Levels Of Platelet-derived Growth factor-BB Research Articles

Root of Polygonum cuspidatum extract reduces progression of diabetes-induced mesangial cell dysfunction via inhibition of platelet-derived growth factor-BB (PDGF-BB) and interaction with its receptor in streptozotocin-induced diabetic rats.

BackgroundPlatelet-derived growth factor–BB (PDGF-BB) is highly expressed in the renal tissues of patients with diabetic nephropathy, and it plays an important role in the initiation and progression of diabetic nephropathy. The aim of this study was to evaluate the protective effects of root of Polygonum cuspidatum extract (PCE) on early renal glomerular proliferation in streptozotocin (STZ)-induced diabetic rats.MethodsPCE (100, 350 mg/kg/day) was administered to diabetic rats for 16 weeks. Blood glucose and albuminuria were measured. Renal histology, α-smooth muscle actin (α-SMA), and proliferating cell nuclear antigen (PCNA) expression levels were also examined.ResultsAfter 16 weeks of treatment with PCE, severe hyperglycemia and albuminuria were observed in the diabetic rats. The expressions levels of α-SMA and PCNA proteins were significantly increased in the glomeruli of the diabetic rats. The expression levels of PDGF-BB and its receptor expressions were greatly increased in the glomeruli of the diabetic rats. However, PCE markedly reduced albuminuria in the diabetic rats. PCE inhibited α-SMA and PCNA up-regulation and ameliorated PDGF-BB and PEGFR-ß protein expression in the diabetic rats. In addition, the binding of PDGF-BB/PDGFR-ß was inhibited by PCE as shown by an in vitro assay.ConclusionsThese results suggest that PCE has an inhibitory effect on mesangial proliferation in diabetic renal tissues via the inhibition of the interaction of PDGF-BB with its receptor. PCE may have beneficial effects in preventing the progression of diabetic nephropathy.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-477) contains supplementary material, which is available to authorized users.

Blood neutrophil to lymphocyte ratio as a predictor in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy.

Inflammation plays a critical role in cancer. The aim of the present study was to investigate the impact of neutrophil to lymphocyte ratio (NLR) on patients with advanced hepatocellular carcinoma (HCC) treated with hepatic arterial infusion chemotherapy (HAIC). We retrospectively evaluated 266 patients with advanced HCC treated with HAIC between March 2003 and December 2012. NLR was calculated from the differential leukocyte count by dividing the absolute neutrophil count by the absolute lymphocyte count. The cut-off level of NLR was set as the median value of 2.87 among all patients in this study. The objective response rate in the patients with low NLR was 37.6%, which was significantly better than that of the patients with high NLR (21.1%; P < 0.01). Multivariate analysis revealed that low NLR remained associated with the response to HAIC (P = 0.024). Median progression-free survival and median overall survival in patients with high NLR were 3.2 and 8.0 months, respectively, which were significantly shorter than that of the patients with low NLR (5.6 and 20.7 months; P < 0.01 and P < 0.01, respectively). High NLR was an independent unfavorable prognostic factor in multivariate analysis. The patient outcome was stratified more clearly by NLR calculated after HAIC added to calculations before HAIC. Serum platelet-derived growth factor-BB level was positively correlated with NLR. Results suggest that NLR is a useful predictor in patients with advanced HCC treated with HAIC. These findings may be useful in determining treatment strategies or in designing clinical chemotherapy trials in future.

PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis.

Osteogenesis during bone modeling and remodeling is coupled with angiogenesis. A recent study shows that the specific vessel subtype, strongly positive for CD31 and Endomucin (CD31hiEmcnhi), couples angiogenesis and osteogenesis. We found that preosteoclasts secrete platelet derived growth factor-BB (PDGF-BB), inducing CD31hiEmcnhi vessels during bone modeling and remodeling. Mice with depletion of PDGF-BB in tartrate-resistant acid phosphatase positive (TRAP+) cell lineage (Pdgfb–/–) show significantly lower trabecular and cortical bone mass, serum and bone marrow PDGF-BB concentrations, and CD31hiEmcnhi vessels compared to wild-type mice. In the ovariectomized (OVX) osteoporotic mouse model, concentrations of serum and bone marrow PDGF-BB and CD31hiEmcnhi vessels are significantly decreased. Inhibition of cathepsin K (CTSK) increases preosteoclast numbers, resulting in higher levels of PDGF-BB to stimulate CD31hiEmcnhi vessels and bone formation in OVX mice. Thus, pharmacotherapies that increase PDGF-BB secretion from preosteoclasts offer a novel therapeutic target for osteoporosis to promote angiogenesis for bone formation.

