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In Meishan and Landrace pigs, sex differences in the constitutive expression of hepatic cytochrome P4501A (CYP1A) subfamily enzymes were examined in terms of their mRNA, protein, and enzyme activity. All the results from the real-time RT-PCR, western blotting, and enzyme assays for CYP1A subfamily enzymes indicated that, in 5-month-old Meishan pigs, the expression levels of CYP1A1 and CYP1A2 in males were significantly low as compared with those in females. In contrast, there were no such significant sex differences in Landrace pigs. Castration of male Meishan pigs led to a female-type expression of the CYP1A subfamily enzymes, whereas no such effect was observed in male Landrace pigs after castration. In both breeds of pigs, the administration of testosterone propionate to the females and castrated males led to marked decreases in the expression levels of mRNAs and proteins in the CYP1A subfamily enzymes, and also in their enzyme activities. Furthermore, the correlation analyses between the serum testosterone level and the gene expression levels of CYP1A subfamily enzymes in different sex-matured (1-5-month-old) male pigs revealed that the clear decrease in expression levels of hepatic CYP1A subfamily enzymes occurred at concentrations of more than 33 ng/ml of serum testosterone. Incidentally, the mean concentrations of serum testosterone in 5-month-old Landrace and Meishan pigs were around 18 and 50 ng/ml respectively. In conclusion, we demonstrated for the first time that the serum testosterone level is one of the physiological factors which regulate constitutive expression of hepatic CYP1A1 and CYP1A2 in pigs.

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A honeycomb-patterned film is formed by casting a polymer solution of polystyrene and amphiphilic copolymer under humid condition. Amphiphilic copolymers stabilize condensed water droplets as temporal templates. Therefore, physical properties of the amphiphilic copolymer are important factors for stability of condensed water droplets and the structure of the honeycomb-patterned film. In order to verify the effect of the interfacial tension between water and chloroform solution of the amphiphilic copolymer, which is one of the important physical properties, amphiphilic copolymers were synthesized from hydrophobic monomer and hydrophilic monomer at various copolymerization ratios. The interfacial tension decreased with increasing the copolymerization ratio of the hydrophilic comonomer. Uniformity of micropores of the honeycomb-patterned film increased with decreasing the value of the interfacial tension. Moreover, polymer frame of honeycomb-patterned film became thinner with decreasing the value of the interfacial tension. These results indicate that the structure of honeycombpatterned film can be controlled by the interfacial tension between water and polymer solution.

BackgroundAlthough clinical trials have proved that statin can be used prophylactically against cardiovascular events, the direct effects of statin on plaque development are not well understood. We generated low‐density lipoprotein receptor knockout (LDLR −/−) pigs to study the effects of early statin administration on development of atherosclerotic plaques, especially advanced plaques.Methods and Results LDLR −/− pigs were generated by targeted deletion of exon 4 of the LDLR gene. Given a standard chow diet, LDLR −/− pigs showed atherosclerotic lesions starting at 6 months of age. When 3‐month‐old LDLR −/− pigs were fed a high‐cholesterol, high‐fat (HCHF) diet for 4 months (HCHF group), human‐like advanced coronary plaques developed. We also fed 3‐month‐old LDLR −/− pigs an HCHF diet with pitavastatin for 4 months (Statin Prophylaxis Group). Although serum cholesterol concentrations did not differ significantly between the 2 groups, intravascular ultrasound revealed 52% reduced plaque volume in statin‐treated pigs. Pathological examination revealed most lesions (87%) in the statin prophylaxis group were early‐stage lesions, versus 45% in the HCHF diet group (P<0.01). Thin‐cap fibroatheroma characterized 40% of the plaques in the HCHF diet group versus 8% in the statin prophylaxis group (P<0.01), intraplaque hemorrhage characterized 11% versus 1% (P<0.01), and calcification characterized 22% versus 1% (P<0.01).ConclusionsResults of our large animal experiment support statin prophylaxis before the occurrence of atherosclerosis. Early statin treatment appears to retard development of coronary artery atherosclerosis and ensure lesion stability. In addition, the LDLR −/− pigs we developed represent a large animal model of human‐like advanced coronary plaque suitable for translational research.