This study is to investigate the effect of fenofibrate on angiotensin II (Ang II)-induced toll-like receptor 4 (TLR4) expression, myeloperoxidase (MPO) activity and expression in murine macrophage line RAW264.7 cells and explore its anti-inflammatory mechanism. TLR4 and MPO mRNA levels were analyzed by RT-PCR, and TLR4 and MPO protein expressions were measured by Western blotting. MPO activity in the cell supernatant was assayed with colorimetry. The results showed that fenofibrate reduced Ang II-induced mRNA and protein expression of TLR4 and inhibited activity, mRNA and protein expression of MPO in RAW264.7 cells in concentration-dependent manner. In addition, TLR4 blocker partially antagonized the effect of Ang II on MPO activity in RAW264.7 cells, and fenofibrate potentiated the inhibitory effect. Meanwhile, fenofibrate significantly suppressed LPS (TLR4 special ligand)-induced MPO activity in RAW264.7 cells. In conclusion, fenofibrate downregulated Ang II-induced TLR4 expression and blocked MPO secretion in RAW264.7 cells via interfering with the TLR4-dependent signaling pathway to alleviate inflammation, which might be one of its novel anti-inflammatory mechanisms.
Angiotensin II ; pharmacology ; Animals ; Anti-Inflammatory Agents ; administration & dosage ; pharmacology ; Cell Line ; Dose-Response Relationship, Drug ; Fenofibrate ; administration & dosage ; pharmacology ; Hypolipidemic Agents ; administration & dosage ; pharmacology ; Lipopolysaccharides ; pharmacology ; Macrophages ; cytology ; metabolism ; Mice ; Peroxidase ; metabolism ; RNA, Messenger ; metabolism ; Signal Transduction ; Toll-Like Receptor 4 ; antagonists & inhibitors ; metabolism

OBJECTIVETo investigate the effect of rosiglitazone on angiotensin II (Ang II)-induced mRNA and protein expressions of toll-like receptor 4 (TLR4) and myeloperoxidase (MPO) activity in RAW264.7 cells to explore its anti- inflammatory and anti-atherosclerotic mechanisms.

METHODSMurine RAW264.7 cells were pretreated with rosiglitazone at 2.5, 5, and 10 micromol/L prior to exposure to AngII (0.1 micromol/L). TLR4 mRNA level was analyzed by RT-PCR, and TLR4 protein expression by Western blotting. MPO activity in the cell supernatant was assayed by colorimetry. In another experiment, the cells were pretreated with a neutralizing anti-TLR4 antibody (1 mg/L) for 1 h prior to rosiglitazone (10 micromol/L) treatment for 1 h, and subsequently stimulated with AngII or LPS (100 micromol/L) for 24 h to observe the change of MPO activity.

RESULTSRosiglitazone downregulated AngII-induced mRNA and protein expressions of TLR4, and inhibited MPO activity in RAW264.7 cells in a concentration-dependent manner. The TLR4 blocker partially antagonized the effect of AngII on MPO activity, and the inhibitory effect was markedly enhanced by rosiglitazone. Rosiglitazone significantly inhibited LPS (a specific TLR4 ligand)-induced MPO activity in RAW264.7 cells.

CONCLUSIONRosiglitazone downregulates Ang II-induced TLR4 expression in RAW264.7 cells and inhibits MPO secretion possibly by interfering with TLR4 to relieve the inflammatory reaction, which may be one of its anti-atherosclerotic mechanisms.

Angiotensin II ; pharmacology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Cell Line ; Macrophages ; cytology ; metabolism ; Mice ; Peroxidase ; metabolism ; Thiazolidinediones ; pharmacology ; Toll-Like Receptor 4 ; genetics ; metabolism

OBJECTIVETo investigate the anti-hyperglycemic effect and its mechanism of ethanol extraction from Calamintha chinensis (EJCT).

METHODFasting serum glucose (FSG) in normal mice was determined after oral administration of EJCT. Effects of EJCT on hyperglycemia mice induced by adrenaline were investigated by observing the contents of FSG and liver glucogen. Effect of EJCT on the diabetic mice induced by alloxan was investigated by observing the contents of FSG and the injured degree of pancreatic islet. The antilipid-peroxidation of EJCT on liver homogenate was measured by determination of malondiadehyde (MDA) induced by Fe2+/Cys.

