of AGS and Be17402.

Searching for a schizophrenia susceptibility gene in the 22q11 region.

OBJECTIVE: To investigate a genetic association for schizophrenia within chromosome 22q11 in a Chinese Han population. METHODS: The PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis was used to detect three single nucleotide polymorphisms (SNPs), rs165655 (A/G base change) and rs165815 (C/T base change) present in the ARVCF (armadillo repeat gene deletion in velocardiofacial syndrome) locus, and rs756656 (A/C base change) in the LOC128979 (expressed sequence tags, EST) locus, among 100 Chinese family trios consisting of fathers, mothers and affected offspring with schizophrenia. Genotype data were analyzed by using linkage disequilibrium (LD) methods including haplotype relative risk (HRR) analysis, transmission disequilibrium test (TDT) and haplotype transmission analysis. RESULTS: The genotype frequency distributions of three SNPs were all in Hardy-Weinberg equilibrium (P>0.05). Both the HRR and the TDT analysis showed that rs165815 was associated with schizophrenia (chi2=6.447, df=1, P=0.011 and chi2=6.313, df=1, P=0.012, respectively), whereas the other two SNPs did not show any allelic association. The haplotype transmission analysis showed a biased transmission for the rs165655-rs165815 haplotype system (chi2=17.224, df=3, P=0.0006) and for the rs756656-rs165655-rs165815 hapoltype system (chi2=20.965, df=7, P=0.0038). CONCLUSION: Either the ARVCF gene itself or a nearby locus may confer susceptibility to schizophrenia in a Chinese Han population.

[Study on single nucleotide polymorphism of beta2 adrenoceptor gene in patients with pregnancy induced hypertension of northern China].

OBJECTIVE: To study the association of single nucleotide polymorphism (SNP) at locus +46 of human beta(2)-adrenoceptor (beta(2)-AR) gene with pregnancy induced hypertension (PIH) in women from northern China. METHOD: One hundred and eight women with PIH (PIH group) and ninety seven normal pregnant women (control group) were selected. SNP at locus +46 of human beta(2)-AR was genotyped using PCR-based restriction fragment length polymorphism (RFLP) method. RESULTS: (1) The frequencies of AA, AG and GG genotypes beta(2)-AR at locus +46 were 24.1%, 25.0% and 50.9% in PIH group, respectively. They were 24.7%, 29.9%, and 45.4% in control group, respectively (P > 0.05). The frequencies of the two alleles A and G were 36.6%, 63.4% in PIH group, and 39.7% and 60.3% in control group, respectively (P > 0.05). (2) There was a significant difference in the distribution frequency of beta(2)-AR at locus +46 between mild, moderate and severe degrees of PIH (P < 0.05). CONCLUSION: It indicates that, SNP at locus +46 of beta(2)-AR gene is not associated with generation of PIH in northern China, but it has an association with the severity of PIH.

[Searching for a schizophrenia susceptibility gene in the 22q11 region].

OBJECTIVE: To investigate the genetic association for schizophrenia within the long arm region 1 band 1 of chromosome 22 (22q11) in a Han Chinese population. METHODS: Polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis was used to detect three single nucleotide polymorphism (SNPs), rs165655 (A/G base change) and rs165815 (C/T base change) present in the ARVCF (armadillo repeat gene deletion in velocardiofacial syndrome) locus, and rs756656 (A/C base change) in the LOC128979 (expressed sequence tags, EST) locus, among 100 nuclear families composed of fathers, mothers and affected offspring with schizophrenia. Genotyping data were analyzed by linkage disequilibrium methods including haplotype relative risk (HRR) analysis, transmission disequilibrium test (TDT) and haplotype transmission analysis. RESULTS: The genotype frequency distributions of three SNPs were all in Hardy-Weinberg equilibrium; Both HRR and TDT analysis showed that rs165815 was associated with schizophrenia (P < 0.05), whereas the other two SNPs did not show any allelic association. The haplotype transmission analysis showed a biased transmission for the rs165655-rs165815 haplotype system and for the rs756656-rs165655-rs165815 haplotype system (P < 0.01). CONCLUSION: Either ARVCF gene itself or a nearby locus might confer susceptibility to schizophrenia in a Han Chinese population.

Is NOTCH4 associated with schizophrenia?

The NOTCH4 locus was reported to be associated with schizophrenia in our previous study but the subsequent replication by other workers has been inconsistent. To find out possible reasons for the poor replication, the present work was undertaken to analyse four functional single nucleotide polymorphisms (SNPs) (rs367398, rs915894, rs520692 and rs422951) at the NOTCH4 locus among 141 schizophrenic family trios of Chinese Han descent. Of these four SNPs, rs520692 was the only one associated with schizophrenia (P = 0.017); the other three, however, did not show any association with the illness, including rs367398 located in the promoter region, which had shown a strong association with the illness in our previous study conducted with British samples. Although these four SNPs analysed lie within a less than 4 kb segment of genomic DNA, the pattern of linkage disequilibrium between them was unexpected. The strongest linkage disequilibrium was shown only between rs367398 and rs520692 and between rs520692 and rs422951 in both parent and patient groups. This study raises the possibility that there might be two or more disease-underlying variants at the NOTCH4 locus or at a nearby locus, and that the allelic or locus heterogeneity may be one of the possible reasons for the poor replication of the NOTCH4 finding.

Lack of a genetic association between the TNXB locus and schizophrenia in a Chinese population.

