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工作 计划及 相关文献 介绍

工作 计划及 相关文献 介绍. 崔佳星. 从研究目标讲开去. 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

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工作 计划及 相关文献 介绍

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  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)

  9. 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

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

  11. 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

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

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

  14. 4Abx • a well-established oral antibiotic cocktail,whichreduces the number of commensal intestinal bacteria • VCM • an antibiotic that preferentially targets Gram-positive bacteria

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

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

  17. 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

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

  19. whether DCA-feeding enhances HCC development

  20. conclusion

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