RESULTEJCT showed no obvious effect on FSG in normal mice. However, EJCT 300, 600 mg x kg(-1) could remarkably decrease the contents of FSG and increase liver glucogen in hyperglycemia mice induced by adrenaline. In diabetic mice induced by alloxan, EJCT 150, 300, 600 mg x kg(-1) could remarkably decrease the contents of FSG. The damage of pancreatic islet induced by alloxan was also significantly attenuated by EJCT. Furthermore, EJCT 30, 60, 90, 120 mg x L(-1) inhibited lipid peroxidation initiated by Fe2+/Cys in liver homogenate.

CONCLUSIONThese results suggest that EJCT can significantly attenuate hyperglycemia in diabetic mice, which is probably due to decreasing the decomposition of liver glucogen, increasing the synthesis of liver glucogen, antioxidation and amelioration of damaged pancreatic islet.

Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fasting ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Islets of Langerhans ; drug effects ; Lamiaceae ; chemistry ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred ICR

The study was purposed to investigate the effects and mechanism of bone marrow-derived mesenchymal stem cells (MSCs) on graft-versus-host desease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The model of GVHD in rat had been established by allo-HSCT with donor derived T cells. The occurence of GVHD in recipients was observed in condition with or without donor derived MSC co-transplantation. Effects of MSCs on GVHD were analyzed by model rat survival rate and pathology. Proportions of CD4+CD25+ regulatory T cells were determined by using label spleen lymphocytes and thymocytes with double fluorescent-labeled antibodies and flow cytometry. The results showed that MSCs inhibited the lethal GVHD after HSC co-transplantation and increased the survival rate. The ratio of CD4/CD8 deceased in GVHD group in different levels, as compared with that in the experimental group. The proportion of CD4+CD25+ regulatory T cells of spleen lymphocytes was 31.55 +/- 7.58% and 20.90 +/- 1.90% in experimental and GVHD groups, respectively. Similarly, the proportion of CD4+CD25+ regulatory T cells of thymocytes was 93.20 +/- 2.69% and 57.17 +/- 6.79% in experimental and the GVHD groups, respectively. Meanwhile the proportion of CD4+CD25+ regulatory T cells was higher in experimental group than that in GVHD group. It is concluded that MSCs may prevent the lethal GVHD after allo-HSC co-transplantation and raise the survival rate of model rats by acting on the CD4+CD25+ regulatory T cells in vivo.
Animals ; Bone Marrow Cells ; cytology ; Bone Marrow Transplantation ; adverse effects ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Graft vs Host Disease ; immunology ; Interleukin-2 Receptor alpha Subunit ; immunology ; Mesenchymal Stromal Cells ; immunology ; physiology ; Rats ; Rats, Inbred F344 ; Rats, Wistar ; T-Lymphocytes, Regulatory ; immunology

Objective:To explore the development path of improving the intangible assets management, and promoting science and technology transfer of public hospitals.Methods:Analyze and summarize problems and challenges in the identification and disposal of intangible assets related to scientific and technological achievements in the process of technology transfer based on policy research, literature review and practical experience reflection.Results:So far, the identification and measurement norms of intangible assets are not operable enough. Assets evaluation remains controversial and nonstandard.Conclusions:It is recommended to improve the management systems of science and technology transfer and related financial affairs including strengthening the awareness of intangible assets protection, standardizing the management system of intangible assets and optimizing the informatization construction of financial management.

Acupuncture is effective in the treatment of functional dyspepsia, and its mechanism may be related to abnormal gastric motility, central nervous system dysfunction, brain intestinal peptide secretion disorder, plasma molecular metabolite content changes and abnormal gene expression. This article summarized the mechanism of acupuncture treatment for functional dyspepsia in recent years from the aspects of electrophysiology, imaging, molecular biology, metabolism and genomics, and provided basis for clinical treatment of functional dyspepsia.

OBJECTIVETo investigate the dynamic changes of a-AR, b1-AR and b2-AR expression in hepatic fibrosis.

