Role of TGF-ß1 and PDGF-B in Crimean-Congo hemorrhagic fever in Eastern Anatolia Region in Turkey.

BACKGROUND & OBJECTIVES: In this study, we aimed to investigate the relationship between serum TGF-ß1 and PDGF-B levels with the pathogenesis, clinical course and prognosis of adult Crimean-Congo hemorrhagic fever (CCHF) patients. METHODS: 50 adult patients and 30 healthy individuals as a control group were included in the study, who were followed up and treated with the diagnosis of CCHF at the Atatürk University Faculty of Medicine Infectious Diseases and Clinical Microbiology Clinic, between March 2017 and September 2019 in Eastern Anatolia Region in Turkey. Blood samples were taken from patients on the first day of their hospitalization and on the sixth day of their complaints. TGF-ß1 and serum PDGF-B levels were studied by ELISA method using commercial kits, from serum samples taken from CCHF patient group and individuals in healthy control group and stored at -80°C. RESULTS: While the serum TGF- ß1 levels of patients with CCHF were found to be significantly higher on the sixth day of their complaints compared to the first day of hospitalization (42.33 ± 15.42, 28.40 ± 7.06, p = 0.001, respectively), the serum PGDF-B levels were found to be significantly lower on the sixth day of their complaints compared to those measured on the day of hospitalization (62.14 ± 19.75, 93.96 ± 20.02, respectively, p = 0.001). INTERPRETATION & CONCLUSION: Serum TGF-ß1 levels are higher and PDGF-B levels are lower in CCHF patients with severe disease, indicating that serum TGF-ß1 and PDGF-B play an important role in the pathogenesis of CCHF.

Platelet-derived growth factor B attenuates lethal sepsis through inhibition of inflammatory responses.

Sepsis is a systemic inflammatory response during infection and remains a major clinical problem with high morbidity and mortality. Platelet-derived growth factor B (PDGF-B) is a member belongs to PDGF family and has been recently reported higher expressed in survivors of severe sepsis patients. However, the exact role and underlying mechanisms of PDGF-BB in sepsis remains unclear. In this study, we found that PDGF-BB levels were significantly elevated in patients with sepsis, and higher PDGF-BB levels were negatively correlated with the levels of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8), and chemokines (CXCL-1 and CCL2). PDGF-BB was also found increased in experimental sepsis in mice. Blockade of PDGF-BB using Tyrphostin AG 1296 aggravated, whereas recombinant PDGF-BB treatment improved survival and tissues injury in both two murine models of CLP-induced sepsis and LPS- induced endotoxemia. PDGF-BB blockade increased, whereas PDGF-BB administration decreased the inflammatory responses, as reflected by proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8), and chemokines (CXCL-1 and CCL2). PDGF-BB also showed inhibitory effect on immune cell activation and cytokines production in vivo and in vitro. Therefore, our findings suggest that PDGF-BB plays a protective role in sepsis by decreasing the production of pro-inflammatory cytokines and chemokines. PDGF-BB thus may be a potential therapeutic strategy for treating sepsis.

Circulating inflammation markers and prostate cancer.

BACKGROUND: Chronic inflammation is thought to influence the risk of prostate cancer. The purpose of this population-based case-control study was to evaluate the association of 48 circulating inflammation markers with prostate cancer, to identify candidate markers for further investigation. METHODS: Serum samples collected from 235 prostate cancer patients and 198 population-based controls recruited in Örebro County, Sweden, in 1989-1991, were assessed using a multiplex bead-based immunoassay to determine concentrations of 48 circulating inflammation markers. Logistic regression was first used to evaluate the association between individual markers (highest vs lowest concentration quartile) and prostate cancer in unadjusted and mutually adjusted models. Second, patients with inflammatory conditions, metastatic or advanced prostate cancer, were excluded to address the possible influence of systemic disease on inflammation markers. RESULTS: Individual analyses first identified 21 markers associated with prostate cancer (P < .05), which after mutual adjustment were reduced to seven markers. After the exclusion of men with conditions linked with systemic inflammation, associations between prostate cancer and deviant levels of C-X3-C motif chemokine ligand 1, platelet-derived growth factor subunit B homodimer, interleukin 10, C-C motif chemokine ligand (CCL) 21, and CCL11 remained statistically significant. CONCLUSIONS: In this explorative study, we identified candidate inflammation markers of possible importance for prostate cancer pathophysiology, for further evaluation in prospective studies.