Circulating keratan sulfate as a marker of metabolic changes of cartilage proteoglycan in juvenile idiopathic arthritis; influence of growth factors as well as proteolytic and prooxidative agents on aggrecan alterations.

The aim of this study was to evaluate the plasma keratan sulfate (KS) level as a potential marker of joint damage in children with juvenile idiopathic arthritis (JIA). The influence of growth factors as well as proteolytic and prooxidative agents on aggrecan alterations were evaluated in this study. Plasma levels of KS, transforming growth factor β1 (TGF-β1), platelet-derived growth factor BB (PDGF-BB), a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS-4 and ADAMTS-5), and thiol groups (TG) were quantified in samples obtained from 30 healthy subjects and 30 patients with JIA before and after treatment. Increased (p<0.01) plasma KS was observed in JIA patients before treatment. Therapy resulted in a decrease in KS level. However, plasma KS level remained higher (p<0.05) than in controls. Increased levels of TGF-β1 (p<0.01) and PDGF-BB (p<0.05) in untreated JIA patients were recorded. Clinical improvement was accompanied by significant decrease in TGF-β1 and PDGF-BB, compared with a pretreatment condition and a control group. The concentrations of proteinases were characterized by different trends of alterations. When the ADAMTS-4 level increased (p<0.01) in the blood of untreated patients, the concentration of ADAMTS-5 was found to be reduced (p<0.0001), compared with controls. JIA treatment resulted in the normalization of ADAMTS-4 level. Plasma TG concentration was decreased only in untreated patients (p<0.05). We have revealed a significant correlation between plasma KS level and ADAMTS-4, TGF-β1, TG, C-reactive protein, and erythrocyte sedimentation rate levels. Plasma KS level in JIA patients, reflecting the aggrecan structure, indicates that treatment that modifies inflammation simultaneously does not contribute to total regeneration of articular matrix components and signalizes the need for further treatment.

AB0157 Effects of Anti-TNF Therapy on Markers of Angiogenesis and Vascular Disease in Rheumatoid Arthritis: A Comparative Approach

BackgroundAccelerated atherosclerosis, increased cardiovascular (CV) morbidity and mortality, as well as the perpetuation of angiogenesis and abundant production of angiogenic factors have been associated with rheumatoid arthritis (RA) and ankylosing...

Investigating the Association between Angiogenic Cytokines and Corneal Neovascularization in Sulfur Mustard Intoxicated Subjects 26 Years after Exposure.

Objectives:This study aimed to evaluate the associations between the concentrations of three major angiogenic cytokines–vascular endothelial growth factor-A165 (VEGF-A165), basic fibroblast growth factor (bFGF), and platelet-derived growth factor-BB (PDGF-BB)–in the tear of sulfur mustard (SM)-exposed subjects and corneal neovascularization (CNV) 26 years after exposure.Materials and Methods:The concentrations of VEGF-A, bFGF, and PDGF-BB were measured by enzyme-linked immunosorbent assay (ELISA) in reflex tears of (i) SM-injured patients with CNV (positive case group including 18 individuals) and (ii) SM-injured patients without CNV (negative case group including 22 individuals). Then results were compared to corresponding values obtained from tears of 40 healthy control subjects.Results:The mean concentrations of all investigated growth factors, VEGF-A165, bFGF, and PDGF-BB, were significantly higher in positive cases than controls (P ≤ 0.001, P = 0.028, and P = 0.041, respectively). Whereas, VEGF-A165 was the only growth factor which displayed significantly elevated concentrations in negative case group compared to the healthy individuals (P = 0.030). Additionally, the mean level of VEGF-A165 was also higher in positive patient group than negative patients (P = 0.022). Subjects with increased concentrations of tear VEGF-A165 were more than 10 times more likely to suffer from CNV than normal individuals (odds ratio (OR) = 10.43, confidence interval (CI): 2.14–38.46, P = 0.001), while elevated levels of bFGF and PDGF-BB increased the risk of CNV by about twofold.Conclusion:Although all investigated cytokines had increased in tears of positive patients, VEGF-A was the only one which showed a significant correlation with the severity of CNV, and thus played a crucial role in corneal angiogenesis.

