Evodiamine (EVO), an indole alkaloid derived from Rutaceae plants Evodia rutaecarpa (Juss.) Benth.、Evodia rutaecarpa (Juss.) Benth. Var. bodinieri (Dode) Huang or Evodia rutaecarpa (Juss.) Benth. Var. officinalis (Dode) Huang, has anti-inflammatory and anti-tumor activities. Our previous study found that EVO attenuates colitis by regulating gut microbiota and metabolites. However, little is known about its effect on colitis-associated cancer (CAC). In this study, the protective effects of EVO on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis and tumor mice were observed, and the underlying potential mechanism was clarified. The results suggested that EVO ameliorated AOM/DSS-induced colitis by inhibiting the intestinal inflammation and improving mucosal barrier function. And EVO significantly reduced the number and size of AOM/DSS-induced colorectal tumors along with promoted apoptosis and inhibited proliferation of epithelial cell. Moreover, EVO promoted the enrichment of SCFAs-producing bacteria and reduced the levels of the pro-inflammatory bacteria, which contributes to the changes of microbiota metabolism, especially tryptophan metabolism. Furthermore, inflammatory response (like Wnt signaling pathway、Hippo signaling pathway and IL-17 signaling pathway) were effectively alleviated by EVO. Our study demonstrated that the protective therapeutic action of EVO on CAC is to inhibit the development of intestinal inflammation-cancer by regulating gut microbiota metabolites and signaling pathways of colon intestinal epithelial, which may represent a novel agent for colon cancer prevention via manipulation of gut microbiota.
Degeneration of the intervertebral disc (IVD) is a major spinal disorder that causes back pain. Nucleus pulposus (NP) in the central of IVD dehydrates and become more fibrous in the IVD degeneration. NP cells undergo apoptosis with the degeneration of extracellular matrix (ECM) components. To replenish the NP cells and core ECM, bone marrow mesenchymal stromal cells (BMSCs) have been highlighted in the regeneration of IVD degeneration. BMSCs differentiate into NP-like cells with the secretion of ECM components, which may not only replenish the number of NP cells but also stimulate NP reconstruction. This further maintains tissue homeostasis. Up to date, the disc progenitor cells (DPCs) have been identified with the characteristics of multidifferentiation and stem cell phenotype. These cells are involved in the IVD diseases and show regenerative potentials. However, the differences between the BMSCs and DPCs remain elusive, in particular, the cellular connection in vivo. As such, this chapter will discuss the findings of the two cell types and propose a novel concept in the understanding of the biology of IVD.
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