肉鸭发酵床抗生素、重金属累积及细菌耐药性的演变特性

【目的】了解肉鸭发酵床使用过程中抗生素、各类金属元素累积特性,细菌抗生素耐受性演变特性。【方法】2011年11月至2013年7月,江苏某肉鸭发酵床养殖场饲养肉鸭期间,选取刚制作完成发酵床的鸭舍,和饲养4批次、8批次肉鸭时的鸭舍,检测发酵床中抗生素、金属元素含量,及发酵床中细菌的抗生素耐受水平。【结果】肉鸭发酵床垫料内强力霉素残留量因每批次肉鸭饲料中的使用而显著上升,氧氟沙星未现在垫料内累积。发酵床垫料饲养至8批次肉鸭时,垫料内耐受16、100μg/m L强力霉素三种可培养细菌的平均菌落数与比例为最高,而耐受8、50μg/m L氧氟沙星的平均菌落数、菌落数比例未现明显的增长趋势。发酵床使用过程中,垫料内As、Pb、Hg元素含量未显著增加,Cd元素检测量极低,Zn、Mn元素含量增加趋势明显,Cu、Cr元素累积速度缓慢。【结论】每批次使用强力霉素可在多批次肉鸭饲养后显著增加发酵床垫料中强力霉素含量,显著增强垫料中肠道菌群耐受强力霉素能力,Zn、Mn元素含量总体呈上升趋势。     

A radioisotope-nondependent high-sensitivity method for measuring the activity of glioblastoma-related O-methylguanine DNA methyltransferase

O⁶-Methylguanine DNA methyltransferase (MGMT) cancels the anticancer effect of temozolomide (drug for glioblastoma), which introduces methylation to DNA. Therefore, developing an MGMT inhibitor is a promising strategy for the treatment of this cancer. For this purpose, a sensitive detection method that does not depend on the conventional radioisotope (RI) method was developed. This was realized by a fluorescence-based method that measured the amount of cleavable restriction sites demethylated by the action of MGMT; this method was enhanced by introducing a polymerase chain reaction (PCR) amplification step. As an assay of enzyme activity, 20-fold higher sensitivity (subnanomolar) was attained compared with our and others’ fluorescence-based approaches.     

p53 Protein-mediated Regulation of Phosphoglycerate Dehydrogenase (PHGDH) Is Crucial for the Apoptotic Response upon Serine Starvation

Although p53 is frequently mutated in human cancers, about 80% of human melanomas retain wild-type p53. Here we report that PHGDH, the key metabolic enzyme that catalyzes the rate-limiting step of the serine biosynthesis pathway, is a target of p53 in human melanoma cells. p53 suppresses PHGDH expression and inhibits de novo serine biosynthesis. Notably, upon serine starvation, p53-mediated cell death is enhanced dramatically in response to Nutlin-3 treatment. Moreover, PHGDH has been found recently to be amplified frequently in human melanomas. We found that PHGDH overexpression significantly suppresses the apoptotic response, whereas RNAi-mediated knockdown of endogenous PHGDH promotes apoptosis under the same treatment. These results demonstrate an important role of p53 in regulating the serine biosynthesis pathway through suppressing PHGDH expression and reveal serine deprivation as a novel approach to sensitize p53-mediated apoptotic responses in human melanoma cells.