[Association of cytotoxic T lymphocyte antigen-4 gene polymorphisms with susceptibility to breast cancer].

AIM: To investigate the association between the CTLA-4 promoter-1722(T/C) and 3' untranslated region CT60(G/A) polymorphisms and the risk of breast cancer in Han women of northeast China. METHODS: 328 patients with breast cancer and 327 healthy people as control were genotyped for -1722 and CT60 polymorphism using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The frequency of the G allele at the CT60 site in breast cancer patients was statistically higher than that in control(28.7% vs 23.5%, P=0.0352, OR=1.30, 95% CI=1.02-1.67). The frequency of -1722C-CT60A haplotype in control was significantly higher than that in breast cancer patients(P=0.0283, OR=0.77, 95% CI=0.97-0.61). However, the distribution of genotypes at -1722 site was not significantly different between breast cancer patients and control. CONCLUSION: The polymorphism of -1722T/C and CT60G/A may be related to the development of breast cancer in Han women of northern China.

[Total glucosides of peony as adjuvant therapy for prevention of cardiac allograft rejection in rats].

OBJECTIVE: To evaluate the role of total glucosides of peony (TGP) as adjuvant therapy for prevention of cardiac allograft rejection in rats. METHODS: Rats with cardiac allograft were randomly divided into control group, tacrolimus-treated group, TGP-treated group and tacrolimus plus TGP-treated group. Graft survival time was observed. Allografts in some cases were examined by histological study seven days after transplantation. At the same time, the levels of CD4(+) and CD8(+) T cell subsets in peripheral blood were examined by using flow cytometry; the hepatic function and renal function of recipients were also tested. RESULTS: The graft survival time of the tacrolimus-treated group and tacrolimus plus TGP-treated group was (11.14+/-1.57) d and (13.57+/-1.99) d, respectively. The graft survival time of the tacrolimus plus TGP-treated group was longer than that of the tacrolimus-treated group (P<0.05). The histological study showed that the rejection of the tacrolimus plus TGP-treated group was slighter than that of the tacrolimus-treated group. The levels of CD4(+) T cell subset in the peripheral blood of the tacrolimus-treated and tacrolimus plus TGP-treated groups were (38.71+/-5.15)% and (32.43+/-4.39)% respectively 7 days after transplantation. The level of CD4(+) T cell subset in the tacrolimus plus TGP-treated group was lower than that in the tacrolimus-treated group (P<0.05). The level of CD8(+) T cell subset and the hepatic and renal function had no significant differences between the tacrolimus-treated group and the tacrolimus plus TGP-treated group. CONCLUSION: Effects of tacrolimus plus TGP in prevention of rejection are better than tacrolimus monotherapy in rats with cardiac allograft and without increasing side effects.

Eugenol and its structural analogs inhibit monoamine oxidase A and exhibit antidepressant-like activity.

Eugenol (1) is an active principle of Rhizoma acori graminei, a medicinal herb used in Asia for the treatment of symptoms reminiscent of Alzheimer's disease (AD). It has been shown to protect neuronal cells from the cytotoxic effect of amyloid beta peptides (Abetas) in cell cultures and exhibit antidepressant-like activity in mice. Results from this study show that eugenol inhibits monoamine oxidase A (MAOA) preferentially with a K(i)=26 microM. It also inhibits MAOB but at much higher concentrations (K(i)=211 microM). In both cases, inhibition is competitive with respect to the monoamine substrate. Survey of compounds structurally related to eugenol has identified a few that inhibit MAOs more potently. Structure activity relationship reveals structural features important for MAOA and MAOB inhibition. Molecular docking experiments were performed to help explain the SAR outcomes. Four of these compounds, two (1, 24) inhibiting MAOA selectively and the other two (19, 21) inhibiting neither MAOA nor MAOB, were tested for antidepressant-like activity using the forced swim test in mice. Results suggest a potential link between the antidepressant activity of eugenol and its MAOA inhibitory activity.

[Analysis of gene expression profile in lung adenocarcinoma, tumor adjacent tissue and fetal lung tissue].

OBJECTIVE: To investigate the gene expression profiles in lung adenocarcinoma (LA), tumor adjacent tissue (TAT) and fetal lung tissue (FLT) by cDNA microarray technique. METHODS: Total RNA from LA, TAT and FLT was extracted and purified. The cDNA was made by RT-PCR, and then labeled with Cy5 and Cy3 fluorescence as probes which were hybridized with the whole gene chips. Subsequently, the signal images were scanned by ScanArray 4000 fluorescence scanner and analyzed by Gene Pix PRO3.0. RESULTS: In 4 cases with LA and TAT, 25 genes were screened out for differences in gene expression level, among which 3 were upregulated and 22 downregulated; in FLT and TAT cases, 316 genes were screened out, among which 192 were upregulated and 124 downregulated; 16 genes were found to be differentially expressed genes in common in LA, TAT and FLT, among which 12 were upregulated and 4 downregulated. CONCLUSION: The 25 differentially expressed genes in LA and TAT may be related to occurrence and development of lung cancer, while the 316 genes in FLT and TAT may be related to fetal developmental. The 16 differentially expressed genes may be related to the initiation of lung cancer.

