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Objective To explore the pattern of early expression and secretion of tissue factor(TF)in vascular endothelial cells induced by heat stress.Methods Thirty SPF-rated C57BL/6 male mice were randomly divided into five groups:the control group and groups of indicated recovery time,including 0,3,6,and 9 h in room temperature after heat stress(n=6).Mice in the heat stress groups were exposed to an animal incubator to reach 42.5℃for core body temperature for heat stroke.We analyzed the histopathological changes in the liver,lung,and kidney tissues with HE staining.We measured the TF mRNA in mice tissues by RT-qPCR and the plasma concentration of TF in mice with a commercial ELISA kit.Human umbilical vein endothelial cells(HUVECs)were placed in a culture incubator to build an in vitro heat stress model.HUVECs were divided into five groups,including a control group and groups of indicated recovery time,including 0,3,6,and 9 h after heat stress.We quantified the expression of TF mRNA and protein in HUVEC cells by RT-qPCR,Western blotting,and immunofluorescence and measured the secreted TF with a commercial ELISA kit.Results No significant pathological injury was observed in the tissues of the control group.Mice treated with heat stress had various degrees of structural injuries and hemorrhagic and inflammatory changes in multiple tissues.Compared to control group,the expression of TF mRNA significantly increased in the kidney of heat stress-treated mice with 0 and 3 h recovery time(1.719±0.018,1.241±0.178 vs.1.000±0.063),the lung with 3 h recovery time(2.444±0.511 vs.1.000±0.106)and the liver with 6 h recovery time(7.312±0.618 vs.1.000±0.147)(P<0.05).The concentration of TF in plasma also sustainedly elevated in mice with 0,3,6,and 9 h recovery time after heat stress as compared to control group[(132.426±17.920)pg/ml,(119.400±10.267)pg/ml,(107.374±13.495)pg/ml,(163.767±22.810)pg/ml vs.(75.479±13.831)pg/ml,respectively,P<0.01].The expression levels of TF mRNA were higher in heat stress HUVECs with 6 h and 9 h recovery time than the control cells(1.905±0.354,2.564±0.297 vs.1.000±0.097,P<0.01).Secreted TF in the supernatant from HUVECs treated with heat stress and different recovery time also increased significantly[(36.309±4.101)pg/ml,(38.425±5.484)pg/ml,(41.655±4.380)pg/ml,(43.586±4.718)pg/ml vs.(14.996±0.254)pg/ml,P<0.01].Conclusion Heat stress increased early expression and secretion of TF in vascular endothelial cells.Vascular endothelial cells may be a main source of circulating TF in heat stroke.
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<p><b>AIM</b>To synthesize oxazolindinone derivatives and test their antibacterial activities.</p><p><b>METHODS</b>3-Halo-4-methylaniline was acylated with benzyl chloroformate, followed by cyclization with (R)-glycidyl butyrate, acylation with methanesulfonyl chloride, substitution with NaN3, reduction with H2 + Pd/C or P(OMe)3 + HCl, acylation with Ac2O, and bromination with NBS to form bromides VIIIa and VIIIb, Substitution of the bromides with various amines including aliphatic amine and aromatic amine provided the target compounds IXa and IXb. The in vitro antibacterial activity of the target compounds was tested.</p><p><b>RESULTS</b>Fifty one new compounds were designed and synthesized. And their structures were confirmed by 1H NMR and elemental analyses or MS. Some physical constants such as [alpha]D25 were reported also. Compounds VIIb, IXa1, IXa2, IXa7, IXb1, IXb3, IXb10, IXb16 and IXb23 had moderate in vitro antibacterial activity against G+ bacteria but they were less active than linezolid or norfloxacin.</p><p><b>CONCLUSION</b>Insertion of methylene group between 4-position of phenyl and morpholinyl group in linezolid derivatives can not increase the antibacterial activity.</p>