Expression of platelet-derived growth factor B is upregulated in patients with thoracic aortic dissection.

OBJECTIVE: Thoracic aortic dissection (TAD) is a serious condition requiring urgent treatment to avoid catastrophic consequences. The inflammatory response is involved in the occurrence and development of TAD, possibly potentiated by platelet-derived growth factors (PDGFs). This study aimed to determine whether expression of PDGF-B (a subunit of PDGF-BB) was increased in TAD patients and to explore the factors responsible for its upregulation and subsequent effects on TAD. METHODS: Full-thickness ascending aorta wall specimens from TAD patients (n = 15) and control patients (n = 10) were examined for expression of PDGF-B and its receptor (PDGFRB) and in terms of morphology, inflammation, and fibrosis. Blood samples from TAD and control patients were collected to detect plasma levels of PDGF-BB and soluble elastins. RESULTS: Expression levels of PDGF-B, PDGFRB, and collagen I were significantly enhanced in ascending aorta wall specimens from TAD patients compared with controls. Furthermore, soluble elastic fragments and PDGF-BB were significantly increased in plasma from TAD patients compared with controls, and numerous irregular elastic fibers and macrophages were seen in the ascending aorta wall in TAD patients. CONCLUSIONS: An increase in elastic fragments in the aorta wall might be responsible for inducing the activation and migration of macrophages to injured sites, leading to elevated expression of PDGF-B, which in turn induces deposition of collagen, disrupts extracellular matrix homeostasis, and increases the stiffness of the aorta wall, resulting in compromised aorta compliance.

A biolayer interferometry-based enzyme-linked aptamer sorbent assay for real-time and highly sensitive detection of PDGF-BB.

Accurate, fast and sensitive detection of disease-specific protein biomarkers, especially in blood, urine, or other bodily fluids, is an important approach to achieve early disease diagnosis. Platelet-derived growth factor-BB (PDGF-BB), a widely used biomarker, is involved in a substantial number of serious diseases, such as hepatic fibrosis, atherosclerosis, age-related macular degeneration and diabetic eye disease and is often over-expressed in human malignant tumors. Therefore, the development of sensitive and specific detection methods for PDGF-BB is of great importance for the early diagnosis of disease and assessments of patient recovery. In the current study, a biolayer interferometry-based enzyme-linked aptamer sorbent assay (BLI-ELASA) was successfully established for rapid (20-25min), high-throughput (8 or 16 samples) and real-time monitoring of PDGF-BB in clinical samples. The method exhibited a broad detection range from 0.5 to 1000ng/mL of PDGF-BB (good linear range from 0.5 to 10ng/mL), with a low detection limit of 0.08ng/mL. Moreover, BLI-ELASA was applied to the detection of PDGF-BB in spiked serum and urine samples and showed a high degree of selectivity for PDGF-BB, good reproducibility, and stability. We believe that the methodology in this work can be easily adapted to detect other biomolecules in clinical samples, including viruses, pathogens and toxins, in a rapid, sensitive, high-throughput and real-time manner.

Differences in inflammatory marker patterns for adult community-acquired pneumonia patients induced by different pathogens.

INTRODUCTION: The inflammatory marker patterns of community-acquired Pneumonia (CAP) induced by different microorganisms in adult patients remained unclear. OBJECTIVES: We aim to explore the inflammatory marker patterns of adult CAP patients induced by different pathogens. METHODS: Adult CAP patients with definite etiologies were enrolled from September 2010 to June 2012. They were divided into three groups according to the causative pathogens: typical bacteria, Mycoplasma pneumoniae (MP), and viruses. Twenty-seven cytokines and bactericidal/permeability-increasing protein (BPI) levels of serum collected within 7 days onset in these groups were compared. RESULTS: One hundred twenty-four cases were enrolled for serum detection and analysis, including 10 typical bacterial pneumonia patients, 56 cases with MP pneumonia and 58 with viral pneumonia. Three kinds (PDGF-BB, IP-10, RANTES) of 27 cytokines and BPI levels were significantly elevated in patients with acute pneumonia than healthy controls. Distinct inflammatory marker patterns were released by different pathogens: typical bacterial pneumonia patients had highest levels of BPI, IL-6, IL-8, IL-1rα; while patients caused by MP presented higher levels of PDGF-BB, IL-17A, G-CSF than those caused by viruses. Rhinovirus owned a higher inflammatory response level than the other viruses. The area under the curve (AUC) of PDGF-BB to differentiate MP and virus infection was biggest, which was 0.708. CONCLUSION: Distinct inflammatory marker patterns were released by different pathogens during acute pneumonia. Significantly increased level of PDGF-BB was observed in acute pneumonia for the first time. It showed a better ability to differentiate MP and virus infection.

Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder.

Background: Autism spectrum disorders (ASDs) are complex, pervasive, and heterogeneous neurodevelopmental conditions with varying trajectories, significant male bias and largely unknown etiology. However, an understanding of the biological mechanisms driving pathophysiology is evolving. Immune system aberrations, as identified through cytokine profiles, are believed to have a role in ASD. Altered cytokine levels may facilitate identification of ASD subtypes as well as provide biological markers of response to effective treatments. Research exploring the relationship between cytokine profiles and ASD symptoms is, however, in its infancy. The objective of this study was to explore relationships between cytokine levels and the severity of ASD and other clinical traits. Methods: Multiplex assay techniques were used to measure levels of 27 cytokines in plasma samples from a cohort of 144 children diagnosed with ASD. Results: Overall, results showed a significant negative association between platelet-derived growth factor (PDGF)-BB, and the severity of ASD symptoms. Furthermore, a significant interaction with sex suggested a different immune profile for females compared to males. ASD symptom severity was negatively associated with levels of 4 cytokines, IL-1ß, IL-8, MIP-1ß, and VEGF, in females, but not in males. Conclusions: Results of the present study suggest that an altered cytokine response or profile is associated with the severity of ASD-related symptoms, with sex a potential modifier of this relationship. Further research in larger populations which recognizes the importance of sex comparisons and longitudinal assessments are now required to extend and further describe the role of the immune system in ASD.

[In vivo anti-tumor effect and in vitro anti-angiogenic effect of alcohol extract from Euphorbia prostrata].

The study was designed to investigate the anti-tumor and anti-angiogenic effects of alcohol extract from Euphorbia prostrata. The alcohol extract of E. prostrata was prepared, and the tolerated dosage was determined in mice by the test for acute toxicity. Then, MTT method was used to study the anti-proliferation effect of E. prostrata on normal cells and tumor cells. The rat aortic endothelial cells(RAECs) were primarily cultured. Subsequently, in vitro cell proliferation, migration and tubule formation assays were performed to detect the effect of alcohol extract of E. prostrata on proliferation, migration and angiogenesis. Western blot analysis was performed to detect the protein expressions of Akt, p-Akt, eNOS, p-eNOS, TGF-ß1 and Smad3 in RAECs treated with E. prostrata. In addition, an in vivo transplanted hepatocellular carcinoma model in nude mice was established to detect nude mass, tumor volume and tumor weight. The contents of vascular endothelial growth factor(VEGF) and the platelet-derived growth factor-BB(PDGF-BB) in blood serum were detected by using ELISA kits. HE staining was performed to study the morphology of tumor tissues. The tolerated dosage of alcohol extract of E. prostrata in mice was 94.29 g•kg⁻¹. Alcohol extract of E. prostrata showed no inhibitory effect on L6 cells, but significantly inhibited the proliferations of HepG-2, PC12, A549, and Hela cells with the following order： HepG-2>Hela>PC12>A549. Meanwhile, alcohol extract of E. prostrata markedly inhibited the proliferation, migration and tube formation of RAECs, and enhanced the expressions of phosphorylated Akt and eNOS and increased the expressions of TGF-ß1 and Smad3. In addition, E. prostrata notably inhibited the tumor growth in mice, and decreased the amount of VEGF, but increased the amount of PDGF-BB factor in serum of nude mice. The alcohol extract of E. prostrata may show an inhibitory effect on tumor growth and angiogenesis, which may contribute to its anti-tumor effect.