METHODSRat hepatic fibrosis model was established by bile duct ligation (BDL). HE and Masson staining were used to determine hepatic fibrosis levels. Immunohistochemistry was applied to detect alpha -smooth muscle actin (alpha -SMA), a marker of hepatic stellate cell (HSC) activation; Western blot and real-time RT-PCR were used to measure the dynamic changes of alpha -AR, beta(1)-AR, beta(2)-AR expression on protein and mRNA levels, respectively, during the development of hepatic fibrosis.

RESULTS(1) HE and Masson trichrome staining showed that the liver fibrosis models were established successfully. (2) At 1, 2, 3, 4 wk after BDL, alpha -SMA positive area density of the model group (10.58% +/- 1.75%, 24.14% +/- 2.02%, 29.74% +/- 2.59%, 34.28% +/- 2.01%) was significantly higher than that of the sham operation group (4.12% +/- 1.51%), P less than 0.01. (3) The expression of alpha -AR, beta(1)-AR, beta(2)-AR protein and mRNA was increased with the development of the hepatic fibrosis (P less than 0.05). (4) alpha -SMA expression was positively associated with alpha -AR, beta(1)-AR, beta(2)-AR, r values were 0.564, 0.753 and 0.606, respectively.

CONCLUSIONThe expression of alpha -SMA is increased dramatically during the fibrosis, and is positively associated with the expression of alpha -AR, beta(1)-AR and beta(2)-AR.

Actins ; metabolism ; Animals ; Hepatic Stellate Cells ; metabolism ; pathology ; Immunohistochemistry ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Biliary ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Male ; Polymerase Chain Reaction ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha ; genetics ; metabolism ; Receptors, Adrenergic, beta ; genetics ; metabolism ; Sympathetic Nervous System ; metabolism ; Time Factors

Objective To analyze the correlation between the pressure volume parameters and cardiac function in terms of New York Heart Association(NYHA) classification in patients with pulmonary arterial hypertension. Methods Among 36 patients with pulmonary hypertension admitted in our center between April 2015 to June 2016, right heart catheterization recording right atrial pressure curve,right ventricular pressure curve,pulmonary arterial pressure and oxygen saturation curve in different parts was performal.All patients recived underwent cardiac MRI examination to obtain a single cardiac cycle and the use of Mass software to measure right ventricular volume continuously and right ventricular pressure-volume loop parameters were then obtained. Patients were divided into different groups according to the NYHA functional classification, and the correlation between the parameters of each group and the cardiac function classes a were analyzed. Results Compare to patients with NYHA class Ⅰheart function,patients with NYHA heart function class Ⅱ and class Ⅲ had significantly higher right ventricular end diastolic pressure(P < 0.05)and higher right ventricular systolic pressure (P < 0.01). Spearman correlation analysis showed that cardiac function of NYHA classⅠ,Ⅱ and Ⅲhad position correlation with RVESV,RVEDP and RVESP wheras negative correlation with RVEDV. ROC curve analysis showed that,when the patients were divided into 2 groups as NYHAⅠvs. NYHA class Ⅱ + Ⅲ,NYHA classification for predicting the outcome of the NYHA class Ⅱ + Ⅲ level, pulmonary artery elasticity and right ventricular end systolic pressure had larger area under curves respectively. Conclusions Pressure-volume parameters of right ventricles are more objective indicators for cardiac function assessment for pulmonary hypertension patients and evaluation of disease progression especialy in patients with mild symptoms.

OBJECTIVETo study the effects of different dietary fatty acid on the expression of nuclear receptor genes in the breast cancer of rats.

METHODSFifty-day-old female Sprague-Dawley rats were fed on eight different diets containing following fatty acids: saturated fatty acid (SFA); monounsaturated fatty acid (MUFA); n-6 polyunsaturated fatty acid (PUFA); n-3 PUFA; 1:1 n-6/n-3; 5:1 n-6/n-3; 10:1 n-6/n-3; 1:2:1 S/M/P (n-6/n-3 at 1:1). The rats were given a single intraperitoneal injection of methyl-nitrosourea (MNU) at 50 mg/kg body weight to establish the rat model of mammary carcinogenesis, the ultrastructure changes of mammary gland cells in rats were observed by transmission electron microscope, the cell proliferation activity was detected by BrdU-labeled immunocytochemistry, and the expression of PPARbeta and PPARgamma mRNA were assayed by RT-PCR.