Expression of angiogenesis regulatory proteins and epithelial-mesenchymal transition factors in platelets of the breast cancer patients.

Platelets play a role in tumor angiogenesis and growth and are the main transporters of several angiogenesis regulators. Here, we aimed to determine the levels of angiogenesis regulators and epithelial-mesenchymal transition factors sequestered by circulating platelets in breast cancer patients and age-matched healthy controls. Platelet pellets (PP) and platelet-poor plasma (PPP) were collected by routine protocols. Vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), thrombospondin-1 (TSP-1), platelet factor 4 (PF4), and transforming growth factor-β1 (TGF-β1) were measured by enzyme-linked immunosorbent assay. Angiogenesis-associated expression of VEGF (2.1 pg/106 platelets versus 0.9 pg/106 platelets, P < 0.001), PF4 (21.2 ng/106 platelets versus 10.2 ng/106 platelets, P < 0.001), PDGF-BB (42.9 pg/106 platelets versus 19.1 pg/106 platelets, P < 0.001), and TGF-β1 (15.3 ng/106 platelets versus 4.3 ng/106 platelets, P < 0.001) differed in the PP samples of cancer and control subjects. In addition, protein concentrations were associated with clinical characteristics (P < 0.05). Circulating platelets in breast cancer sequester higher levels of PF4, VEGF, PDGF-BB, and TGF-β1, suggesting a possible target for early diagnosis. VEGF, PDGF, and TGF-β1 concentrations in platelets may be associated with prognosis.

Protective effects of L-carnitine, N-acetylcysteine and genistein in an experimental model of liver fibrosis

Liver fibrosis is a reversible wound-healing response that occurs following liver injury. In this study, we aimed to investigate the possible protective effects of L-carnitine, N-acetylcysteine and genistein in liver fibrosis induced by carbon tetrachloride (CCl4). In addition, the effects of these agents were compared in the same study. In this study, rats were randomly allocated into 8 groups, consisting of 10 rats each, as follows: a control group, CCl4, L-carnitine, N-acetylcysteine, genistein, CCl4 and L-carnitine, CCl4 and N-acetylcysteine, and CCl4 and genistein. At the end of 6 weeks, blood and liver tissue specimens were collected. Alanine aminotransferase (ALT); aspartate aminotransferase (AST); complete blood count, tumor necrosis factor-α (TNF-α); platelet-derived growth factor-BB (PDGF-BB); interleukin-6 (IL-6); liver glutathione level; oxidant/antioxidant status; scores of hepatic steatosis, necrosis, inflammation, and fibrosis; and the expression of α-smooth muscle actin were studied. Although the ALT and AST values in the group administered CCl4 were significantly higher than in all the other groups (P<0.05), there was no significant difference between the control group and the groups administered CCl4 combined with L-carnitine, N-acetylcysteine and genistein (P>0.05). There were significant differences in the levels of TNF-α, PDGF-BB and IL-6 (P<0.05) between the CCl4 group and the groups with L-carnitine, N-acetylcysteine and genistein added to CCl4. N-acetylcysteine and genistein had positive effects on the oxidant/antioxidant status and on liver necrosis and fibrosis scores. In our study, L-carnitine, N-acetylcysteine and genistein showed significant protective effects in liver fibrosis induced by CCl4.

