Periostin identified as a potential biomarker of prostate cancer by iTRAQ-proteomics analysis of prostate biopsy

<p>Abstract</p> <p>Background</p> <p>Proteomics may help us better understand the changes of multiple proteins involved in oncogenesis and progression of prostate cancer(PCa) and identify more diagnostic and prognostic biomarkers. The aim of this study was to screen biomarkers of PCa by the proteomics analysis using isobaric tags for relative and absolute quantification(iTRAQ).</p> <p>Methods</p> <p>The patients undergoing prostate biopsies were classified into 3 groups according to pathological results: benign prostate hyperplasia (BPH, n = 20), PCa(n = 20) and BPH with local prostatic intraepithelial neoplasm(PIN, n = 10). Then, all the specimens from these patients were analyzed by iTRAQ and two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS). The Gene Ontology(GO) function and the transcription regulation networks of the differentially expressed were analyzed by MetaCore software. Western blotting and Immunohistochemical staining were used to analyze the interesting proteins.</p> <p>Result</p> <p>A total of 760 proteins were identified from 13787 distinct peptides, including two common proteins that enjoy clinical application: prostate specific antigen (PSA) and prostatic acid phosphatase(PAP). Proteins that expressed differentially between PCa and BPH group were further analyzed. Compared with BPH, 20 proteins were significantly differentially up-regulated (>1.5-fold) while 26 were significantly down-regulated in PCa(<0.66-fold). In term of GO database, the differentially expressed proteins were divided into 3 categories: cellular component(CC), molecular function (MF) and biological process(BP). The top 5 transcription regulation networks of the differentially expressed proteins were initiated through activation of SP1, p53, YY1, androgen receptor(AR) and c-Myc The overexpression of periostin in PCa was verified by western blotting and immunohistochemical staining.</p> <p>Conclusion</p> <p>Our study indicates that the iTRAQ technology is a new strategy for global proteomics analysis of the tissues of PCa. A significant up-regulation of periostin in PCa compared to BPH may provide clues for not only a promising biomarker for the prognosis of PCa but also a potential target for therapeutical intervention.</p

Aerodynamic analysis of a flapping wing aircraft for short landing

An investigation into the aerodynamic characteristics has been presented for a bio-inspired flapping wing aircraft. Firstly, a mechanism has been developed to transform the usual rotation powered by a motor to a combined flapping and pitching motion of the flapping wing. Secondly, an experimental model of the flapping wing aircraft has been built and tested to measure the motion and aerodynamic forces produced by the flapping wing. Thirdly, aerodynamic analysis is carried out based on the measured motion of the flapping wing model using an unsteady aerodynamic model (UAM) and validated by a computational fluid dynamics (CFD) method. The difference of the average lift force between the UAM and CFD method is 1.3%, and the difference between the UAM and experimental results is 18%. In addition, a parametric study is carried out by employing the UAM method to analyze the effect of variations of the pitching angle on the aerodynamic lift and drag forces. According to the study, the pitching amplitude for maximum lift is in the range of 60°~70° as the flight velocity decreases from 5 m/s to 1 m/s during landing

Design and experiment of a bionic flapping wing mechanism with flapping–twist–swing motion based on a single rotation

In the present study, a bionic flapping mechanism of a spatial six-bar configuration was designed to transform a single rotation of a motor into a three degrees of freedom “flapping–twist–swing” cooperative motion of a flapping wing. The kinematics model of the flapping mechanism movement was constructed. The flapping trajectory of the wing based on the kinematics model was to mimic the motion of a pigeon wing in landing flight. To reduce the manufacturing complexity, the flapping mechanism was simplified with only two degrees of freedom (flapping and twist) retained. Finally, a prototype model with a 0.9 m wing span was built and tested. A comparison among the experimental data, theoretical calculation results, and ADAMS simulation results revealed that the difference in the flapping and the twist amplitude between experimental observations and theoretical calculation results was 12.5% and 2.3%, respectively. This was owing to the elastic deformation of the bar and the mechanism simplification. The comparison results also indicated that the maximum difference in the inertial force was 5.9% in up-stroke and 6.7% in down-stroke, respectively. The experimental results showed that the inertial force of the model with the wing patagium was approximately 2.2 N, and the maximum positive and negative lift was 2.1 N and −1.5 N, respectively. It is hoped that this study can provide guidance for the design of bionic flapping wing mechanisms of a flapping wing aircraft for short landing flight

