1.Effects of FXR gene deletion on neurobehaviors and neurotransmission systems in female mice
Qin CAO ; Fei HUANG ; Tingting WANG ; Yunyi LAN ; Hui WU ; Beibei ZHANG ; Zhibi HU ; Xiaojun WU
Chinese Pharmacological Bulletin 2015;(4):560-564
Aim To investigate how Farnesoid X re-ceptor (FXR),a nuclear hormone receptor,acts on neurological behaviors such as emotion,social behav-ior,memory and so on.Methods FXR’s function in central nervous system was evaluated by conducting a battery of behavioral tests including elevated plus maze test (EPMT),forced-swimming test (FST),social in-teraction test (SIT ), and passive avoidance test (PAT),and the contents of neurotransmitters were de-termined by the LC-MS /MS method in FXR knockout (KO)female mice and their wild-type controls.Re-sults FXR KO mice showed significantly increased immobility time in FST (P <0.01 ),and it showed in-creased tendency to enter the open arms in EMPT (P<0.01 ).The number of probing the open arms by FXR KO mice was more than that of the controls.Mo-reover,in SIT,FXR KO mice had remarkably in-creased sniffing interactions with the stranger mouse in the same cage (P <0.01 ).But in PAT,the latency for FXR KO mice to enter the dark chamber on the test day and the number of FXR KO mice to enter the dark chamber didn’t differ from those wild-type mice.In hippocampus,the contents of GABA,Glu,and NE were decreased prominently in FXR KO mice (P <0.05,P <0.05 and P <0.01 ,respectively)as well as the ratio of GABA to Glu (P <0.05).But in pre-frontal cortex,none of the neurotransmitters examined showed any difference between FXR KO mice and their controls.Conclusion FXR may be involved in main-tenance of the homeostasis of neural transmission in the central nervous system,thereby influences the emotion-al and social behavior in animals.
2.The status of homologous recombination deficiency and BRCA1/2 gene mutation in ovarian cancer patients in the Yunnan region and their clinical significance
CAI Jingjing ; LIU Xin ; LI Zhuoying ; HAN Tingting ; GUO Yinjin ; MA Luyao ; WANG Xiaoxiong ; LI Hongsheng ; LI Quan ; DU Yaqian ; LAN Yunyi ; SHEN Shaocong ; YANG Ruijiao ; WU Shunxian ; LIU Junxi ; ZHOU Yong
Chinese Journal of Cancer Biotherapy 2023;30(12):1082-1087
[摘 要] 目的:采用基于中国人群单核苷酸多态性位点开发的同源重组缺陷(HRD)检测工具评估云南地区卵巢癌患者的HRD状态和BRCA1/2基因突变频率并探讨其临床意义。方法:共纳入2021年1月至2023年5月间在云南省肿瘤医院收治的卵巢癌患者248例,HRD状态采用基因组瘢痕评分法(GSS)(主要依据拷贝数的长度、类型、位置及基因组断片)或HRD评分法(杂合性缺失、端粒等位基因失衡及大片段移位等基因组不稳定事件的总和)进行评估,当组织样本的GSS≥50分或HRD评分≥42分者或检测到有害的BRCA1/2基因突变时HRD被定义为阳性。分析患者HRD状态与临床病理特征的关系。结果:248名卵巢癌患者中70.97%的患者HRD呈阳性,其中BRCA1/2基因突变率为30.65%。Ⅲ~Ⅵ期、高级别浆液腺癌的卵巢癌患者具有更高的HRD阳性率(均P<0.01),HRD评分更高的患者其合并其他基因突变的频率也越高(P<0.05)。HRD状态与卵巢癌的病理类型、临床分期和其他基因突变均有关联(均P<0.01)。结论:云南地区卵巢癌患者HRD阳性率较高,HRD阳性的卵巢癌患者可以从聚ADP核糖聚合酶(PARP)抑制剂治疗中获得更大的收益。