RESULTSThere was no breast cancer occurring in control groups and the MNU-treated n-3 PUFA group, and the ultrastructure and proliferation activity of mammary gland cells in these groups were normal. In contrast, there appeared obvious marker of adenocarcinomas in mammary gland cells of MNU-induced breast cancer, and a high cell proliferation activity was found in tumor growth-enhancing groups (SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3 and S/M/P, 21% - 22% of BrdU-labeled cells), while a low cell proliferation activity was detected in rats fed with 1:1 n-6/n-3 diet (13% of BrdU-labeled cells, P < 0.05). Moreover, peroxisome proliferator-activated receptors (PPARs), as important nuclear receptor genes of relating lipid metabolism, the expressions of PPARbeta and PPARgamma mRNA were significantly up-regulated in mammary adipose tissues of MNU-induced breast cancer as compared with the control groups, but the expression levels of peroxisome proliferator-activated receptors (PPARs) in rats fed with 1:1 n-6/n-3 group were lowest (P < 0.05).

CONCLUSIONThe different dietary fatty acid compositions should diversely adjust the expression of PPARs gene in rats, which maybe have an important role in affecting incidence of breast cancer.

Animals ; Fatty Acids ; pharmacology ; Fatty Acids, Omega-3 ; pharmacology ; Fatty Acids, Omega-6 ; pharmacology ; Fatty Acids, Unsaturated ; pharmacology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Mammary Neoplasms, Experimental ; genetics ; PPAR gamma ; genetics ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo detail our early experience and technique of a modified two-stage reimplantation protocol using antibiotic-loaded articulating cement spacers (ALACSs) for treatment of late periprosthetic infection after total knee arthroplasty (TKA).

METHODSFrom January 2006 to February 2009, a series of 21 patients (21 knees) with late infected TKAs were treated by radical debridement and removal of all components and cement, and then articulating spacers were implanted using antibiotic-impregnated bone cement. For this purpose, 4 g vancomycin powder was mixed with per 40 g cement. Graduated knee motion and partial weight bearing activity were encouraged in the interval period. Each patient received an individual systemic organism-sensitive antimicrobial therapy for 4.9 (range, 2-8) weeks followed by a second-stage TKA revision. All the patients were regularly followed up using the American Knee Society Scoring System.

RESULTSEach case underwent a successful two-stage exchange and had infection eradicated, none had recurrent infection after an average of 32.2 (range, 17-54) months of follow-up. Preoperatively, the mean knee score was 53.5 points, function score was 27.3 points, pain score was 25.7 points, range of motion (ROM) was 82.0 degree extensor lag was 2 degree Between stages, the mean knee score was increased to 61.3 points, function score to 45 points, pain score to 35 points, ROM to 88.2 degree and extensor lag to 3.4 degree At final follow-up, the mean knee score was further increased to 82.1 points, function score to 74.5 points, pain score to 42.1 points, ROM to 94.3 degree and knee extension lag to 1.9 degree The interval period was 11.5 (range, 6-32) weeks. The amount of bone loss was unchanged between stages. No patient developed noticeable dysfunction of the liver or kidney or other complications such as impaired wound healing, deep venous thrombosis, pulmonary embolism, cerebrovascular accidents, etc.

CONCLUSIONSTreating infected TKA with ALACS avoids spacer-related bone loss, preserves knee function between stages, and eradicates infection effectively without significant complications. The early clinical results are inspiring. The authors believe that radical and repeated (if needed) debridement, individual application of systemic antibiotics, and reasonable timing judgement upon the secondary revision are all key factors related to a successful outcome with two-stage reimplantation procedure for infected TKA.

Anti-Bacterial Agents ; Arthroplasty, Replacement, Knee ; Humans ; Knee Joint ; Knee Prosthesis ; Prosthesis-Related Infections