Background:Ischemic stroke has been regarded as a major cause of disability and death around the world due to limited effective therapies.Accumulating evidence have shown that although microglia are polarized to an an...Background:Ischemic stroke has been regarded as a major cause of disability and death around the world due to limited effective therapies.Accumulating evidence have shown that although microglia are polarized to an anti-inflammatory M2 phenotype in the early stage of ischemia,they transform progressively into a proinflammatory M1 phenotype.Bone marrow-derived mesenchymal stem cells(BMSCs)may be used to treat ischemic injury through regulating the poststroke inflammatory response.However,the mechanism by which BMSCs can treat ischemic stroke remains unclarified.Objective:This study aimed to investigate whether BMSCs shift M1-to-M2 phenotype transformation of mi-croglia/macrophages and enhance neurogenesis in a rat transient middle cerebral artery occlusion(tMCAO)model.Methods:Ninety-minute tMCAO was applied to the rats,followed by reperfusion.BMSCs were transplanted into the rats via intravenous injection at 24 h after tMCAO.After being randomly divided into the sham group,the MCAO group,and the BMSCs group,the rats’behavior was assessed at 1,3,7,and 14 days following tM-CAO.qRT-PCR,double-immunofluorescence staining,and Western blot were performed at 3 and 14 days after tMCAO to determine M1/M2 polarization of microglia/macrophages.Neurogenesis was examined by double-immunofluorescence staining at 14 days after tMCAO.Expression of brain-derived neurotrophic factor(BDNF)was measured on the protein level by immunofluorescence staining at 3 and 14 days after tMCAO.Results:We found that BMSCs treatment promoted the recovery of neurological function after tMCAO,inhibited the expression of TNF𝛼,iNOS and CD16/32,which are markers of M1 microglia/macrophage,and enhanced the expression of IL10,TGF𝛽and CD206 that are markers of M2 microglia/macrophage.Moreover,BMSCs treatment promoted neurogenesis and M2-derived BDNF expression after tMCAO.Conclusion:It is indicated by the results that BMSCs modulate neuroinflammation and enhance neurogenesis,which could be due to transforming microglia/macrophages from the M1 polarization state towards M2 in a rat tMCAO model.展开更多
Tumor tissues contain cancer cells,other cellular and non-cellular comp onen ts.Tumor microe nvir onments consist of cancer cells and various types of stromal cells,can cer associated fibroblasts,bone marrow-derived c...Tumor tissues contain cancer cells,other cellular and non-cellular comp onen ts.Tumor microe nvir onments consist of cancer cells and various types of stromal cells,can cer associated fibroblasts,bone marrow-derived cells,en dothelial cells,and hematopoietic cells,mainly tumor-associated macrophages and tumor-infiltrating lymphocytes.Increasing recent evidence has demonstrated that alteration of tumor microenvironments is deeply implicated in tumor progression and metastasis in gastric can cer(GC)patients.Recent in vestigati ons have provided in sights into the molecular mecha ni sms of the interaction between tumor cells and tumor microenvironments.Interactions between cancer cells and their microe nvir onment with cytok ines and microRNA in extracellular vesicles,such as the exosome,can have a substa ntial impact on tumor characteristics.Alterati ons in the tumor microe nvironment may play a crucial role in facilitating the progression of tumor cells and metastasis,as well as the activation of cell signaling pathways,which are associated with GC cell proliferati on and in vasi on by genetic or epigenetic alterations.In this review,significant molecular in sights into the tumor microenvironment,which consist of cancer associated fibroblasts,bone marrow-derived cells,tumor-associated macrophages and tumor-infiltrating lymphocytes;the interactions between cancer cells and their microenvironment;and the clinical impacts of alterations of GC microenvironments will be discussed.展开更多
基金supported by the National Natural Sci-ence Foundation of China(Grant Nos.81274113,81873028,81903949)the Natural Science Foundation of Zhejiang Province(Grant No.LQ19H290004).
文摘Background:Ischemic stroke has been regarded as a major cause of disability and death around the world due to limited effective therapies.Accumulating evidence have shown that although microglia are polarized to an anti-inflammatory M2 phenotype in the early stage of ischemia,they transform progressively into a proinflammatory M1 phenotype.Bone marrow-derived mesenchymal stem cells(BMSCs)may be used to treat ischemic injury through regulating the poststroke inflammatory response.However,the mechanism by which BMSCs can treat ischemic stroke remains unclarified.Objective:This study aimed to investigate whether BMSCs shift M1-to-M2 phenotype transformation of mi-croglia/macrophages and enhance neurogenesis in a rat transient middle cerebral artery occlusion(tMCAO)model.Methods:Ninety-minute tMCAO was applied to the rats,followed by reperfusion.BMSCs were transplanted into the rats via intravenous injection at 24 h after tMCAO.After being randomly divided into the sham group,the MCAO group,and the BMSCs group,the rats’behavior was assessed at 1,3,7,and 14 days following tM-CAO.qRT-PCR,double-immunofluorescence staining,and Western blot were performed at 3 and 14 days after tMCAO to determine M1/M2 polarization of microglia/macrophages.Neurogenesis was examined by double-immunofluorescence staining at 14 days after tMCAO.Expression of brain-derived neurotrophic factor(BDNF)was measured on the protein level by immunofluorescence staining at 3 and 14 days after tMCAO.Results:We found that BMSCs treatment promoted the recovery of neurological function after tMCAO,inhibited the expression of TNF𝛼,iNOS and CD16/32,which are markers of M1 microglia/macrophage,and enhanced the expression of IL10,TGF𝛽and CD206 that are markers of M2 microglia/macrophage.Moreover,BMSCs treatment promoted neurogenesis and M2-derived BDNF expression after tMCAO.Conclusion:It is indicated by the results that BMSCs modulate neuroinflammation and enhance neurogenesis,which could be due to transforming microglia/macrophages from the M1 polarization state towards M2 in a rat tMCAO model.
文摘Tumor tissues contain cancer cells,other cellular and non-cellular comp onen ts.Tumor microe nvir onments consist of cancer cells and various types of stromal cells,can cer associated fibroblasts,bone marrow-derived cells,en dothelial cells,and hematopoietic cells,mainly tumor-associated macrophages and tumor-infiltrating lymphocytes.Increasing recent evidence has demonstrated that alteration of tumor microenvironments is deeply implicated in tumor progression and metastasis in gastric can cer(GC)patients.Recent in vestigati ons have provided in sights into the molecular mecha ni sms of the interaction between tumor cells and tumor microenvironments.Interactions between cancer cells and their microe nvir onment with cytok ines and microRNA in extracellular vesicles,such as the exosome,can have a substa ntial impact on tumor characteristics.Alterati ons in the tumor microe nvironment may play a crucial role in facilitating the progression of tumor cells and metastasis,as well as the activation of cell signaling pathways,which are associated with GC cell proliferati on and in vasi on by genetic or epigenetic alterations.In this review,significant molecular in sights into the tumor microenvironment,which consist of cancer associated fibroblasts,bone marrow-derived cells,tumor-associated macrophages and tumor-infiltrating lymphocytes;the interactions between cancer cells and their microenvironment;and the clinical impacts of alterations of GC microenvironments will be discussed.