Correction of intermittent hypoxia reduces inflammation in obese subjects with obstructive sleep apnea.

BACKGROUND: In obese subjects with obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) may be linked to systemic and adipose tissue inflammation. METHODS: We obtained abdominal subcutaneous adipose tissue biopsies from OSA and non-OSA obese (BMI > 35) subjects at baseline and after 24 weeks (T1) of weight-loss intervention plus continuous positive airway pressure (c-PAP) or weight-loss intervention alone, respectively. OSA subjects were grouped according to good (therapeutic) or poor (subtherapeutic) adherence to c-PAP. RESULTS: At baseline, anthropometric and metabolic parameters, serum cytokines, and adipose tissue mRNA levels of obesity-associated chemokines and inflammatory markers were not different in OSA and non-OSA subjects. At T1, body weight was significantly reduced in all groups. Serum concentrations of IL-2, IL-4, IL-6, MCP-1, PDGFß, and VEGFα were reduced by therapeutic c-PAP in OSA subjects and remained unaltered in non-OSA and subtherapeutic c-PAP groups. Similarly, adipose tissue mRNA levels of macrophage-specific (CD68, CD36) and ER stress (ATF4, CHOP, ERO-1) gene markers, as well as of IL-6, PDGFß, and VEGFα, were decreased only in the therapeutic c-PAP group. CONCLUSION: CIH does not represent an additional factor increasing systemic and adipose tissue inflammation in morbid obesity. However, in subjects with OSA, an effective c-PAP therapy improves systemic and obesity-associated inflammatory markers. FUNDING: Ministero dell'Università e della Ricerca and Progetti di Rilevante Interesse Nazionale.

Proximity hybridization-mediated isothermal exponential amplification for ultrasensitive electrochemical protein detection.

In this study, we fabricated a novel electrochemical biosensing platform on the basis of target-triggered proximity hybridization-mediated isothermal exponential amplification reaction (EXPAR) for ultrasensitive protein analysis. Through rational design, the aptamers for protein recognition were integrated within two DNA probes. Via proximity hybridization principle, the affinity protein-binding event was converted into DNA assembly process. The recognition of protein by aptamers can trigger the strand displacement through the increase of the local concentrations of the involved probes. As a consequence, the output DNA was displaced, which can hybridize with the duplex probes immobilized on the electrode surface subsequently, leading to the initiation of the EXPAR as well as the cleavage of duplex probes. Each cleavage will release the gold nanoparticles (AuNPs) binding sequence. With the modification of G-quadruplex sequence, electrochemical signals were yielded by the AuNPs through oxidizing 3,3',5,5'-tetramethylbenzidine in the presence of H2O2. The study we proposed exhibited high sensitivity toward platelet-derived growth factor BB (PDGF-BB) with the detection limit of 52 fM. And, this method also showed great selectivity among the PDGF isoforms and performed well in spiked human serum samples.

Low plasma PDGF-BB levels are associated with estradiol in postmenopausal osteoporosis: PDGF-BB mediated by estradiol in women.

Objective This study aimed to investigate the association between low plasma Platelet-derived growth factor-BB (PDGF-BB) levels and oestradiol in Postmenopausal osteoporosis (PMOP). Methods This prospective study measured plasma PDGF-BB and oestradiol levels in outpatients who were admitted to our hospital. Participants were screened and then allocated to three groups: normal young women, postmenopausal control, and PMOP. Additionally, Sprague-Dawley rats underwent either sham surgery or bilateral ovariectomy (OVX), and were divided into the following groups: sham, OVX, OVX + oestradiol, and OVX + PDGF-BB. Plasma oestradiol and PDGF-BB levels were measured using commercially available ELISA kits. Results A total of 121 participants, including 69 normal young women, 28 patients with primary PMOP, and 24 age-matched postmenopausal women were enrolled. Plasma oestradiol and PDGF-BB levels were lower in postmenopausal women, especially in PMOP ( P < 0.01). Pearson correlations analysis showed that PDGF-BB levels were positively correlated with oestradiol levels and inversely correlated with age ( P < 0.01). The OVX rat model showed that oestradiol replacement increased plasma PDGF-BB levels, while PDGF-BB systematic treatment had no effect on plasma oestradiol levels. Conclusions Plasma PDGF-BB levels are maintained by oestrogen in normal young women and play a major role in PMOP.

