Objective To evaluate the potential effects of RS504393, CC chemokine receptor (CCR) 2b and CCR1 antagonist, on LPS-induced acute lung injury (ALI) and to investigate the underlying mechanisms. Method A549 cell line was stimulated with LPS (10 μg/mL) and then treated with RS504393 (10 μg/mL) for 6 hours. ALI model was established with intranasal administration of LPS (5 mg/kg) in C57BL/6J mice. RS504393 (5 mg/kg) was administered 30 min before LPS dripped nasally. IL-8, IL-1β, plasminogen activator inhibitor (PAI)-l,monocyte chemoattractant protein (MCP)-2,and the expressions of CCR1 and CCR2b were studied by using Realtime-RT-PCR, ELISA and cyto-flowmetry. Results In A549 cell line treated with RS504393,the expressions of CCR1, CCR2b and IL-8 were significantly inhibited after LPS stimulation. In rats with LPS-induced ALI, treatment with RS504393 significantly protected mice against lung injury by attenuating influx of leukocytes and protein into bronchoalveolar space and by lessening pathological changes of lung. Treatment with RS504393 down-regulated IL-1β and PAI-1 expressions in bronchoal veolar lavage fluid (BALF) and lungs at mRNA and protein levels along with up-regulation MCP-2 expression compared to rats of vehicle-treated groups. Conclusions CCR2b and CCR1 play pivotal roles in the development of ALl,and RS504393 as a antagonist can halt the development of ALI.

Background and purpose:Overexpression of human telomerase reverse transcriptase(hTERT)plays a critical role in the process of immortalization of tumor cells.This study aims to investigate siRNA's effects on endogenous hTERT mRNA level and growth of breast cancer cells by targeting hTERT with its specific siRNA.The ultimate goal was to further elaborate the possible mechanism of immortalization in breast cancer cells.Methods:Real-Time RT-PCR was used to determine the hTERT transcripts in various breast cancer cells.hTERT siRNA was transfected into MCF7 cells with lipofectamine 2000.Cell growth was illustrated by growth curve,and cells apoptosis percentage was measured with Flow Cytometry(FACS).The relative expression levels of immortalization-related genes were evaluated with Real-Time RT-PCR.Results:Overexpressions of hTERT were demonstrated in all tested breast cancer cell lines.The inhibitory effects of hTERT siRNA were shown on both hTERT mRNA levels and cell growth from day 4 post transfection.Apoptosis was induced by hTERT siRNA as well.Certain immortalization-related genes were reduced by more than 50%,such as RAC1,PCYT2,FDFT1 and ATP5G2.Conclusions:hTERT siRNA specifically inhibited hTERT at mRNA level as well as cell growth.The apoptosis and downregulation of immortalization-related genes due to hTERT siRNA was demonstrated.

Background and purpose:The effects of triiodothyronine(T3)on breast cancer remain unclear.The aim of this study was to investigate the expression and correlation of estrogen receptor-?(ER-?)and thyroid hormone receptor-?(TR-?)in breast cancer cell lines,and to determine the changes of relevant receptors expression and its possible mechanism due to T3 treatment.Methods:Real-Time PCR was used to analyze the expressions of ER-? and TR-? at mRNA level in seven breast cancer cell lines.The expression level of retinoid X receptor-?(RXR-?)and these two receptors after T3 treatment were determined as well.The gene profile was further determined in SK-BR-3 cells treated with T3.Results:The expressions of ER-? and TR-? were quite low in SK-BR-3,MDA-MB-231 and MDA-MB-435 cells,but high in MCF7,BT20,BT474 and T47D cells.ER-?,TR-? and RXR-? were upregulated due to T3 treatment in ER-?(-)cells,but not in ER-?(+)cells.In SK-BR-3 cells,T3 treatment led to up-regulation of E2F1,TGF-?1R,TGF-?2R and hTERT,but down-regulation of TGF-?1 and p21.Conclusions:The expressions of ER-? and TR-? are correlated in breast cancer cells;the effect of T3 treatment on hormone receptors is associated with endogenous ER-? level.

