CHRM3 is a novel prognostic factor of poor prognosis andpromotes glioblastoma progression via activation of oncogenicinvasive growth factors

Glioblastoma(GBM)is the most aggressive cancer of the brain and has a high mortality rate due to the lack of effective treatment strategy.Clarification of molecular mechanisms of GBM’s characteristic invasive growth is urgently needed to improve the poor prognosis.Single-nuclear sequencing of primary and recurrent GBM samples revealed that levels of M3 muscarinic acetylcholine receptor(CHRM3)were significantly higher in the recurrent samples than in the primary samples.Moreover,immunohistochemical staining of an array of GBM samples showed that high levels of CHRM3 correlated with poor prognosis,consistent with The Cancer Genome Atlas database.Knockdown of CHRM3 inhibited GBM cell growth and invasion.An assay of orthotopic GBM animal model in vivo indicated that inhibition of CHRM3 significantly suppressed GBM progression with prolonged survival time.Transcriptome analysis revealed that CHRM3 knockdown significantly reduced an array of classic factors involved in cancer invasive growth,including MMP1/MMP3/MMP10/MMP12 and CXCL1/CXCL5/CXCL8.Taken together,CHRM3 is a novel and vital factor of GBM progression via regulation of multiple oncogenic genes and may serve as a new biomarker for prognosis and therapy of GBM patients.

CHRM3基因与孤独症谱系障碍

孤独症谱系障碍是一类具有遗传基础的儿童发展障碍疾病。近些年,研究者们从分子病理学层面发现中枢胆碱能神经系统异常与孤独症患者认知和行为异常存在相关性。尸检研究、临床案例、动物模型研究均发现毒蕈碱型(M型)乙酰胆碱受体异常和孤独症的发生有着密切的关系。在以小鼠为模型的行为学研究中,编码毒蕈碱型乙酰胆碱受体Ⅲ亚型的CHRM3基因突变会导致小鼠出现认知障碍、刻板行为等孤独症样表现。深入了解CHRM3基因的功能将能够帮助研究者进一步解释孤独症的相关行为特征,为孤独症儿童教育方案的制定提供新的思路和方法。

白首乌对干燥综合征模型小鼠影响的实验研究

目的:观察白首乌醇提取物对干燥综合征模型小鼠颌下腺功能的影响及作用机制。方法:采用同种小鼠自身抗原免疫诱导法建立干燥综合征(SS)小鼠模型。72只SPF级C57BL/6雌性小鼠按体重分层随机分成6组:空白组,模型组,白首乌醇提物低、中、高剂量组(0.4 g·kg^(-1)、0.8 g·kg^(-1)、1.6 g·kg^(-1)),羟氯喹组(0.03 g·kg^(-1)),除空白组小鼠不造模外,其余各组小鼠造模单日同时灌胃给予相应药物,空白组和模型组小鼠灌胃等容积生理盐水,连续60天。给药期间,定期测定小鼠饮水量和唾液分泌量。实验单日小鼠取血并剖取颌下腺,ELISA法检测小鼠血清抗SSA、抗SSB抗体水平,免疫组化法检测颌下腺组织CHRM3定位表达与分布,实时荧光定量PCR和Western Blot法检测颌下腺组织CHRM3m RNA和蛋白表达水平。结果:与模型组相比,白首乌醇提物可显著升高小鼠唾液分泌量和降低饮水量,降低小鼠血清中抗SSA、抗SSB抗体水平,提示白首乌对该模型小鼠具有改善作用,并能上调小鼠颌下腺组织CHRM3 m RNA和蛋白表达量。结论:白首乌醇提物能改善SS小鼠颌下腺功能障碍,增加小鼠唾液分泌量,其机制与上调CHRM3表达,提高M受体功能相关。