Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Cisplatin (CIS) is one of the most active cytotoxic agents in current use and it has proven efficacy against various human malignancies. However, its clinical usefulness has been restricted by detrimental side effects, including nephrotoxicity and myelosuppression. The aim of the present study was to attempt to decrease the required dose of CIS, in order to minimize its side effects, and increase its capability to arrest, delay or reverse carcinogenesis. In addition, the present study aimed to ameliorate CIS-resistance in CRC cells, using the natural compound resveratrol (RSVL). RSVL (3,4', 5-trihydroxy-trans-stilbene) is a naturally occurring polyphenol present in the roots of white hellebore (Veratrum grandiflorum O. Loes) and extracted from >70 other plant species. RSVL can exert antioxidant and anti-inflammatory activities, and it has been shown to be active in the regulation of numerous cellular events associated with carcinogenesis. The present study evaluated the effects of RSVL on sensitization of both parent and CIS-resistant HCT-116 CRC cells to the action of cisplatin. The CIS was administered at a dose of 5 and 20 µg/ml, and CIS cytotoxicity, apoptosis, cell cycle and cisplatin cellular uptake were examined in the presence and absence of RSVL (15 µg/ml). RSVL treatment showed anti-proliferative effects and enhanced the cytotoxic effects of cis against the growth of both parent and CIS-resistant HCT-116 CRC cells, with a half maximal inhibitory concentration of 4.20 µg/ml and 4.72 µg/ml respectively. RSVL also induced a significant increase in the early apoptosis fraction and enhanced the subsequent apoptotic effects of CIS. The cellular uptake of CIS was significantly increased in the presence of RSVL, as compared with CIS treatment alone, and RSVL treatment sensitized the CIS-resistant HCT-116 cells. In conclusion, RSVL treatment increased the cytotoxic activity of CIS against the growth of both parent and CIS-resistant HCT-116 CRC cells.

Inbred normal SWR/J male and female mice, 8-10 weeks old and weighing 22.55-26.72 g, were used throughout the study. A total of 100 males and 100 females were used and were divided into 20 groups, 10 animals in each group. Azadirachtin of neemix-4.5, a commercial botanical pesticide derived from the neem tree, orally administered to male and female SWR/J mice at a dose level 9.0 mg/kg (1/10 LD50) for different treatment periods (2, 4, 6, 8 or 11.5 weeks) has produced signs of toxicity, mortality and changes in body and tissue weights of both sexes at almost all treated periods used in the present study. Moreover the oral administration of this dose level for 11.5 weeks has also resulted in some histopathological changes in the livers, kidneys and testes of treated animals compared with the control group, and the degree of these changes ranged from mild to severe in these organs of treated males. However, conflicting results have been reported concerning the toxicity of azadirachtin in mammalian species using different formulations of neem-based pesticides. It appears, therefore, that the toxicity produced by neemix-4.5 in the present study may be due to factors other than azadirachtin in this formulation.

Alpha-lactalbumin (a-LA) is a distinctive whey protein found in bovine milk and the milk of other mammalian species. Its main function in the lactating mammary glands is involved in lactose biosynthesis, which makes it a potential quantitative trait locus. The aim of this study is to determine the incidence of single nucleotide polymorphisms (SNPs) within the exonic and intronic portions of the caprine a-LA gene (LALBA) in native Saudi breeds (Ardi, Habsi and Harri) in relation to utility traits. Blood samples were collected from 300 animals (100 for each breed). Genomic DNA was extracted and a 268 bp fragment of the LALBA gene comprising exon 3 and its flanking area was amplified. Subsequent digestion with MvaI restriction endonuclease resulted in two different banding patterns: aLA A1 /aLA A1 and aLA A1/aLA A2 , and two allelic forms, i.e. aLA A1 and aLA A2 . Nucleotide sequencing of the designated LALBA amplicons was done and, following successful BLAST analysis, the sequences were submitted to GenBank (NCBI Accession No. KM267632, KM267633, KM267634 and KP940442). SNPs were searched within breeds of Saudi origin and homology was sought among caprine, ovine and bovine species. A C > T transition was identified within the fifth nucleotide of the silent a-LA A2 allele. Phylogenetic analysis on the basis of LALBA nucleotide sequence of Saudi goats indicated similarity with evolutionarily related sheep, while the origin of bovine species and deer was located some distance away.

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