Platelet lysate obtained via plateletpheresis performed in standing and awake equine donors.

BACKGROUND: Platelet preparations containing growth factors, attachment factors, and enzymes are appealing to enhance healing of injured tissues and as an alternative to xenogenic serum in cell culture media. Plateletpheresis is commonly used to collect platelets in human medicine but has not been validated in horses. STUDY DESIGN AND METHODS: Plateletpheresis to collect platelet concentrate was performed on six female, mixed breed, chemically restrained horses using commercially available apheresis equipment. Before and immediately after plateletpheresis, we performed physical examinations and collected blood for chemistry and coagulation panels and then again at 8, 16, 24, and 48 hours after the procedure. To produce platelet lysate, the platelet concentrate underwent two freeze-thaw cycles followed by centrifugation and filtration processing. The platelet lysate was then analyzed for cellular debris, fibrinogen, and growth factors. RESULTS: The collected platelet concentration contained a mean platelet yield of 390 × 103 /µL. Donor platelet count decreased from a mean of 193 × 103 /µL to 138 × 103 /µL after plateletpheresis, but no individual was at risk for hemorrhage. Pooled platelet lysate had minimal cellular residue and contained growth factor concentrations at 6.1 ng/mL for transforming growth factor-ß1, at 3.5 ng/mL for platelet-derived growth factor-BB, and at 13.8 ng/mL for vascular endothelial growth factor-A. CONCLUSION: Plateletpheresis using commercially available apheresis equipment is a feasible option for collecting platelet concentrate from equine donors. The lysate generated from the apheresis product contains growth factors and has potential to be used as a fetal bovine serum substitute for cell culture.

Excessive activation of the TLR9/TGF-ß1/PDGF-B pathway in the peripheral blood of patients with systemic lupus erythematosus.

BACKGROUND: Our aim is to study the existence of the TLR9/TGF-ß1/PDGF-B pathway in healthy humans and patients with systemic lupus erythematosus (SLE), and to explore its possible involvement in the pathogenesis of lupus nephritis (LN). METHODS: Protein levels of the cytokines were detected by ELISA. mRNA levels of the cytokines were analyzed by real-time PCR. MTT assay was used to test the proliferation of mesangial cells under different treatments. RESULTS: Compared to healthy controls (N Control = 56), levels of Toll-like receptor (TLR)9, transforming growth factor (TGF)-ß1, and platelet-derived growth factor B (PDGF-B) were increased significantly in the peripheral blood of SLE patients (N SLE = 112). Significant correlations between the levels of TLR9, TGF-ß1, and PDGF-B were observed in both healthy controls and SLE patients. The levels of TGF-ß1 and PDGF-B were greatly enhanced by TLR9 activation in primary cell cultures. The proliferation of mesangial cells induced by the plasma of SLE patients was significantly higher than that induced by healthy controls; PDGF-B was involved in this process. The protein levels of PDGF-B homodimer correlated with the levels of urine protein in SLE patients with LN (N LN =38). CONCLUSIONS: The TLR9/TGF-ß1/PDGF-B pathway exists in humans and can be excessively activated in SLE patients. High levels of PDGF-B may result in overproliferation of mesangial cells in the kidney that are involved in the development of glomerulonephritis and LN. Further studies are necessary to identify TLR9, TGF-ß1, and PDGF-B as new therapeutic targets to prevent the development of glomerulonephritis and LN.

Platelet-derived growth factor A mRNA in platelets is associated with the degree of hepatic fibrosis in chronic hepatitis C.

INTRODUCTION:: Transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF) are the main cytokines related to hepatic fibrogenesis. METHODS:: RNA isolated from the platelets and hepatic tissue of 43 HCV carriers was used for quantitative polymerase chain reaction to determine TGFB1, PDGFA, and PDGFB RNA expression. RESULTS:: The mRNA expression of PDGFA in platelets was significantly lower in the group with advanced fibrosis than in the group with early-stage fibrosis. TGFB1 was more frequently expressed in platelets than in hepatic tissue, which was different from PDGFB. CONCLUSIONS:: A pathway mediated by overexpression of TGFB1 via PDGFA in megakaryocytes could be involved in the development of fibrosis.