A recent study demonstrated that the tenascin X (TNXB) gene was associated with schizophrenia in a British population. To replicate the initial finding, we analysed two positive single nucleotide polymorphisms (SNPs), rs1009382 and rs204887 present at the TNXB locus, in a Chinese population by using PCR-based restriction fragment length polymorphism analysis. We recruited a total of 136 family trios consisting of fathers, mothers and affected offspring with schizophrenia. The transmission disequilibrium test did not show allelic association between these two SNPs and schizophrenia, and the rs1009382-rs204887 haplotypes were not associated with the illness either. The present results suggest that the TNXB locus does not appear to be associated with schizophrenia in the Chinese population. Because the TNXB gene is less than 100 kb away from the NOTCH4 locus that was also reported to be associated with schizophrenia, allelic and locus heterogeneity could be possible reasons for the failure to replicate the TNXB finding.

[Sphingolipid and apoptosis].

Over the last decade, considerable progress has been made in the study of sphingolipids with the development of biological techniques. Sphingolipids play important roles in diverse physiological process, including cytoskeleton migration, angiogenesis, embryonic development and signal transduction. Except for this, the lastest evidence has suggested that sphingolipids and their metabolite (ceramide, sphingosine, sphingosine 1-phosphate) can induce apoptosis in a wide variety of tumor cell lines such as LoVo HT29, Bel7402, A549, CNE2 cells. This paper is attempted to review the recent advances of investigation into the relationship between sphingolipids and apoptosis.

[Study on the genetic association between DRB3 and DRB1 loci in the human MHC region and psychotic symptoms of schizophrenia].

OBJECTIVE: The genomic region of the human major histocompatibility complex (MHC) is located in the short arm of chromosome 6 (6p). Linkage studies have shown that the 6p region may contain a gene for schizophrenia, the MHC region has thus become particularly important in searching for the schizophrenia susceptibility gene. The present study was designed to investigate the genetic association of DRB3 and DRB1 genes with psychotic symptoms of schizophrenia. METHODS: PCR-based restriction fragment length polymorphism (RFLP) analysis was applied to genotype two single nucleotide polymorphisms (SNPs) located in the DRB3 locus and in the DRB1 one in 116 Chinese Han family trios consisting of fathers, mothers and affected offspring with schizophrenia. Chi-square (chi(2)) test and haplotype-based relative risk (HRR) analysis were used on genotyping data. RESULTS: Data on HRR analysis did not show a genetic association either between the DRB3 locus and schizophrenia or between the DRB1 locus and the illness. However, the SNP rs707954, a G to T base change, present in the DRB1 locus showed strong association with idea of reference (chi(2) = 5.484, df = 1, P = 0.019), while the genotype of rs707954 showed an association with idea of reference (chi(2) = 6.771, df = 2, P = 0.034) as will as with apathy (chi(2) = 12.110, df = 4, P = 0.017). CONCLUSION: DRB1 locus seemed likely to be associated with psychotic symptoms as idea of reference and apathy. Further studies were necessary to reveal the relations between DRB1 gene or nearby locus with its susceptibility to schizophrenia.

[Effects of spirulina on serum lipids, erythrocyte membrane fluidity and vascular endothelial cells in tail-suspended rats].

OBJECTIVE: To study the changes of erythrocyte membrane fluidity, serum lipid and vascular endothelial cell caused by simulated weightlessness in rats and the beneficial effect of spirulina. METHOD: Thirty male SD rats were divided into 3 groups: free control group (group A) and two simulated weightlessness groups (groups B, C). Rats in group A and B were fed with normal forage, and the rats in group C were fed with normal forage supplemented with 5% (W/W) spirulina. Water was taken ad libitum. RESULT: Levels of serum CHO, HDL, TG, HDL-C/CHO and erythrocyte membrane fluidity decreased significantly, and number of vascular endothelial cells in plasma increased markedly in group B as compared with those in group A; The ratio of LDL-C/HDL-C, and atherosclerosis index (AI) decreased, number of vascular endothelial cells significantly lowered; level of CHO, HDL-C and value of the IDmax of plasma as well as erythrocyte membrane fluidity remarkedly increased in group C compared with those in group B. CONCLUSION: Spirulina can improve the physiological conditions of erythrocyte membrane fluidity, serum lipid and vascular endothelial cell caused by simulated weightlessness in rats.

[Effects of dietary n-3 polyunsaturated fatty acid on lipid metabolism in rats under simulated weightlessness].

Objective. To study the effect of dietary n-3 polyunsaturated fatty acid (PUFA) on the lipid metabolism of tail-suspended rats. Method. 49 male Sprague-Dawley rats were divided into five groups: tail-suspension group I, fed with 10 wt % corn oil, tail-suspension groups II, III, IV were fed with three levels of fish oil (0.5, 1.5 or 3.0 wt %; low, middle and high level of fish oil, respectively). Group V fed with 10 wt % corn oil served as normal control. Result. Viscoelasticity of cell membrane in group III was significantly higher than that of group I (P<0.01); Vascular endothelial cells (VEC) was less in group II compared to group I; Serum total cholesterol (TC) and triglyceride (TG) , serum lipoprotein were lower in groups II, III, IV compared to group I, the higher fish oil content in diet, the lower serum lipid concentration in microgravity. Conclusion. Dietary n-3 PUFA do have distinguished effect on lipid metabolism and n-3 PUFA have certain effects on prevention of atherosclerotic disease and coronary heart disease in rats.