Significance of Serum TGF-β1 Levels for Estimating Bilirubin Decrease Following Biliary Drainage in Jaundiced Patients Caused by Biliary Tract Carcinoma

Purpose: Biliary drainage is generally performed in patients with obstructive jaundice (OJ) before major hepatectomy for biliary tract carcinomas. However, estimation of bilirubin decrease rate after biliary drainage may be often difficult. In this study, we investigated useful biochemical marker for estimating a period for bilirubin decrease, and also studied mechanisms responsible for delayed bilirubin reduction. Methods: Peripheral blood samples were taken in 22 patients with OJ caused by biliary tract carcinoma before and after biliary drainage. Serum transforming growth factor-β1 (TGF- β1) and platelet-derived growth factor BB (PDGF-BB), and bilirubin decrease rates (“b”value) were investigated. Expression of desmin and α-smooth muscle actin (α-SMA) in surgically resected liver specimens were also investigated in 12 patients who underwent radical surgery, using immunohistochemical staining, to evaluate hepatic stellate cell (HSC) status. Results: Serum TGF- β1 and PDGF-BB levels were significantly higher in patients with OJ than in controls (p<0.01). Serum levels of total bilirubin and TGF- β1 decreased significantly following biliary drainage. However, bilirubin reduction in patients with high TGF- β1 was significantly slower than those with low TGF- β1, despite of the height of the serum bilirubin levels before drainage. Immunohistochemical studies revealed increased number of HSCs (desmin-positive cells) and activated HSCs (α-SMA-positive cells) in portal areas of the liver in patients with the high TGF- β1 at surgery. Conclusion: Serum TGF- β1 mostly produced by activated HSCs, reflecting hepatic damage by cholestasis, may be a useful biochemical marker for predicting the period of bilirubin reduction in patients with OJ.

Preventative effect of Astragalus flavescens on hepatic fibrosis in rats and its mechanism of action

The aim of this study was to investigate the preventative effect of Astragalus flavescens on hepatic fibrosis in rats and its mechanism of action. A total of 60 rats were randomly divided into normal control, model control, high-dose treatment and low-dose treatment groups, and a hepatic fibrosis model was established. The high- and low-dose treatment groups were treated with 2 g/100 g and 0.5 g/100 g Astragalus flavescens, respectively, once a day. Eight weeks following the initiation of treatment, the liver specimens of the rats were stained and observed under a light microscope. Hepatic fibrosis indices, specifically, type III precollagen (PC III), type IV collagen (C IV), hyaluronic acid (HA) and laminin (LN), were detected. Furthermore, the expression and localization of the hepatic fibrosis-related factors transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and platelet-derived growth factor-BB (PDGF-BB) were determined. The serum levels of hepatic fibrosis indices, and the liver tissue levels of hepatic fibrosis-related factors and collagen surface density in the model control group and the high- and low-dose treatment groups were significantly higher compared with those of the normal control group (P<0.05). In addition, the values in the two treatment groups were significantly lower compared with those of the model control group (P<0.05). The present study demonstrated that Astragalus flavescens effectively prevents hepatic fibrosis in rats. A possible mechanism for this is that it may reduce the expression levels of TGF-β1, PDGF-BB and CTGF, thereby inhibiting the activation of hepatic stellate cells and specifically blocking the signal transduction pathway of hepatic fibrosis.

Clinical effect of low-dose cyclophosphamide and prednisone in treatment of multiple myeloma and its influence on serum VEGF, PDGF-BB levels