Validation of commercial ELISAs for quantifying anabolic growth factors and cytokines in canine ACD-A anticoagulated plasma.

Platelet-rich plasma has been studied extensively in dogs, but validation of enzyme-linked immunosorbent assays (ELISAs) for quantifying anabolic growth factors and inflammatory cytokines in canine plasma prepared with citrate-based anticoagulants is not available. We performed a validation of commercial ELISAs for transforming growth factor-beta 1 (TGF-ß1), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) for use with canine plasma prepared with acid-citrate-dextrose, solution A (ACD-A). Platelet-poor plasma (PPP) anticoagulated with ACD-A as well as PPP anticoagulated with ACD-A and spiked with the relevant canine recombinant proteins were evaluated with each ELISA to calculate the efficiency of spike recovery. Replicates of the spiked PPP were also assessed in 2 additional assays to quantify intra-assay and interassay precision. The efficiency of spike recovery was within 75-125% of the expected concentration for the TGF-ß1, PDGF-BB, and VEGF ELISAs. The intra- and interassay variability were <25% for the TGF-ß1, PDGF-BB, VEGF, and TNF-α ELISAs. The TGF-ß1, PDGF-BB, and VEGF ELISAs demonstrate acceptable efficiency of spike recovery and intra- and interassay variability, whereas the TNF-α and IL-1ß ELISAs did not meet industry standards of performance with ACD-A anticoagulated canine plasma.

Platelet-derived growth factor A mRNA in platelets is associated with the degree of hepatic fibrosis in chronic hepatitis C

Abstract: INTRODUCTION: Transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF) are the main cytokines related to hepatic fibrogenesis. METHODS: RNA isolated from the platelets and hepatic tissue of 43 HCV carriers was used for quantitative polymerase chain reaction to determine TGFB1, PDGFA, and PDGFB RNA expression. RESULTS: The mRNA expression of PDGFA in platelets was significantly lower in the group with advanced fibrosis than in the group with early-stage fibrosis. TGFB1 was more frequently expressed in platelets than in hepatic tissue, which was different from PDGFB. CONCLUSIONS: A pathway mediated by overexpression of TGFB1 via PDGFA in megakaryocytes could be involved in the development of fibrosis.

Enhanced electrogenerated chemiluminescence behavior of C3N4 QDs@ C3N4 nanosheet and its signal-on aptasensing for platelet derived growth factor.

A novel g-C3N4 nanosheets embedded with C3N4 QDs nanocomposites (QD@CNNS) was prepared by simple oxidation using hydrogen peroxide and UV light irradiation. This nanocomposite exhibits more stable and stronger electrochemiluminescent (ECL) behavior compared with CNNS. Coupling this nanocomposite with Fc-labeled aptamer, a signal-on aptasensor for platelet derived growth factor BB (PDGF-BB) is fabricated. Initially, the Fc-labeled aptamer binds onto QD@CNNS via π-π conjugation and electrostatic interaction, quenching ECL emission from QD@CNNS. The introduction of target efficiently recovers the ECL signal by the formation of PDGF-BB/aptamer complex. The ECL intensity is proportion to the concentration of PDGF-BB in the range of 0.02-80nM with a detection limit of 0.013nM. This work demonstrates a simple synthesis method to obtain QD@CNNS with excellent ECL behavior, and opens up the application of g-C3N4 nanocomposite in signal-on aptasensing.

Carbon-based nanocomposites with aptamer-templated silver nanoclusters for the highly sensitive and selective detection of platelet-derived growth factor.