Objective To investigate the effect of aquaporin 5(AQP5)gene to the differentiation and development of bone marrow-deriued dendritic cells(BMDC).Methotis The DCs obtained from the bone marrow of the AQP5-/- and the wild type(WT)mice were cultured and induced to maturation by LPS.The phenotype of the two types DCs were assayed by FACS,and the phagocytosis ability Was assayed by co-incubating with FITC-conjucted ovalbumin.Results Contrast to the DCs from the WT mice,the DCs from the A9P5-/-mice showed reducing positive rate of expression of the co-stimulating molecular such as CD40,CD80.CD86.And the phagoeytosis ability of DCs from the AOP5-/-mice was lower than that of the WT mice.The relationship of the phagncytosis rate to the time from the AOP5-/- mice was different from that of the WT mice.The stimulating ability of the AOP5-/-DCs was lower than that of the WT mice.Conclusion Water transmembrane moving mediated by AQP5 iS very important to the normal function of DCs.The certain mechanism of the signal moleeular is to be determined. Aquaporin 5;Dendritic cell;Gene knockout;Co-stimulating molecular

Objective To explore the relation between plasm neurotransmitters (Glutamic acid,GAA; γ-aminobutyric acid,GABA; 5-hydroxytryptamine,5-HT; and noradrenaline,NE) and depression in acute hemorrhagic stroke.Methods Objectives were screened from consecutive hospitalized patients with acute stroke.Fasting blood samples were taken on the day next to hospital admission,and neurotransmitters were examined by the liquid chromatography-high resolution mass spectrometry (LC-HRMS).The fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-Ⅳ) was used to diagnose depression at two weeks after onset of stroke.The modified Ranking Scale (mRS) was followed up at 1 year.Pearson test was used to analyse the correlation between serum concentration of neurotransmitters and the Hamilton Depression scale-17items (HAMD-17) score.Logistic regression was used to analyse the relation of serum concentration of neurotransmitters and depression and outcome of stroke.Results One hundred and eightyone patients were included in this study.GABA significantly decreased [6.1 (5.0-8.2) μg/L vs 8.1 (6.3-14.7) μg/L,P ＜ 0.05] in patients with depression in hemorrhagic stroke,and there was no significant difference in GAA,5-HT,or NE.GABA concentration was negatively correlated with HAMD-17 score (r =-0.131,P ＜ 0.05) ; while concentration of serum GABA rose by 1 μg/L,risk of depression in acute phase of hemorrhagic stroke was reduced by 5.6％ (OR 0.944,95％ CI 0.893-0.997).While concentration of serum GAA rose by 1 μg/L,risk of worse outcome at 1 year was raised by 0.1％,although a statistic level was on marginal status (OR 1.001,95％ CI 1.000-1.002).Conclusions In patients with depression in the acute phase of hemorrhagic stroke,there was a significant reduction in plasm GABA concentration.GABA may have a protective effect on depression in acute phase of hemorrhagic stroke.Increased concentrations of serum GAA may increase the risk of worse outcomes at 1 year after stroke.

Objective To evaluate the efficacy of Lianhua Dingchuan Tablets in bronchial asthma.Methods Fifty BALB/C mice were randomly and equally divided into control (Con) group,ovalbumin (OVA) group,dexamethasone (DEX) group,high-dose Lianhua group,low-dose Lianhua group.The mice were sensitized and challenged with OVA plus aluminium hydroxide to establish asthmatic model and were pre-treated 30 minutes before challenge.Specific airway resistance (sRaw) was used to evaluate airway hyperresponsiveness,and airway inflammatory changes were measured.ELISA and Magnetic Luminex(R) were used to quantified the levels of IL-4,IL-13 and INF-γ.Results Airway resistance significantly decreased in DEX group and High-dose Lianhua group (P＜0.05).Levels of inflammatory cells and IL-13 in BALF evidently reduced in DEX group,high-dose Lianhua group and low-dose Lianhua group (P ＜ 0.05),while IL-13 level in serum only decreased in DEX group.There was no significant changes in the levels of IL 4 and INF γ among those groups.Conclusions Lianhua Dingchuan Tablets might relieve the symptoms of asthma by reducing IL-13 level and inhibiting the airway inflammation.