Objective To investigate the clinical effect of low-dose cyclophosphamide plus prednisone(CP regimen) in treatment of multiple myeloma(MM) and its influence on serum levels of vascular endothelial growth factor(VEGF) and platelet-derived growth factor BB(PDGF-BB).Methods Totally 54 patients with refractory or relapse MM were continuously treated with CP regimen: oral cyclophosphamide(CTX,50 mg/d) and prednisone(Pred,15 mg/d).The peripheral blood samples were collected from each group 0,2,4,and 6 months after treatment.Serum VEGF and PDGF-BB levels were analyzed by ELISA.Results The overall effective rate was up to 69%(36/52) in our study.The treatment was effective in 30 patients,including 2 complete response(CR) cases,4 very good partial response(VGPR) cases and 24 partial response(PR) cases,and their serum samples were examined for 4 times.The serum levels of VEGF and PDGF-BB were significantly decreased in the 30 patients at 2,4,and 6 months after treatment(P0.01);while their levels were not significantly change in the 7 invalid patients 2 months after treatment compared with before treatment.Conclusion Low-dose cyclophosphamide plus prednisone has noticeable effect in treatment of MM patients;it can also greatly down-regulate serum VEGF and PDGF-BB levels.The mechanisms of CP regimen in MM patients may be associated with the inhibition of new blood vessel generation.

865P - A Cytokine and Angiogenic Factor (CAF) Analysis in Plasma in Testicular Germ Cell Tumor Patients

ABSTRACT Background Testicular germ-cell tumours (TGCTs) represent a model for the cure of cancer. Nonetheless, a small proportion of patients develop disease recurrence. We investigated cytokines and angiogenic factors (CAFs) in patients with TGCTs. We aimed to link the CAF profile to PFS and select candidate predictive and prognostic markers for further study. Methods In this ongoing translational study, plasma from 55 patients with TGCTs was collected. The concentrations of 51 plasma CAFs were measured pretreatment (n = 47) and on day 22 (n = 30) using multiplex bead arrays (Human Group I and II cytokine panels and TGF beta by Bio-Plex 200 system (Bio-Rad Laboratories, Hercules, CA). We investigated the association between baseline levels of CAFs and clinico-pathological variables. Results We observed elevated level of transforming growths factor beta1 (TGF-b1), IL-2Ra, CXCL9, CXCL10, IFN-gama, macrophage inflammatory protein-1b (MIP-1b), and platelet-derived growth factor-BB (PDGF-BB) in seminoma patients compared to non-seminoma. Patients with poor prognosis according to IGCCCG have elevated pretreatment level of beta-nerve growth factor (NGF-b) and stromal cell-derived factor-1 (SDF-1a) compared to patients with good/intermediate prognosis. Patients with metastatic disease had elevated pretreatment level of stem cell growth factor beta (SCGF-b) and PDGF-BB compared to patients with stage I disease. Conclusions Using CAF profiling, we revealed differences in subgroups of TGCTs patients. We suggest that this platform may provide valuable insights into TGCTs biology, and could be useful in identification of new therapeutic targets. Disclosure All authors have declared no conflicts of interest.

Comparison of Tear Cytokines and Clinical Outcomes Between Off-flap and On-flap Epi-LASIK With Mitomycin C

To compare tear cytokines and clinical outcomes between off-flap and on-flap epi-LASIK eyes and explore the possible mechanism for the clinical differences. This double-masked, randomized study enrolled 18 myopic patients who underwent off-flap epi-LASIK with mitomycin C (MMC) in 1 eye and on-flap epi-LASIK with MMC in the contralateral eye. Tears were collected from each eye preoperatively and 2 hours, 1 day, and 5 days postoperatively. Concentrations of multiple tear cytokines were measured by a multiplex immunobead assay. Uncorrected distance visual acuity (UDVA), refraction, haze scores, pain scores, and percentage of corneal epithelial healing were evaluated. Compared with the on-flap group, the off-flap group had outcomes of better UDVA and higher percentages of epithelial healing at 5 days after surgery (P<.001) and lower levels of haze at 1 month after surgery (P=.049). Preoperatively, no significant differences were noted in the release rate of all tear cytokines between groups. At 2 hours postoperatively, the release rate of tear basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF-BB), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in the off-flap group were significantly lower than those in the on-flap group (P=.011, .017, .048, and .041, respectively). Off-flap epi-LASIK with MMC offers faster corneal epithelial healing and visual recovery, and temporary less haze than on-flap epi-LASIK with MMC. The lower tear levels of bFGF, PDGF-BB, IL-8, and TNF-α in the offflap group 2 hours after surgery may suggest a possible mechanism for the clinical differences.

