Alteration of the p53 gene during tree shrews' hepatocarcinogenesis

OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB_1; group B, only infected with HBV; group C, fed with AFB_1 alone; and group D normal control. The tree shrews underwent liver biopsy every. 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies. RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0±16.6 wk vs 153.3±5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in group D (10%) (X^2≥5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C. The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13. Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% in homology, compared with those of human p53, respectively. CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB_1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB_1 may synergistically induce p53 gene mutation.

Systematic study of(MoTa)_(x)NbTiZr medium-and high-entropy alloys for biomedical implants-In vivo biocompatibility examination

In this study,the application of medium-and high-entropy(Mo Ta)_(x)Nb Ti Zr alloys in biomedical implants was systematically analyzed.The alloy with the best combination of mechanical properties was selected and characterized for in vitro and in vivo response for the first time to examine its biomedical properties.A logarithmic increase in the hardness and the yield strength was observed as a function of the Mo and Ta content.Alloys with up to 0.4 mol fraction of Mo and Ta showed a plastic strain of more than 30%under compression.The nanoindentation results showed that the addition of Mo and Ta increased the elastic modulus of the system linearly.It was surmised that the addition of Ta and Mo above a critical concentration(mole fraction=0.4)was unfavorable from a biomedical perspective as it increased the brittleness and elastic modulus and decreased the ductility of the system.Therefore,the(Mo Ta)_(0.2)Nb Ti Zr alloy is a potential structural material for biomedical implants because of its excellent strength and ductility.The developed alloy was investigated for its corrosion properties and compared with commercial biomedical alloys.Furthermore,the biocompatibility of the alloy was examined using an in vivo examination.The alloy was implanted in the skeletal muscles of mice for four weeks and the histology of the surrounding tissue was studied.The alloy exhibited strong passive behavior in a phosphate buffer solution and non-toxic soft tissue response.