Objective To investigate whether lipopolysaccharide (LPS) can induce vascular endothelial cell growth factor (VEGF) expression in microglia regulated by hypoxia inducible factor-1α(HIF-1α). Methods The cultured BV2 cells were divided into four groups:control group, LPS (100 μg/L) simulated group, LPS (100 μg/L)+LPS antagonist (LRS, 200 μg/L) intervened group and LPS (100 μg/L)+HIF-1αinhibitors FM19G11 (10 mmol/L) intervened group. Immunofluorescence staining, Western blotting and ELISA were used to detect the expressions of VEGF and HIF-1α. Results Compared with the control group, the VEGF expression level was obvious high in LPS simulated group (P<0.05). LRS inhibited this effect of LPS (P<0.05). The HIF-1αlevel was increased in LPS simulated group at 8 h post-injury (P<0.05). FM19G11, the inhibitor of HIF-1αreduced the expression of VEGF induced by LPS (P<0.05). Conclusion LPS can up-regulate the expression of VEGF by HIF-1α.

In order to construct a novel multifunctional targeting nano-carrier based on pH-redox characteristics of tumor microenvironment,ketone bonds and disulfide bonds were bonded to the oligomeric hyaluronic acid (oHA) being sensitive to pH and the reduction environment.The chemical structure of oligomeric hyaluronic acid-8-mercaptomenthone 1,2-glycerolketal (oHMST) was characterized by 1H NMR,IR and ESI-MS.Curcuminloaded micelles were prepared by dialysis.The single factor investigation was carried out on the dosage form.Some properties,including particle size zeta potential,the morphology of micelles,and pH-sensitivity were studied.The materials were synthesized successfully.The micelles were spheric with a diameter of about 100 nm.The Zeta potential of the micelles was-(21.97 ± 1.08) mV.The in vitro test showed that oHMST carriers have good pH-sensitivity and redox-sensitivity.

ObjectiveTo explore the possible mechanisms of Shoutai Wan （寿胎丸） in treating recurrent miscarriage （RSA） from the perspective of immune tolerance under the acidic microenvironment at the maternal-fetal interface. MethodsFemale CBA/J mice were randomly divided into normal group， model group， progesterone group， and Shoutai Wan group， with 15 mice in each group. The mice in the normal group and model group were given 0.2 ml distilled water by gavage each day， the Shoutai Wan group given Shoutai Wan decoction 0.15 g/（10 g·d） by gavage， the progesterone group given progesterone tablets 0.44 mg/（10 g·d） by gavage. After gavage for 14 days， the mice were cohabited. Female CBA/J mice in the normal group were mated with male BALB/c mice at a ratio of 2∶1， and female CBA/J mice in the other groups were mated with male DBA/2 mice at a ratio of 2∶1 to establish the RSA mouse model. Vaginal smears were taken from the female mice the next morning， and the appearance of a large number of spermatozoa and the presence of a vaginal plug were considered as the first day of pregnancy. After the appearance of the plug， the mice were continued to be administered according to the previous method until the 10th day of pregnancy. On the 10th day of pregnancy， maternal-fetal interface tissues were collected from each group of mice， and lactate dehydrogenase colorimetric method was used to detect lactate （LA） content； qPCR method and Western blot method were used to detect the expression of immune-related factors interleukin-4 （IL-4）， interferon-gamma （IFN-γ）， transforming growth factor beta 1 （TGF-β1）， and forkhead box protein 3 （Foxp3） mRNA and protein； flow cytometry was used to detect the numbers of helper T lymphocyte 1 （Th1）， helper T lymphocyte 2 （Th2）， regulatory T cell （Treg）， classical macrophage （M1）， and alternative macrophage （M2）. The bivariate Pearson test was used to analyze the correlation between LA content and the numbers of Th1， Th2， Treg， M1， and M2 cells， as well as the correlation between LA content and the expression of IL-4， IFN-γ， TGF-β1， Foxp3 protein， and mRNA. ResultsOn the 10th day of pregnancy， compared with the normal group， the LA content decreased in the model group， and the expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues decreased， while the expression of IFN-γ protein and mRNA increased. The numbers of Th1 and M1 cells increased， while the numbers of Th2， Treg， and M2 cells decreased （P＜0.05 or P＜0.01）. Compared with the model group， the LA content increased in the Shoutai Wan group and progesterone group. The expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues increased， while the expression of IFN-γ protein and mRNA decreased. The numbers of Th1 and M1 cells decreased， while the numbers of Th2， Treg， and M2 cells increased （P＜0.05 or P＜0.01）. The LA content was positively correlated with the numbers of Th2， Treg， and M2 cells， and the expression of IL-4， TGF-β1， Foxp3 protein， and mRNA （P＜0.05 or P＜0.01）； the LA content was negatively correlated with the numbers of Th1， M1 cells， and the expression of IFN-γ protein and mRNA （P＜0.05 or P＜0.01）. ConclusionShoutai Wan may improve immune tolerance by regulating the expression of immune-related factors in the acidic microenvironment at the maternal-fetal interface of RSA model mice， thereby exerting its role in preventing miscarriage.