Serum platelet-derived growth factor-BB in adult patients with aggressive non-Hodgkin's lymphoma

Background The importance of angiogenesis was proved first for solid tumors, and its importance in hematological malignancies was reported later. Aim of the work The present study aimed to evaluate the prognostic value of the angiogenesis marker platelet-derived growth factor-BB (PDGF-BB) in patients with aggressive non-Hodgkin’s lymphoma (NHL) and identify its significance on treatment response. Subjects and methods The serum level of PDGF-BB was measured in patients with aggressive NHL before and after chemotherapy and compared with that of a healthy control group, and its relationship with certain prognostic parameters was assessed. Results Pretreatment serum level of PDGF-BB did not show a significant change as compared with the control group. Its level showed no relation to Ann Arbor stages, International Prognostic Index scores, B symptoms, or extranodal involvement. Chemotherapy led to a considerable increase in serum PDGF-BB level in all NHL patients and in the noncomplete responder subgroup. Conclusion From the results mentioned above it could be concluded that PDGF-BB is not vital in the pathogenesis of NHL. Chemotherapy led to elevation of serum PDGF-BB, reflecting activation of angiogenesis, which can be considered one of the mechanisms of conferring chemoresistance to cancer cells or in identification of patients at risk for developing side effects. Future studies are recommended to prove this effect of chemotherapy. If this effect is confirmed, the use of agents blocking the angiogenic pathway of PDGF-BB in combination with chemotherapy may improve the therapeutic effectiveness and sensitize chemoresistant cells.

Coordinated Increase in Serum Platelet-Derived Growth Factor-BB and Transforming Growth Factor-β1 in Patients with Chronic Pancreatitis

Background: In vitro studies suggest that platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-β1 (TGF-β1) play an important role in pancreatic fibrosis. The aim of this study was to evaluate serum PDGF-BB and TGF-β1 concentrations in patients with chronic pancreatitis (CP). Methods: Forty male patients with a history of alcoholic CP and 35 age-matched healthy subjects were examined. Serum concentrations of PDGF-BB, TGF-β1, laminin and hyaluronic acid were determined by ELISA assay. Additionally, we determined serum concentrations of PDGF-BB and TGF(31 in patients with functional dyspepsia, ulcerative colitis and Crohn's disease. Results: Patients with advanced CP had significantly higher serum PDGF-BB and TGF-β1 concentrations compared to control subjects. A strong positive correlation between serum PDGF-BB and TGF-β1 concentrations was found in patientswith CP. Serum laminin and hyaluronic acid were also elevated in patients with CP. No increase in serum PDGF-BB and TGF-β1 concentrations was found in patients with functional dyspepsia, ulcerative colitis or Crohn's disease. Conclusion: The obtained results indicate for the first time that serum levels of PDGF-BB are elevated in patients with CP. However, ROC curve analysis suggests that PDGF-BB is not superior to laminin as a potential marker of advanced CP.

Platelet‐Derived Growth Factor‐BB Release Profile in Gingival Crevicular Fluid After Use of Marginal Periosteal Pedicle Graft as an Autogenous Guided Tissue Membrane to Treat Localized Intrabony Defects

The aim of this study is to evaluate levels of platelet-derived growth factor-BB (PDGF-BB) in gingival crevicular fluid (GCF) during the early stages of healing for sites treated by marginal periosteal pedicle (MPP) graft as an autogenous guided tissue membrane compared to that of the control open flap debridement (OFD). Fifteen non-smoking patients (13 males and 2 females) with severe chronic periodontitis participated in this prospective, controlled, masked trial. Each subject contributed matched pairs of 2- or 3-walled intrabony interproximal defects in premolar or molar teeth. Interproximal contralateral defects were randomly assigned to either the MPP group 1 or control OFD group 2. GCF samples were collected at 1, 3, 7, 14, and 30 days after surgery. PDGF-BB in the GCF samples was measured using a human PDGF-BB enzyme-linked immunosorbent assay kit. In both MPP and OFD, PDGF-BB concentrations peaked in the samples obtained during the early postoperative days (days 2 and 3) and decreased sharply in the samples obtained 7, 14, and 30 days post-surgery. Periosteal coverage of periodontal defects is not associated with a significant increase in PDGF-BB levels.

Idiopathic and secondary osteonecrosis of the femoral head show different thrombophilic changes and normal or higher levels of platelet growth factors

Background and purpose Thrombophilia represents a risk factor both for idiopathic and secondary osteonecrosis (ON). We evaluated whether clotting changes in idiopathic ON were different from corticosteroid-associated ON. As platelet-rich plasma has been proposed as an adjuvant in surgery, we also assessed whether platelet and serum growth factors were similar to those in healthy subjects.Methods 18 patients with idiopathic ON and 18 with corticosteroid-associated ON were compared with 44 controls for acquired and inherited thrombophilia. Platelet factor 4 (PF4), transforming growth factor-β1, platelet-derived growth factor-BB (PDGF-BB), and vascular endothelial growth factor were assayed in the supernatants of thrombin-activated platelets, in platelet lysates, and in serum from 14 ON patients and 10 controls.Results Idiopathic ON patients had higher plasminogen levels (median 118%) than controls (101%) (p = 0.02). Those with corticosteroid-associated ON had significantly higher D-dimer (333 ng/mL) and lower protein C levels (129%) than controls (164 ng/mL, p = 0.004; 160%, p = 0.02). The frequency of inherited thrombophilia was not different from the controls. No statistically significant differences were found between idiopathic and corticosteroid-associated ON. 20 of the 36 ON patients were smokers. (The controls were selected from smokers because nicotine favors hypercoagulability). ON patients had significantly higher serum PF4 levels (7,383 IU/mL) and PDGF-BB levels (3.1 ng/mL) than controls (4,697 IU/mL, p = 0.005; 2.2 ng/mL, p = 0.02).Interpretation Acquired hypercoagulability was common in both ON types, but the specific changes varied. The release of GF from platelets was not affected, providing a biological basis for platelet-rich plasma being used as an adjuvant in surgical treatment.

Soy isoflavone delays the progression of thioacetamide-induced liver fibrosis in rats

Objective. Our aim was to investigate the effect of soy isoflavone (SI) on liver fibrosis in a thioacetamide (TAA)-induced rat model. Materials and methods. Twenty-eight rats were assigned to four groups: sham group, fibrosis group, low-dose treatment group (LDg) and high-dose treatment group (HDg). SI (90 or 270 mg/kg) was administered daily during the model development by TAA. Standard liver tests, platelet derived growth factor-BB (PDGF-BB) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured. The expression of collagen, α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) in liver tissue was determined. Electron microscopy was used to perform ultrastructural analysis of the livers. Results. Hepatic fibrosis was induced by 8 weeks of TAA administration. However, following the administration of SI, collagen staining significantly declined as compared with the fibrosis group (p < 0.01). Less collagen fibers around the hepatic stellate cells (HSCs) were observed in HDg as compared to the fibrosis group and LDg. There was no significant difference in standard liver tests between the fibrosis group and the two treatment groups. The levels of PDGF-BB and TIMP-1 in the two SI-treated groups were significantly lower than in the fibrosis group (p < 0.01). The expression of α-SMA and TGF-β1 in HDg was less than that in the fibrosis group and LDg (p < 0.01). Conclusion. Administration of a high dose of SI resulted in an obvious inhibitory effect on liver fibrosis induced by TAA in rats. One hypothesis is that the effect may be related to the inhibition of HSC activation and proliferation.