We synthesized two kinds of carbon-based nanocomposites of silver nanoclusters (AgNCs). An aptamer for targeted platelet-derived growth factor-BB (PDGF-BB) detection was used as the organic phase to produce AgNCs@Apt, three dimensional reduced graphene oxide@AgNCs@Aptamer (3D-rGO@AgNCs@Apt), and graphene quantum dots@AgNCs@Aptamer (GQD@AgNCs@Apt) nanocomposites. The formation mechanism of the developed nanocomposites was described by detailed characterizations of their chemical and crystal structures. Subsequently, the as-synthesized nanoclusters containing aptamer strands were applied as the sensitive layers to fabricate a novel electrochemical aptasensor for the detection of PDGF-BB, which may be directly used to determine the target protein. Electrochemical impedance spectra showed that the developed 3D-rGO@AgNCs@Apt-based biosensor exhibited the highest sensitivity for PDGF-BB detection among three kinds of fabricated aptasensors, with an extremely low detection limit of 0.82pgmL-1. In addition, the 3D-rGO@AgNCs@Apt-based biosensor showed high selectivity, stability, and applicability for the detection of PDGF-BB. This finding indicated that the AgNC-based nanocomposites prepared by a one-step method could be used as an electrochemical biosensor for various detection procedures in the biomedical field.

Predicting neurological deficit severity due to subarachnoid haemorrhage: soluble CD40 ligand and platelet-derived growth factor-BB.

BACKGROUND: Several biological markers can predict outcomes in patients with subarachnoid haemorrhage (SAH), but markers to predict neurological deficit severity in patients with SAH and poor neurological condition have not yet been established. Soluble CD40 ligand (sCD40L) and platelet-derived growth factor (PDGF) are related to the systemic inflammatory response. OBJECTIVE: In a prospective study, to investigate the relationship between clinical outcomes and blood test results in patients with SAH and severe neurological deficits. METHODS: We studied 17 patients with Hunt and Hess Grade IV and Fisher Class III neurological deficits who had undergone aneurysmal clipping within 48 hours of onset of SAH. We measured their levels of sCD40L, PDGF-AA, PDGF-AB, PDGF-BB and C-reactive protein (CRP), their white blood cell (WBC) and platelet counts and their body temperature. Blood tests were performed at an early time point (Day 0, the day of the SAH before craniotomy) and at a late time point (Day 10). The modified Rankin Scale (mRS) score of the patients was assessed at Day 60. RESULTS: Seven patients (41%) were classified as mRS 0-2 (good outcome) and 10 (59%) as mRS 3-5 (poor outcome). The blood levels of sCD40L (P = 0.05), PDGF-BB (P = 0.02) and CRP (P = 0.02), WBC count (P = 0.005) and body temperature (P = 0.01) at the late time point were significantly higher in patients with poor outcomes than in patients with good outcomes. CONCLUSION: Our data suggest that sCD40L, PDGF-BB, WBC count, CRP and body temperature can predict the neurological outcome in patients with SAH and poor neurological condition.

PDGFB, a new candidate plasma biomarker for venous thromboembolism: results from the VEREMA affinity proteomics study.

There is a clear clinical need for high-specificity plasma biomarkers for predicting risk of venous thromboembolism (VTE), but thus far, such markers have remained elusive. Utilizing affinity reagents from the Human Protein Atlas project and multiplexed immuoassays, we extensively analyzed plasma samples from 2 individual studies to identify candidate protein markers associated with VTE risk. We screened plasma samples from 88 VTE cases and 85 matched controls, collected as part of the Swedish "Venous Thromboembolism Biomarker Study," using suspension bead arrays composed of 755 antibodies targeting 408 candidate proteins. We identified significant associations between VTE occurrence and plasma levels of human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1), von Willebrand factor (VWF), glutathione peroxidase 3 (GPX3), and platelet-derived growth factor ß (PDGFB). For replication, we profiled plasma samples of 580 cases and 589 controls from the French FARIVE study. These results confirmed the association of VWF and PDGFB with VTE after correction for multiple testing, whereas only weak trends were observed for HIVEP1 and GPX3. Although plasma levels of VWF and PDGFB correlated modestly (ρ ∼ 0.30) with each other, they were independently associated with VTE risk in a joint model in FARIVE (VWF P < .001; PDGFB P = .002). PDGFΒ was verified as the target of the capture antibody by immunocapture mass spectrometry and sandwich enzyme-linked immunosorbent assay. In conclusion, we demonstrate that high-throughput affinity plasma proteomic profiling is a valuable research strategy to identify potential candidate biomarkers for thrombosis-related disorders, and our study suggests a novel association of PDGFB plasma levels with VTE.