PPAR-γ激动剂吡格列酮对大剂量顺铂所致小鼠肠道微生态失调的影响

利用大剂量顺铂（DDP）诱导小鼠急性肾功能衰竭模型,研究吡格列酮对DDP所致小鼠肠道微生态的影响及其机制。

昆明种小鼠,依性别、体重随机分组：DDP组、DDP+吡格列酮组、对照组,每组10只。每日观察小鼠的体重、记录粪便数量等,并进行粪便涂片检查。DDP用药后3 d,分别取各组小鼠称重后乙醚麻醉,内眦静脉取血;分别取空肠、回肠末段、升结肠上段内容物进行细菌涂片检查。生化法检测血清尿素氮（BUN）、尿酸（UA）、丙二醛（MDA）的水平,并对数据进行统计学分析。

DDP用药后3 d,小鼠回肠、结肠内G⁺菌与G⁻菌比值均显著低于对照组小鼠。吡格列酮可明显增加DDP用药后小鼠回肠、结肠内G⁺菌与G⁻菌比值。DDP组小鼠外周血BUN、UA和MDA水平明显高于对照组小鼠,差异具有统计学意义;DDP+吡格列酮组小鼠其水平明显低于DDP组小鼠。

大剂量DDP可导致小鼠肠内菌群比例失衡;吡格列酮可能通过抑制小鼠体内氧化应激、进而减轻DDP所致的小鼠肾损伤和肠内菌群失衡。

     

SOX9/miR-130a/CTR1 axis modulates DDP-resistance of cervical cancer cell

Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. Copper transporter protein 1 (CTR1), a copper influx transporter required for high affinity copper (probably reduced Cu I) transport into the cell, reportedly promotes a significant fraction of DDP internalization in tumor cells. In the present study, we evaluated the function of CTR1 in the cell proliferation of cervical cancer upon DDP treatment. MicroRNAs (miRNAs) have been regarded as essential regulators of cell proliferation, apoptosis, migration, as well as chemoresistance. By using online tools, we screened for candidate miRNAs potentially regulate CTR1, among which miR-130a has been proved to promote cervical cancer cell proliferation through targeting PTEN in our previous study. In the present study, we investigated the role of miR-130a in cervical cancer chemoresistance to DDP, and confirmed the binding of miR-130a to CTR1. SOX9 also reportedly act on cancer chemoresistance. In the present study, we revealed that SOX9 inversely regulated miR-130a through direct targeting the promoter of miR-130a. Consistent with previous studies, SOX9 could affect cervical cancer chemoresistance to DDP. Taken together, we demonstrated a SOX9/miR-130a/CTR1 axis which modulated the chemoresistance of cervical cancer cell to DDP, and provided promising targets for dealing with the chemoresistance of cervical cancer.     

S1 nuclease sensitivity to cis- and trans-diamminedichloroplatinum(II) modified DNAS: influence of (G+C) content and nucleotide sequence

The sensitivity of S1 nuclease to cis- and trans-(NH3)2PtCl2 modified DNAs is examined as a function of the level of cis- and trans-(NH3)2PtCl2 bound, the % (G+C) content in DNA from different sources and the sequence dependence in poly(dG).poly(dC) and poly(dG-dC).poly(dG-dC). The extent of DNA digested increases with increasing levels of either isomer and is inversely influenced by the % (G+C) content of the DNA. However, the difference in the extent of digestion between the cis-and trans-(NH3)2PtCl2 modified DNAs at equivalent levels of bound isomer follows the order, calf-thymus greater than M. lysodeikticus greater than poly(dG-dC).poly(dG-dC). While there is virtually no difference in the digestion profiles for poly(dG-dC).poly(dG-dC) modified with the two isomers, there is a striking difference in the extent of digestion between cis- and trans-(NH3)2PtCl2 modified poly(dG).poly(dC). These results are discussed in light of the possible modes of binding for cis-(NH3)2PtCl2, previously reported findings on modified DNA and possible implications for modifications in cellular chromatin.