Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet.

AIMS/HYPOTHESIS: Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy. METHODS: Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating. Male rats were mated with control-diet-fed dams. After mating, the F0 dams were fed control diet with or without folate during pregnancy. RESULTS: Male, but not female offspring of HFSSD-fed founders were heavier than those of control-diet-fed counterparts (p < 0.05 and p = 0.066 in males and females, respectively). Both male and female offspring of HFSSD-fed founders were longer compared with control (p < 0.01 for both sexes). Folate treatment of the pregnant dams abolished the effect of the paternal diet on the offspring's body length (p Ë‚ 0.05). Female offspring of HFSSD-fed founders developed impaired glucose tolerance, which was restored by folate treatment of the dams during pregnancy. The beta cell density per pancreatic islet was decreased in offspring of HFSSD-fed rats (-20% in male and -15% in female F1 offspring, p Ë‚ 0.001 vs controls). Folate treatment significantly increased the beta cell density (4.3% and 3.3% after folate supplementation given to dams and founders, respectively, p Ë‚ 0.05 vs the offspring of HFSSD-fed male rats). Changes in liver connective tissue of female offspring of HFSSD-fed founders were ameliorated by treatment of dams with folate (p Ë‚ 0.01). Hepatic Ppara gene expression was upregulated in female offspring only (1.51-fold, p Ë‚ 0.05) and was restored in the female offspring by folate treatment (p Ë‚ 0.05). We observed an increase in hepatic Lcn2 and Tmcc2 expression in female offspring born to male rats exposed to an unhealthy diet during spermatogenesis before mating (p Ë‚ 0.05 vs controls). Folate treatment of the corresponding dams during pregnancy abolished this effect (p Ë‚ 0.05). Analysis of DNA methylation levels of CpG islands in the Ppara, Lcn2 and Tmcc2 promoter regions revealed that the paternal unhealthy diet induced alterations in the methylation pattern. These patterns were also affected by folate treatment. Total liver DNA methylation was increased by 1.52-fold in female offspring born to male rats on an unhealthy diet prior to mating (p Ë‚ 0.05). This effect was abolished by folate treatment during pregnancy (p Ë‚ 0.05 vs the offspring of HFSSD-fed male rats). CONCLUSIONS/INTERPRETATION: Folate treatment of pregnant dams restores effects on female offspring's glucose metabolism induced by pre-conception male founder HFSSD.

Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer.

Caudatin, a C-21 steroidal glyco-side isolated from Chinese herbs, has a long history of use for the treatment of multiple diseases, including cancers. However, the precise mechanisms of actions of caudatin in human uterine cancer cells remain unclear. In this study, we investigated the molecular mechanisms by which caudatin inhibits cell growth in human cervical carcinoma cell line (HeLa) and endometrial carcinoma cell line (HEC-1A). Treatment with caudatin promoted cell morphology change, inhibited cell proliferation, colony formation, migration and spheroid formation, and induced cell apoptosis. Our results showed that the expression of tumor necrosis factor; α-induced protein 1 (TNFAIP1) was downregulated in uterine cancer cells and tissues compared to paired adjacent non-tumor uterine tissues. Further molecular mechanism study showed that caudatin can directly regulate TNFAIP1 expression in a concentration-dependent manner and also associated with the downregulation of NF-κB and upregulation of BAX/BcL-2 ratio and caspase-3. Moreover, we found that overexpression of TNFAIP1 inhibits the growth and invasion, and induces apoptosis in uterine cancer cells through inhibition of the NF-κB pathway, suggesting that TNFAIP1 may act as a potential therapeutic target for the treatment of cancer. We found that caudatin inhibited tumorigenicity and upregulated TNFAIP1 in vivo. Taken together, caudatin impacts on cell proliferation, migration and apoptosis of uterine cancer cells by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of TNFAIP1/NF-κB signaling. Our findings provide new insights into understanding the anticancer mechanisms of caudatin in human uterine cancer therapy.

Mouse dead end 1-ß interacts with c-Jun and stimulates activator protein 1 transactivation.

