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Fatemeh Abedini1, Maznah Ismail1,4, Hossein Hosseinkhani2, Tengku Azmi Tengku Ibrahim1,3, Abdul Rahman Omar1,3, Pei Pei Chong4, Mohd Hair Bejo3, Abraham J Domb51Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; 2Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; 3Faculty of Veterinary Medicine, 4Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; 5Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Hebrew University-Hadassah Medical School, Jerusalem, IsraelAbstract: Liver metastasis is the main cause of mortality related to colorectal cancer. CXCR4 is necessary for the outgrowth of colon cancer micrometastases. In oncology, it has been demonstrated that several human tumors release lactate dehydrogenase (LDH) into the circulation. CXCR4 gene expression and serum LDH levels are often increased in patients with colorectal cancer. Despite technological advances in cancer therapy, five-year overall survival is still around 50%. Therefore, better treatment needs to be developed. RNA interference (RNAi) is a modern and powerful tool for inhibition of gene expression. However, the rate-limiting step in this technology is effective delivery of RNAi agents. We have investigated a novel strategy of CXCR4 siRNA therapy and its effect on serum LDH levels in a BALB/C mouse model of colorectal cancer metastasis to the liver. Hepatic metastasis was established by injecting a CT26.WT mouse colon carcinoma cell line via the tail vein. Our results demonstrated that CXCR4 siRNA/dextran-spermine nanoparticles achieved high silencing efficiency with low toxicity. Favorable localization of the nanoparticles was confirmed with CXCR4 gene expression in the liver, that was correlated with serum LDH levels. More research will be needed to determine the effect of CXCR4 silencing on serum LDH levels, which may be a useful marker for predicting liver metastasis in colorectal cancer.Keywords: colorectal cancer, CXCR4 siRNA, serum LDH, liver, dextran-spermine

The influence of stress due to rough handling (RH) on gastrointestinal tract (GIT) environmental pH, concentration of short chain fatty acids (SCFAs) and modulatory roles of two Lactobacillus strains was investigated in broiler chickens. Equal number of chicks was randomly assigned to one of the following treatment groups; (i): no handling + basal diet (control), (ii): RH and + basal diet (RH-BD), (iii): RH + basal diet supplemented with 107 CFU of each Lactobacillus strain per gram of feed (RH-BDL). Birds fed dietary Lactobacilli from day one until the end of the experiment and subjected to RH from day 1 to 21. Digesta from different GIT regions were collected at 14, 28, 35 and 42 days of age and SCFAs and pH were measured. Duodenal, ileal and cecal lactate concentrations together with cecal butyrate level were significantly (P < 0.05) decreased in RH-BD birds compared with the control and RH-BDL at 14 and 21 days of age. Acetate concentration was significantly (P < 0.05) reduced in the jejunum, ileum and cecum of both RH-BD and RH-BDL birds at 14 days of age. It can be concluded that, stressful condition over the course of the GIT microbial development, negatively affected microbial activity by reduction of the lactate, acetate (as the main substrate for butyric producing bacteria) and ultimately butyrate concentration along the GIT and particularly cecum. This adverse effect was effectively ameliorated by Lactobacillus supplementation.Key words: Gastrointestinal tract (GIT), SCFAs, Lactobacilli, stress.

Breast muscle fatty acid (FA) profile was studied in broiler chickens fed at different levels of n-6:n-3 polyunsaturated fatty acid (PUFA) ratios in 4 treatment groups; very high level of n-6:n-3 ratios (VH), high level of n-6:n-3 ratios (H), low level of n-6:n-3 ratios (L), very low level of n-6:n-3 ratios (VL) and control, respectively. All the birds were slaughtered at 42 days of age and breast muscle were collected. FA profile of breast muscles was determined by gas liquid chromatography. Increased levels of fish oil significantly (P < 0.05) increased the long chain PUFA (LC-PUFA) n-3 level, mainly because of the docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) content in the VL and L groups. n- 6: n-3 ratios were effectively changed by the experimental diets. The LC- PUFA n-3 content of the VL and L groups of the breast muscle was significantly (P < 0.05) lower than in the VH, H and control groups. In conclusion, an increase in PUFAs n-3 associated with the dietary supplementation of fish oil maybe consider as a functional approach to elevate the nutritional value of chicken meat with regards to human nutrition.Key words: Fatty acid, LC-PUFA n-3, chicken, fish oil.

The genetic diversity of 100 Malaysian native chickens was investigated using polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) for two candidate genes: inducible nitric oxide synthase (INOS) and natural resistance-associated macrophage protein 1 (NRAMP1). The two genes were selected because of their important role in chicken’s immune system. INOS and NRAMP1 PCR products were digested by AluI and SacI restriction enzymes, respectively. The restriction digests produced fragment sizes of 322 and 173 bp for INOS and 722 and 79 bp for NRAMP1 as one allele and an undigested PCR product as the other allele. Both loci were polymorph, however only INOS gene showed Hardy-Weinberg equilibrium. Average heterozygosity and the Shannon information index (I) was 0.43 and 0.62 for INOS and 0.48 and 0.68 for NRAMP1 genes, respectively. The observed polymorphism in this study shows the ability of these candidate genes in marker assisted selection and introgression programs to increase resistance to diseases in both Malaysian native and commercial chickens.Key words: Malaysian native chickens, polymorphism, inducible nitric oxide synthase (INOS), natural resistance-associated macrophage protein 1 (NRAMP1).

Base usage and dinucleotide frequency have been extensively studied in many eukaryotic organisms and bacteria, but not for viruses. In this paper, a comprehensive analysis of these aspects for infectious bursal disease virus (IBDV) was presented. The analysis of base usage indicated that all of the IBDV genes possess equivalent overall nucleotide distributions. However when the base usage at each codon positions was analysed by using cluster analysis, the VP5 open reading frame (ORF) formed a different cluster isolated from the other genes. The unusual base usage of VP5 ORF may indicate that the gene was originated by the virus "overprinting strategy", a strategy in which virus may create novel gene by utilizing the unused reading frames of its existing genes. Meanwhile, the GC content of the IBDV genes and the chicken's coding sequences was comparable; suggesting the virus imitation of the host to increase its translational efficiency. The analysis of dinucleotide frequency indicated that IBDV genome had dinucleotide bias: the frequencies of CpG and TpA were lower and the TpG was higher than the expected. Classical methylation pathway, a process where CpG converted to TpG, may explain the significant correlation between the CpG deficiency and TpG abundance. "Principal component analysis of the dinucleotide frequencies" (DF-PCA) was used to analyse the overall dinucleotide frequencies of IBDV genome. DF-PCA on the hypervariable region and polyprotein (VPX-VP4-VP3) gene showed that the very virulent IBDV (vvIBDV) was segregated from other strains; which meant vvIBDV had a unique dinucleotide pattern. In summary, the study of base usage and dinucleotide frequency had unravelled many overlooked genomic properties of the virus.