The method evaluation of culturing df-1 to proliferate canine distemper virus in mink with cephodex microcarrier

As an acute and highly lethal infectious disease, there is no specific therapeutic drug for canine distemper (CD). Although the process of large-scale production of canine distemper virus (CDV) vaccine of mink has been greatly improved, there are still many deficiencies to be perfected. As one of the most promising technologies for large-scale vaccine production, microcarrier suspension culture technology needs to be further improved. In this study, the application effect of the new Cephodex microcarrier in CDV culture was evaluated to establish a set of technical process for DF-1 cell high-density growth and CDV efficient proliferation. To perfect the large-scale CDV production process, Cephodex was used to suspension culture DF-1 cells for proliferating CDV. In a shake flasks culture system, the optimal culture conditions were established by optimizing culture temperature, virus inoculation and harvest time. Therefore, mink CD vaccine high-efficiency production was laid on the preliminarily established technology of CDV microcarrier suspension culture. The cell density could reach over 3×106 cells/mL after 72 h cultured with Cephodex microcarrier at 37°C. Proliferated at 35°C, the CDV titer after 72 h was about 100.5 TCID50/0.1ml higher than that at 33°C and 37°C. These results show that the Cephodex microcarrier could be used for large-scale culture of DF-1 cells and efficient proliferation of CDV

Knee osteoarthritis pendulum therapy : in vivo evaluation and a randomised, single-blind feasibility clinical trial

Background. Exercise is recommended as the first-line management for knee osteoarthritis (KOA); however, it is difficult to determine which specific exercises are more effective. This study aimed to explore the potential mechanism and effectiveness of a leg-swinging exercise practiced in China, called ‘KOA pendulum therapy’ (KOAPT). Intraarticular hydrostatic and dynamic pressure (IHDP) are suggested to partially explain the signs and symptoms of KOA. As such this paper set out to explore this mechanism in vivo in minipigs and in human volunteers alongside a feasibility clinical trial. The objective of this study is 1) to analyze the effect of KOAPT on local mechanical and circulation environment of the knee in experimental animals and healthy volunteers; and 2) to test if it is feasible to run a large sample, randomized/single blind clinical trial. Methods. IHDP of the knee was measured in ten minipigs and ten volunteers (five healthy and five KOA patients). The effect of leg swinging on synovial blood flow and synovial fluid content depletion in minipigs were also measured. Fifty KOA patients were randomly divided into two groups for a feasibility clinical trial. One group performed KOAPT (targeting 1000 swings/leg/day), and the other performed walking exercise (targeting 4000 steps/day) for 12 weeks with 12 weeks of follow-up. Results. The results showed dynamic intra-articular pressure changes in the knee joint, increases in local blood flow, and depletion of synovial fluid contents during pendulum leg swinging in minipigs. The intra-articular pressure in healthy human knee joints was −11.32 ± 0.21 (cmH2O), whereas in KOA patients, it was −3.52 ± 0.34 (cmH2O). Measures were completed by 100% of participants in all groups with 95–98% adherence to training in both groups in the feasibility clinical trial. There were significant decreases in the Oxford knee score in both KOAPT and walking groups after intervention (p < 0.01), but no significant differences between the two groups. Conclusion. We conclude that KOAPT exhibited potential as an intervention to improve symptoms of KOA possibly through a mechanism of normalising mechanical pressure in the knee; however, optimisation of the method, longer-term intervention and a large sample randomized-single blind clinical trial with a minimal 524 cases are needed to demonstrate whether there is any superior benefit over other exercises

Safety and Efficacy of Low-Dose Tirofiban Combined With Intravenous Thrombolysis and Mechanical Thrombectomy in Acute Ischemic Stroke: A Matched-Control Analysis From a Nationwide Registry

Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p &gt; 0.05). Similar results were obtained after propensity score matching.Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy