简介：AbstractBackground:Both bone marrow mesenchymal stem cell (BM-MSC) and transforming growth factor-β1 (TGF-β1) have a strong anti-inflammatory capacity in stroke. But their relationship has not been well addressed. In this study, we investigated how intravenous BM-MSC transplantation in rats effected the expression of TGF-β1 48 h post cerebral ischemia, and we analyzed the main cells that produce TGF-β1.Methods:We used a distal middle cerebral artery occlusion (dMCAO) model in twenty Sprague-Dawley (SD) rats. The rats were randomly divided into two groups: the ischemic control group and the postischemic BM-MSC transplantation group. One hour after the dMCAO model was established, the rats were injected in the tail vein with either 1 ml saline or 1 × 106 BM-MSCs suspended in 1 ml saline. ELISAs were used to detect TGF-β1 content in the brain infarct core area, striatum and the plasma at 48 h after cerebral infarction. Immunofluorescent staining of brain tissue sections for TGF-β1, Iba-1, CD68 and NeuN was performed to determine the number and the proportion of double stained cells and to detect possible TGF-β1 producing cells in the brain tissue.Results:Forty-eight hours after ischemia, the TGF-β1 content in the infarcted area of the BM-MSC transplantation group (23.94 ± 4.48 pg/ml) was significantly lower than it was in the ischemic control group (34.18 ± 4.32 pg/ml) (F = 13.534, P = 0.006). The TGF-β1 content in the rat plasma in the BM-MSC transplantation group (75.91 ± 12.53 pg/ml) was significantly lower than it was in the ischemic control group (131.18 ± 16.07 pg/ml) (F = 36.779, P = 0.0002), suggesting that after transplantation of BM-MSCs, TGF-β1 levels in the plasma decreased, but there was no significant change in the striatum area. Immunofluorescence staining showed that the total number of nucleated cells (1037.67 ± 222.16 cells/mm2) in the infarcted area after transplantation was significantly higher than that in the ischemic control group (391.67 ± 69.50 cells/mm2) (F = 92.421, P < 0.01); the number of TGF-β1+ cells after transplantation (35.00 ± 13.66 cells/mm2) was significantly reduced in comparison to that in the ischemic control group (72.33 ± 32.08 cells/mm2) (F = 37.680, P < 0.01). The number of TGF-β1+/Iba-1+ microglia cells in the transplantation group (3.67 ± 3.17 cells/mm2) was significantly reduced in comparison to that of the ischemic control group (13.67 ± 5.52 cells/mm2) (F = 29.641, P < 0.01). The proportion of TGF-β1+/Iba-1+ microglia cells out of all Iba-1+ microglia cells after transplantation (4.38 ± 3.18%) was significantly decreased compared with that in the ischemic control group (12.81 ± 4.86%) (F = 28.125, P < 0.01).Conclusions:Iba-1+ microglia is one of the main cell types that express TGF-β1. Intravenous transplantation of BM-MSCs does not cooperate with TGF-β1+ cells in immune-regulation, but reduces the TGF-β1 content in the infarcted area and in the plasma at 48 h after cerebral infarction.

简介：AbstractObjective:This study was aimed to determine the changes in CXCR2 expression in preeclampsia placenta and its correlation with clinical parameters.Methods:Sixty-four gravidas ranging in age from 25 to 42 years referred to the obstetrics unit of the West China Second University Hospital from April 2012 to October 2012 were recruited in this case-control study; women were diagnosed and divided into early-onset preeclampsia group (n= 22), late-onset preeclampsia group (n= 22), and healthy pregnancy group (n= 20). After immunolocalized in human placenta, the levels of CXCR2 protein and messenger ribonucleic acid (mRNA) were detected by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. Correlations between placental CXCR2 protein expression with systolic blood pressure and lactate dehydrogenase (LDH) in early-onset preeclampsia were examined using Pearson or Spearman’s correlation coefficients.Results:Placental CXCR2 protein and mRNA expression in early-onset preeclampsia was significantly lower than it was in placentas from healthy pregnancy pregnancies and late-onset preeclampsia (P < 0.05). The placental CXCR2 protein expression correlated negatively with systolic blood pressure and LDH in early-onset preeclampsia (r= -0.51, P < 0.05; r=-0.43, P < 0.05).Conclusion:Significant abnormal placental CXCR2 expression in early-onset preeclampsia, and its correlations with some clinical parameters (systolic blood pressure and LDH) were discovered, suggesting that CXCR2 may play a role in the pathogenesis of early-onset preeclampsia.

简介：AbstractPurpose:Severe damage to the femoral head in patients with osteonecrosis has a high impact on morbidity. Despite early diagnosis, the treatment outcome is still unsatisfactory. This study aimed to explore the expression of vascular endothelial growth factor (VEGF) and cyclic guanine monophosphate (cGMP) serum level as the risk factors of femoral head osteonecrosis in alcohol-exposed Wistar rats.Methods:This was an experimental study using randomized post-test only control group design, with samples using 10-14 weeks Wistar male rats. Rats were then divided into 6 groups: 3 groups without intervention, and 3 groups with intervention using 40% alcohol given perorally. Each one group from intervention and control group was euthanized by the end of the week for 3 consecutive weeks. Proximal femurs were examined under microscope for osteonecrosis, immunohistochemically for VEGF, and blood serum for cGMP levels.Results:VEGF expression in the femoral head of alcohol-exposed Wistar rats was lower than those not exposed to alcohol (p < 0.005). Blood serum cGMP levels of alcohol-exposed Wistar rats were higher than those not exposed to alcohol (p < 0.005). The number of necrotic osteocytes in the femoral head of Wistar rats exposed to alcohol was greater than those not exposed to alcohol (p < 0.005). There are significant differences between VEGF, cGMP levels, and number of necrotic osteocytes in the control group and treatment at 1st, 2nd, and 3rd week (p < 0.005).Conclusions:Based on the result of this study, VEGF and cGMP may be considered as diagnostic biomarkers for alcohol-induced femoral head osteonecrosis.

简介：AbstractBackground:Non-coding RNAs have attracted considerable attention for their vital role in cancer. The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma (HCC) and reveal their regulatory mechanism in the pathophysiological process.Methods:We measured the expression of mucin 1 (MUC1) and miR-485-5p in tissues from 15 HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction and Western blot, screened for aberrantly expressed microRNAs (miRNAs) by miRNA microarrays. Bioinformatics tools were used to find the miRNA and circular RNA that regulated MUC1, which were validated by RNA immunoprecipitation assay and luciferase reporter assay. Cell counting kit-8, Transwell assays, and flow cytometry were used to conduct functional experiments. Proteins were examined by western blot and immunohistochemical staining assays. Significant differences between groups were estimated using the one-way analysis of variance. A P < 0.05 was considered statistically significant.Results:MUC1 was overexpressed in HCC tissues compared with that in paratumor tissues (normal vs. tumor, 1.007 ± 0.215 vs. 75.213 ± 18.403, t = 18.401, P < 0.001) while miR-485-5p was down-regulated (normal vs. tumor, 4.894 ± 0.684 vs. 1.586 ± 0.398, t= 16.191, P < 0.001). Inhibition of miR-485-5p promoted cell proliferation (73.33% ± 5.13% vs. 41.33% ± 3.51%, t= 8.913, P < 0.001), migration (102 ± 8 cells vs. 46 ± 8 cells, t= 8.681, P < 0.001), invasion (59 ± 7 cells vs. 28 ± 2 cells, t = 8.034, P < 0.01), and suppressed apoptosis (22.64% ± 6.97% vs. 36.33% ± 3.96%, t = 2.958, P < 0.05) of HepG2 cells with which MUC1 is knocked down. Mechanically, miR-485-5p binds to MUC1, while circHECTD1 binds to miR-485-5p, resulting in the indirect up-regulation of the MUC1 level.Conclusions:Our findings reveal that circHECTD1 facilitates HCC progression by sponging miR-485-5p to up-regulate MUC1.

简介：AbstractObjective:To investigate whether peroxisome proliferator-activated receptor γ (PPARγ) agonists, rosiglitazone and GW1929, activate the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B pathway and the mitogen-activated protein kinase (MAPK) /extracellular signal-regulated kinase1/2 (ERK1/2) pathway by upgrading the expression of chemerin.Methods:The HTR-8/SVneo trophoblastic cells were cultured in vitro in high glucose concentration (25 mmol/L) to mimic gestational diabetic phenotypes. We transfected small interfering RNA into HTR-8/SVneo cells to silence two receptors of chemerin, that are chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor1 (GPR1). And recombinant human chemerin, PPARγ agonists (rosiglitazone, 10 μmol/L and GW1929, 10 μmol/L) and PPARγ inhibitor (GW9662, 5 μmol/L) were additionally added to the medium, respectively. The existence of chemerin was verified by immunocytochemistry, and the expressions of PPARγ, chemerin, and its receptors as well as insulin signaling-related factors PI3K, AKT2, and MAPK (ERK1/2) were detected by real time quantitative-polymerase chain reaction and western blot.Results:Chemerin existed in the HTR-8/SVneo cells. Effects of chemerin on PI3K-AKT pathway and MAPK (ERK1/2) pathway were dependent on the density of chemerin. When rosiglitazone and GW1929 were added to the medium, the mRNA levels of PI3K, AKT2, and MAPK1 were upregulated (P < 0.05). Conversely, GW9662 downregulated the mRNA levels of AKT2 and MAPK1 (P < 0.05). Rosiglitazone and GW1929 increased the protein levels of PPARγ, chemerin, CMKLR1 and GPR1 (P < 0.05). Rosiglitazone and GW1929 had no effect on the expression of PI3K p110β and phospho-AKT2 without CMKLR1 (P > 0.05). Meanwhile, the expression of phospho-ERK2 remained unaffected in the absence of GPR1 (P > 0.05).Conclusion:Both rosiglitazone and GW1929 have the effect of improving insulin signaling pathways via upgrading the level of chemerin in high glucose treated HTR-8/SVneo cells.