| 4 | Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity显示文摘Neutrophils are derived from bone marrow hematopoietic stem cells(HSCs)and are the largest population among circulating white blood cells in humans,acting as the first line of defense against invading pathogens.Whether neutrophils can be generated by transdifferentiation strategies is unknown.Here,we show that thymidine induces the conversion of mouse fibroblasts to neutrophils.Induced neutrophils(iNeus)showed antibacterial effects and did not undergo malignant transformation in vivo.Importantly,iNeu transplantation cured neutropenia in mice in vivo.Mechanistically,thymidine mediates iNeu conversion by enhancing Tet3 activity.Tet3 initiates the expression of the neutrophil fate decision factors Cebpδ and Rfx1 that drive the transdifferentiation of mouse fibroblasts to neutrophils.Therefore,the induction of functional neutrophils by chemicals may provide a potential therapeutic strategy for patients with neutropenia patients and infectious diseases. | Buqing Ye Liuliu Yang Benyu Liu Nian Liu Dongdong Fan Huimu Li Lei Sun Ying Du Shuo Wang Yong Tian Zusen Fan | 2022 | Cellular & Molecular Immunology2022,19,5: | 0 |
| 5 | Gut liver brain axis in diseases:the implications for therapeutic interventions显示文摘Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract,liver,and nervous systems.In the past few decades,breakthrough progress has been made in the gut liver brain axis,mainly through understanding its formation mechanism and increasing treatment strategies.In this review,we discuss various complex networks including barrier permeability,gut hormones,gut microbial metabolites,vagus nerve,neurotransmitters,immunity,brain toxic metabolites,β-amyloid(Aβ)metabolism,and epigenetic regulation in the gut-liver-brain axis.Some therapies containing antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation(FMT),polyphenols,low FODMAP diet and nanotechnology application regulate the gut liver brain axis.Besides,some special treatments targeting gut-liver axis include farnesoid X receptor(FXR)agonists,takeda G protein-coupled receptor 5(TGR5)agonists,glucagon-like peptide-1(GLP-1)receptor antagonists and fibroblast growth factor 19(FGF19)analogs.Targeting gut-brain axis embraces cognitive behavioral therapy(CBT),antidepressants and tryptophan metabolism-related therapies.Targeting liver-brain axis contains epigenetic regulation and Aβmetabolism-related therapies.In the future,a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases. | Mengyao Yan Shuli Man Benyue Sun Long Ma Lanping Guo Luqi Huang Wenyuan Gao | 2024 | Signal Transduction and Targeted Therapy2024,9,1: | 0 |