Dead end 1 (DND1), important for maintaining the viability of primordial germ cells, is the first protein containing an RNA recognition motif that has been directly implicated as a heritable cause of spontaneous tumorigenesis. In the present study, c-Jun was identified through yeast two-hybrid screening of a 10.5-day old mouse embryo cDNA library as one of the proteins which interact with DND1-ß. The interaction between DND1-ß and c-Jun was demonstrated to occur by glutathione S­transferase pull­down and co-immunoprecipitation. Using confocal microscopy, DND1-ß was found to be specifically expressed in GC-1 spermatogonia cells, mainly in the nuclei. When transfected into GC-1 cells, DND1-ß and c-Jun were demonstrated to be co-localized principally in the nuclei. Furthermore, in a dual luciferase reporter assay, the transcriptional activity of activator protein 1 was demonstrated to be significantly increased by co-transfection with DND1-ß and c-Jun plasmids in GC-1 cells. The identification and confirmation of an additional protein interacting with DND1-ß facilitates the investigation of the functions and molecular mechanisms of DND1.

[Meta-analysis on the relationship between leptin receptor Gln223Arg and Pro1019Pro gene polymorphism and obesity in the Chinese population].

OBJECTIVE: To evaluate the associations between polymorphisms of LEPR Gln223Arg, LEPR Pro1019Pro and the risk on obesity. METHODS: A computerized search on literature was carried out in Wanfang, CNKI, VIP databases and CBM, PubMed, EMBASE databases to collect articles published between 1979 and 2010 concerning the associations between polymorphisms of LEPR Gln223Arg and/or LEPR Pro1019Pro and risk of obesity in the Chinese population. Odds ratios (ORs) were used to assess the strength of the association, and 95% confidence intervals (CIs) to present the precision of the estimates. Meta-analysis was performed using the STATA statistical software. RESULTS: Fifteen literature were collected for Meta-analysis by the uniform inclusion and exclusion criteria. There were 1096 obese patients and 949 controls for polymorphisms of LEPR Gln223Arg in 9 papers, together with 961 obese patients and 818 controls for polymorphisms of LEPR Pro1019Pro in 8 papers. Overall, there were significant associations between decreased risk of obesity and LEPR Gln223Arg polymorphisms (-668 A→G) (G versus A, OR = 0.66, 95%CI: 0.49 - 0.89; AG and GG versus AA, OR = 0.50, 95%CI: 0.32 - 0.77; respectively). There were significant associations between increased risk of obesity and LEPR Pro1019Pro polymorphisms (-3057 G→A) (A versus G, OR = 1.61, 95%CI: 1.15 - 2.26; AG and AA versus GG, OR = 1.50, 95%CI: 1.08 - 2.08; respectively). CONCLUSION: Variant alleles at both LEPR-668 and LEPR-3057 were associated with obesity in the Chinese Han-dominated population.

Splicing-site recognition of rice (Oryza sativa L.) DNA sequences by support vector machines.

MOTIVATION: It was found that high accuracy splicing-site recognition of rice (Oryza sativa L.) DNA sequence is especially difficult. We described a new method for the splicing-site recognition of rice DNA sequences. METHOD: Based on the intron in eukaryotic organisms conforming to the principle of GT-AG, we used support vector machines (SVM) to predict the splicing sites. By machine learning, we built a model and used it to test the effect of the test data set of true and pseudo splicing sites. RESULTS: The prediction accuracy we obtained was 87.53% at the true 5' end splicing site and 87.37% at the true 3' end splicing sites. The results suggested that the SVM approach could achieve higher accuracy than the previous approaches.

Helicobacter species ribosomal DNA recovered from the liver tissue of chinese patients with primary hepatocellular carcinoma.

Using polymerase chain reaction (PCR), we examined 16S ribosomal DNA (rDNA) of Helicobacter species in liver tissue specimens obtained from 15 patients with hepatocellular carcinoma. Sixty percent (9 of 15) of these specimens were found to be positive for Helicobacter species. Four 16S rDNA fragments from positive PCR samples were directly sequenced. By sequence comparison, all were found to be 99% identical to the 16S rRNA of Helicobacter pylori.