Objective To explore the effects of telmisartan on expression of peroxisome proliferators PPARs activated receptors and adiponectin receptor 2 in rats with nonalcoholic steatohepatitis (NASH).Methods Forty male SD rats were randomized into normal-diet control group (NC,n=15),high fat-diet control group (FC,n=15),and high fat-diet with telmisartan group (FT,n =10).NC group was given standard diet and the other two groups were given high-fat diet.At the end of the 12th week,5 rats which were randomly selected from both the NC and FC groups were given euglycermic hyperinsulinemia clamp to see if fat-liver model of rats with insulin resistance was successfully induced,and rat livers were removed for pathological examination to determine the extents of NASH.Afterwards,rats in the FT group was given telmisartan (5 mg/kg·d) while rats in both the NC and FC groups were given the same volume of 0.9% saline solution by intragastric gavage for another 4 weeks.After glucose infusion rates (GIRs) were obtained by the euglycermic hyperinsulinemia clamp technique at the end of the 16th week,all rats were sacrificed and the body weight was recorded,and serum lipids,aminotransferases and fasting blood glucose were measured.The mRNA expressions of peroxisome proliferator activated receptors (PPARs),adiponectin receptor-2 and angiotensin II type-1 receptor in the liver tissue were assessed by semi-quantitative reverse transcriptase polymerase chain reactions.Results The expressions of PPARα,PPARγ and AdipoR2 mRNA in the liver tissue of FC group were decreased significantly compared with the NC group (P<0.01),and the expression of AT1R mRNA of the liver tissue in FC group was increased significantly compared with NC group (P<0.01).Compared with the FC group,the expressions of PPARα,PPARγ and AdipoR2 mRNA in the FT group were increased (P<0.01).Serum aminotransferases,lipids and fasting blood glucose level in the rats of FC group were increased significantly compared with rats of the NC group (P<0.01),and serum aminotransferases,lipids and fasting blood glucose level in the rats of FT group were greatly improved compared with the FC group.Conclusions Telmisartan can improve glucose and lipid metabolism,stop weight gain,decrease liver index,and alleviate steatosis and inflammation of NASH rats by improving insulin resistance.Telmisartan may play an effective role in the protection of rat liver with NASH.

OBJECTIVEThe aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells (MSCs) with tumor cells can promote tumor angiogensis.

METHODSHuman glioma stem/progenitor cells (GSPCs) (SU3 cells) were transfected with red fluorescent protein (RFP) gene. Bone marrow mesenchymal stem cells (MSCs) were harvested from nude mice with whole-body green fluorescent protein (GFP) gene expression. Then the two kinds of cells were co-cultured in vitro. At the same time SU3-RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors. The co-cultured cells, GFP/RFP double positive (yellow) cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning confocal microscope.

RESULTSAfter five passages in vitro, MSCs maintained the proliferative activity and highly expressed CD105. CD105 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas. When MSCs were co-cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7% of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells.

CONCLUSIONCell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.

Animals ; Bone Marrow Cells ; physiology ; Cell Communication ; Cell Fusion ; Cells, Cultured ; Glioma ; Green Fluorescent Proteins ; Humans ; Luminescent Proteins ; Mesenchymal Stromal Cells ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Neoplasms ; Neovascularization, Pathologic ; Stem Cells ; Transfection ; Transplantation, Heterologous

Objective The aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells ( MSCs) with tumor cells can promote tumor angiogensis.Methods Human glioma stem/progenitor cells (GSPCs) (SU3 cells) were transfected with red fluorescent protein (RFP) gene.Bone marrow mesenchymal stem cells ( MSCs) were harvested from nude mice with whole-body green fluorescent protein (GFP) gene expression.Then the two kinds of cells were co-cultured in vitro.At the same time SU3-RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors.The co-cultured cells, GFP/RFP double positive ( yellow ) cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning confocal microscope.Results After five passages in vitro, MSCs maintained the proliferative activity and highly expressed CD105.CD105 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas.When MSCs were co -cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7%of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells.Conclu sion Cell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.

Objective The aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells ( MSCs) with tumor cells can promote tumor angiogensis.Methods Human glioma stem/progenitor cells (GSPCs) (SU3 cells) were transfected with red fluorescent protein (RFP) gene.Bone marrow mesenchymal stem cells ( MSCs) were harvested from nude mice with whole-body green fluorescent protein (GFP) gene expression.Then the two kinds of cells were co-cultured in vitro.At the same time SU3-RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors.The co-cultured cells, GFP/RFP double positive ( yellow ) cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning confocal microscope.Results After five passages in vitro, MSCs maintained the proliferative activity and highly expressed CD105.CD105 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas.When MSCs were co -cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7%of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells.Conclu sion Cell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.