Objective To investigate the effect of aspirin on oxygen glucose deprivation/reoxygen-ation(OGD/R)-induced injury in mouse hippocampal neuron HT22 cells by regulating ferropto-sis.Methods HT22 cells were randomly divided into control group,model group,low-,medium-and high-dose groups(n=3).Cellular OGD/R injury model was established in the other 4 groups except the control group.Aspirin of 100,200 and 400 μg/ml was used to treat the cells from the above 3 treatment groups,respectively.Cell viability was detected by CCK-8 assay.The contents of TNF-α,IL-1β and IL-6 were detected by ELISA.The contents of SOD,catalase,glutathione,reac-tive oxygen species(ROS),lactate dehydrogenase(LDH),Fe2+and MDA were detected by the corresponding reagent kits.Western blot analysis was performed to determine the expression of solute carrier family 7 members 11(SLC7A11),glutathione peroxidase 4(GPX4)and Acyl-CoA synthase long chain member 4(ACSL4).Results The model group had significantly lower cell vi-ability than the control group(0.49±0.07 vs 1.00±0.12,P＜0.01),but the viability of the low-,medium-and high-dose groups were higher than that of the model group(0.72±0.10 vs 0.49±0.07,P＜0.05;0.87±0.10 vs 0.49±0.07,P＜0.01;0.93±0.07 vs 0.49±0.07,P＜0.01).Compared with the control group,the contents of TNF-α,IL-1β,IL-6,ROS,LDH,Fe2 and MDA and the protein expression of ACSL4 were significantly increased,while the contents of SOD,catalase,glutathione and protein levels of SLC7A11 and GPX4 were obviously decreased in the model group(P＜0.01).Compared with model group,aspirin treatment reversed all above indicators no matter its doses(P＜0.05,P＜0.01).Conclusion Aspirin alleviates OGD/R-induced neuronal in-jury through regulating ferroptosis in mouse neuron HT22 cells in a dose-dependent manner.

Objective:To explore the application value of silent MR angiography (MRA) in imaging of brain arteriovenous malformation (BAVM) in children.Methods:A total of 20 children with BAVM confirmed by digital subtraction angiography (DSA) were retrospectively collected. All children were imaged by silent MRA and time-of-flight MRA (TOF MRA) in the same examination. The image quality of feeding artery, nidus and drainage vein of BAVM was evaluated using the four-point method. Wilcoxon rank-sum test was utilized to compare the image quality scores between silent MRA and TOF MRA. Weighted Kappa statistics used to evaluate the inter-modality agreement of silent MRA and TOF MRA with DSA in displaying of angioarchitecture characteristics and determination of Spetzler-Martin grading.Results:Among the 20 BAVMs, significant differences in image quality scores of the nidus (2.75±0.55 versus 2.20±0.70) and drainage vein (2.60±0.68 versus 2.20±0.77) were observed between silent MRA and TOF MRA ( Z=-3.05, P=0.002; Z=-2.13, P=0.033, respectively). The agreement between silent MRA and DSA was excellent in nidus size grading, deep venous drainage, associated aneurysm and SM grading (Kappa 0.91, 1.00, 0.83 and 0.93, respectively); The agreement between TOF MRA and DSA was fair to moderate (Kappa 0.46, 0.59, 0.35 and 0.47, respectively). Conclusions:Silent MRA showes better image quality compared to TOF MRA and improves the evaluation of angioarchitecture characteristics and Spetzler-Martin grading of BAVMs in children.