Platelet-Derived Growth Factor BB Mediates the Tropism of Human Mesenchymal Stem Cells for Malignant Gliomas

Bone marrow-derived human mesenchymal stem cells (hMSCs) are capable of localizing to gliomas after systemic delivery and can be used in glioma therapy. However, the mechanism underlying the tropism of hMSCs for gliomas remains unclear. In vitro studies suggest that platelet-derived growth factor BB (PDGF-BB) may mediate this tropism. However, a causal role of PDGF-BB has not been demonstrated in vivo. Therefore, we tested the hypothesis that PDGF-BB mediates the attraction of hMSCs to gliomas in vitro and in vivo. U87 or LN229 glioma cells were transfected with plasmids encoding human PDGF-B. Stable transfected clones that secreted large amounts of PDFG-BB and clones that produced low levels of PDGF were chosen. In vitro migration of hMSCs toward PDGF-B or conditioned media from high- and low-secreting PDGF-B tumor cells was assessed using Matrigel invasion assays. For in vivo localization studies, hMSCs were tracked by bioluminescence imaging (BLI) after transduction with an adenovirus containing luciferase cDNA. In other studies, hMSCs were labeled with green fluorescent protein (gfp) and analyzed for intratumoral localization by immunohistochemistry. In vitro invasion assays showed that significantly more hMSCs migrated toward glioma cells engineered to secrete high levels of PDGF-BB compared with low-secreting gliomas. Anti-PDGF-BB-neutralizing antibody abrogated this increase in migration. Pretreatment of hMSCs with inhibitory antibodies against PDGF receptor-beta also reduced hMSC migration. To demonstrate that PDGF-BB mediates the localization of hMSCs in vivo, hMSCs-Ad-Luc were injected into the carotid artery of mice harboring orthotopic 7-day-old U87-PDGF-BB-high secreting or U87-PDGF-BB-low secreting xenografts and analyzed by BLI. Statistically significant increases in hMSCs were seen within PDGF-BB-high xenografts compared with PDGF-BB-low xenografts. To control for PDGF-BB-induced differences in tumor size and vascularity, gfp-labeled hMSCs were injected into the carotid arteries of animals harboring 4-day old PDGF-BB-high secreting xenografts or 7-day old PDGF-BB-low secreting xenografts. At these times tumors had similar size and vessel density. Statistically significant more hMSCs localized to PDGF-BB-high secreting xenografts compared with PDGF-BB-low secreting xenografts. Pretreatment of hMSCs with anti-PDGFR-beta-inhibitory antibodies decreased the localization of hMSCs in this intracranial model. PDGF-BB increases the attraction of hMSCs for gliomas in vitro and in vivo, and this tropism is mediated via PDGF-beta receptors on hMSCs. These findings can be exploited for advancing hMSC treatment.

Occupational exposure to bacterial single cell protein induces inflammation in lung and blood

Bacterial single cell protein (BSCP) is used as a protein enrichment in livestock and fish feed, and is extracted from dried bacterial mass. In the production of BSCP, workers are exposed to organic dust containing high levels of endotoxins that may induce acute airway inflammation. However, the long term effect on the airways of such exposure is not known, and we have examined inflammatory markers in induced sputum and blood among BSCP exposed workers. We included 21 non-smoking production workers (age 31–42 (range; mean 35)) without respiratory symptoms and 21 healthy non-exposed references (age 21–52 (range; mean 34)). Airborne endotoxin concentrations were measured, and induced sputum samples and blood samples were collected from the workers and non-exposed references. The airborne endotoxin concentration measured in inhaled air during the work shift was 430 EU/m3 (50–2000) (median (range)). The percentage of neutrophils in induced sputum was 79% (66–93) (median (25th–75th percentiles)) and 31% (25–45) (p < 0.001) for operators and references, respectively. Protein analysis in induced sputum supernatant showed significantly elevated levels of interleukins IL-1β and IL-12 (p < 0.05), while blood analysis showed significantly elevated levels of PDGF-BB (platelet-derived growth factor-BB) and RANTES (regulated upon activation normally T cell expressed and secreted) (p < 0.05). Workers exposed to BSCP had an airway inflammation characterized by a high level of neutrophils. However, only a few cytokines were elevated in lung and blood, which could imply low inflammatory activity suggestive of possible adaptation mechanisms due to daily exposure to BSCP, or that the inflammation reaction was a dose-related response occurring at higher levels.