工作 计划及 相关文献 介绍

1. 工作计划及相关文献介绍 崔佳星

2. 从研究目标讲开去

3. 背景 • 菌群与免疫系统共生 • 抗生素的滥用，饮食结构的不合理，使微生物菌群失去恢复力和多样性，不能建立平衡免疫反应，引起自身免疫和炎症失调等。 • 菌群与癌症的关系 • Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il102/2 mice • Bacterial genotoxincolibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype • Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome

4. 目标 • 在舌苔菌群中找与肝癌发生，复发，化疗有关的biomarker • 血液中biomarker在舌苔中存在 有损->无损 • 可能会在菌群中发现特有的biomarker

5. 依据 (背景目标 ) • 肠道菌群与舌苔菌群的关系（调研） • 菌的功能 • 菌与机体的关系

6. 方法 • 多层次：舌象，舌苔，口腔上皮细胞，血液（验证），组织切片 • 动态：手术前后，化疗前后，是否复发，随访 Control：病人家属（夫妻） • 舌苔菌群与饮食结构的关系 • 复发与饮食结构的关系 菌群分析软件的学习（mothur）

7. 预期（调研） • 肿瘤类型——化疗药——术后复发、并发症——副作用出现与否及出现时间 • 舌苔颜色变化 • 舌苔菌群变化 • 什么菌能成为标志，机理是什么？（论文介绍）

8. 验证 • 老鼠验证 • 老鼠菌与人菌的区别（调研）

10. 背景 • Obesity is increasingly recognized as a major risk factor for several common types of cancer. • Cellular senescence • a process occurring in normal cells in response to telomere erosion or oncogene activation, acting through checkpoint activation and stable cell-cycle arrest as a barrier to tumorigenesis • senescence-associated secretory phenotype (SASP) • senescent cells develop a secretory profile composed mainly of inflammatory cytokines, chemokines and proteases • some of the SASP factors, such as IL-6 and PAI-1, are known to increase cancer risk in obesity

12. obesity, but not the HFD, promotes HCC development

13. P21 • senescence inducer • P21 expresses only in activated hepatic stellate cells (HSCs), which express a-smooth muscle actin (a-SMA) and desmin. • DAPI • DNA • senescence markers • a-SMA Desmin • HSCs • P16 53BP1 γ-H2AX • DNA damage • IL-6, Gro-a, CXCL9 • major components of SASP

17. SASP, but not senescence cell-cyclearrest, promotes obesity-associated HCC development

19. Alterations of intestinal microbiota are associated with obesity. • Intestinal Gram-negative bacteria has been shown to promote HCCdevelopment

21. 4Abx • a well-established oral antibiotic cocktail,whichreduces the number of commensal intestinal bacteria • VCM • an antibiotic that preferentially targets Gram-positive bacteria

22. The obesity-associated increase of Gram-positive bacteria may promote HCC development, through the enterohepatic circulation of gut bacterial metabolites or toxins.

24. Analyse serum metabolites of HFD- and normaldiet-fed mice DCA increased by the HFD feeding, reduced by antibiotic treatments

25. deoxycholic acid (DCA) • a secondary bile acid produced solely by the 7α-dehydroxylation of primary bile acids carried out by gut bacteria such as strains belonging to Clostridium cluster XI and XIVa • Cause DNA damage, which is a inducer of SASP • Been shown to enhance liver carcinogenesis

27. lower the levels of DCA, by either DFA III or UDCA Reduce HCC development

28. whether DCA-feeding enhances HCC development

29. conclusion