Synthesis of daidzin analogues as potential agents for alcohol abuse.

Daidzin, the active principle of an herbal remedy for 'alcohol addiction', has been shown to reduce alcohol consumption in all laboratory animals tested to date. Correlation studies using structural analogues of daidzin suggests that it acts by raising the monoamine oxidase (MAO)/mitochondrial aldehyde dehydrogenase (ALDH-2) activity ratio (J. Med. Chem. 2000, 43, 4169). Structure-activity relationship (SAR) studies on the 7-O-substituted analogues of daidzin have revealed structural features important for ALDH-2 and MAO inhibition (J. Med. Chem. 2001, 44, 3320). We here evaluated effects of substitutions at 2, 5, 6, 8, 3' and 4' positions of daidzin on its potencies for ALDH-2 and MAO inhibition. Results show that analogues with 4'-substituents that are small, polar and with hydrogen bonding capacities are most potent ALDH-2 inhibitors, whereas those that are non-polar and with electron withdrawing capacities are potent MAO inhibitors. Analogues with a 5-OH group are less potent ALDH-2 inhibitors but are more potent MAO inhibitors. All the 2-, 6-, 8- and 3'-substituted analogues tested so far do not inhibit ALDH-2 and/or have decreased potencies for MAO inhibition. This, together with the results obtained from previous studies, suggests that a potent antidipsotropic analogue would be a 4',7-disubstituted isoflavone. The 4'-substituent should be small, polar, and with hydrogen bonding capacities such as, -OH and -NH(2); whereas the 7-substituent should be a straight-chain alkyl with a terminal polar function such as -(CH(2))(n)-OH with 2< or =n < or =6, -(CH(2))(n)-COOH with 5< or =n < or =10, or -(CH(2))(n)-NH(2) with n > or =4.

[Inhibition of intracellular Ca(2+)-chelating agent on Hela cell apoptosis induced by HSV-1].

AIM: To explore the variation of intracellular free-Ca (2+) concentration during Hela cell apoptosis induced by HSV-1 and inhibition of Ca(2+)-chelating agent on the apoptosis. METHODS: Apoptosis of the Hela cells infected by HSV-1 was observed under scanning electron microscope (SEM) and transmission electron microscope (TEM), and the variation of intracellular free-Ca (2+) concentration, labeled with fluorescent probe was observed under fluorescence-microscope at a series of timepoints. RESULTS: The Hela cells infected by HSV-1 showed typical apoptotic morphological changes. Free-Ca (2+) concentration increased and reached peak at the 12 hours after HSV-1 infection. Characteristic morphological features of apoptosis occurred at the 24 hours after infection. This apoptosis could be inhibited by intracellular Ca(2+)-chelating agent. CONCLUSION: Intracellular free-Ca(2+) might play an important role in Hela cell apoptosis induced by HSV-1, which provides useful clues for clinical treatment of associated diseases.

[Expressions of TNF-alpha and IL-1beta in human ischemic brain tissues].

AIM: To detect the expression of TNF-alpha and IL-1beta in human cerebral ischemic tissues. METHODS: 13 cerebral specimens from patients died of cerebral infarction were divided into three groups, <2 d, 3-5 d, and >5d, according to the lasting time of infarctions. The expression of TNF-alpha and IL-1beta in the cerebral ischemic tissues were examined by immnohistochemical staining. The contralateral tissues were employed as controls. RESULTS: The expression of TNF-alpha and IL-1beta in the cerebral ischemic tissues were significant higher than those in the contralateral tissues. The focal distribution of the TNF-alpha(+) and IL-1beta(+) cells was identical with the ischemic area. The expression of IL-1beta and TNF-alpha peaked at the 3rd to 5th and 2nd day after ichemia, respectively. There were no significant difference between the ischemic and contralateral brains at the 5th day after ischemia for the expression of TNF-alpha and IL-1beta. CONCLUSION: Our results showed the expression of TNF-alpha and IL-1beta in human strok of infarction were similar to those in animal experiments. It is suggested that TNF-alpha and IL-1beta are involved in cerebral ischemic injury, which will be helpful for developing clinically a novel therapy aiming at cerebral ischemic injury.