Suppression of Mannheimia (Pasteurella) haemolytica serovar 1 infection in lambs by intrapulmonary administration of ovine antimicrobial anionic peptide

In this study, the efficacy of ovine antimicrobial anionic peptide (AP) was assessed in a lamb model of acute pneumonia. A single intratracheal dose of the peptide, H-DDDDDDD-OH (0.5 mg) reduced pulmonary inflammation and the concentration of Mannheimia (Pasteurella) haemolytica in infected lung tissue. Administration of H-DDDDDDD-OH after infection was more effective in reducing the consolidation and lesion scores at the deposition site than its administration prior to infection. Hence, the in vivo effectiveness of AP suggests that it may have applications in the treatment of pulmonary infections. Further studies are needed to confirm these findings and also to determine the optimal doses and intervals of H-DDDDDDD-OH therapy

RGD constructs with physical anchor groups as polymer co-electrospinnable cell adhesives

The tissue integration of synthetic polymers can be promoted by displaying RGD peptides at the biointerface with the objective of enhancing colonization of the material by endogenous cells. A firm but flexible attachment of the peptide to the polymer matrix, still allowing interaction with receptors, is therefore of interest. Here, the covalent coupling of flexible physical anchor groups, allowing for temporary immobilization on polymeric surfaces via hydrophobic or dipole–dipole interactions, to a RGD peptide was investigated. For this purpose, a stearate or an oligo(ethylene glycol) (OEG) was attached to GRGDS in 51–69% yield. The obtained RGD linker constructs were characterized by NMR, IR and MALDI-ToF mass spectrometry, revealing that the commercially available OEG and stearate linkers are in fact mixtures of similar compounds. The RGD linker constructs were co-electrospun with poly(p-dioxanone) (PPDO). After electrospinning, nitrogen could be detected on the surface of the PPDO fibers by X-ray photoelectron spectroscopy. The nitrogen content exceeded the calculated value for the homogeneous material mixture suggesting a pronounced presentation of the peptide on the fiber surface. Increasing amounts of RGD linker constructs in the electrospinning solution did not lead to a detection of an increased amount of peptide on the scaffold surface, suggesting inhomogeneous distribution of the peptide on the PPDO fiber surface. Human adipose-derived stem cells cultured on the patches showed similar viability as when cultured on PPDO containing pristine RGD. The fully characterized RGD linker constructs could serve as valuable tools for the further development of tissue-integrating polymeric scaffolds

The impact of COVID-19 on research

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Coronavirus disease 2019 (COVID-19) has swept across the globe causing hundreds of thousands of deaths, shutting down economies, closing borders and wreaking havoc on an unprecedented scale. It has strained healthcare services and personnel to the brink in many regions and will certainly deeply mark medical research both in the short and long-term

The influence of electrospinning parameters on polydioxanone scaffold properties

Conduits currently used to reconstruct the right ventricular outflow tract (RVOT) have no growth potential and require reoperations, resulting in an increased level of morbidity and mortality. This work investigates the effect of electrospinning parameters on the mechanical properties and biocompatibility of bioresorbable tubular scaffolds, as part of a program to develop a tissue-engineered valved tube for RVOT replacement. Electrospinning was used to develop tubular scaffolds of polydioxanone, with the experimental parameters systematically varied. Three electrospinning parameters (volume of liquid, flow rate, and speed of mandrel rotation) were investigated, and their effects on the mechanical properties and cellular response of the scaffolds were analysed using scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, gas chromatography, uniaxial tensile tests, cell viability and cytotoxicity assays. Mechanical properties were compared to those of the native RVOT reported in the literature. Increasing the mandrel rotation speed tended to increase fibre alignment slightly, and led to more profound rises in the stress at failure and Young's modulus. An increase in flow rate also increased the rigidity of the tubes. Cell viability and cytotoxicity assays showed all the tubes produced to have excellent biocompatibility. Through variation of the processing parameters, it is possible to tune mechanical properties of medical-grade polymer tubes over a wide range. By using a mandrel rotation speed of 50 rpm and a flow rate of 20 mL/h or higher we can prepare materials with Young's modulus, strain at failure, and tensile stress close to the native tissue. Electrospinning therefore offers great promise in the development of scaffolds to match the properties of the native RVOT, paving the way to a future bioresorbable device to replace the RVOT in children

The battle between fake news and science

Fake news is fabricated information that mimics news media content yet lacks the editorial norms and processes that ensure accuracy and credibility [ [1] ]. This includes misinformation (misleading information) and disinformation (false information purposely spread to deceive people)

Polymer-Based Reconstruction of the Inferior Vena Cava in Rat: Stem Cells or RGD Peptide?

As part of a program targeted at developing a resorbable valved tube for replacement of the right ventricular outflow tract, we compared three biopolymers (polyurethane [PU], polyhydroxyalkanoate (the poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxyvalerate) [PHBVV]), and polydioxanone [PDO]) and two biofunctionalization techniques (using adipose-derived stem cells [ADSCs] or the arginine-glycine-aspartate [RGD] peptide) in a rat model of partial inferior vena cava (IVC) replacement. Fifty-three Wistar rats first underwent partial replacement of the IVC with an acellular electrospun PDO, PU, or PHBVV patch, and 31 nude rats subsequently underwent the same procedure using a PDO patch biofunctionalized either by ADSC or RGD. Results were assessed both in vitro (proliferation and survival of ADSC seeded onto the different materials) and in vivo by magnetic resonance imaging (MRI), histology, immunohistochemistry [against markers of vascular cells (von Willebrand factor [vWF], smooth muscle actin [SMA]), and macrophages ([ED1 and ED2] immunostaining)], and enzyme-linked immunosorbent assay (ELISA; for the expression of various cytokines and inducible NO synthase). PDO showed the best in vitro properties. Six weeks after implantation, MRI did not detect significant luminal changes in any group. All biopolymers were evenly lined by vWF-positive cells, but only PDO and PHBVV showed a continuous layer of SMA-positive cells at 3 months. PU patches resulted in a marked granulomatous inflammatory reaction. The ADSC and RGD biofunctionalization yielded similar outcomes. These data confirm the good biocompatibility of PDO and support the concept that appropriately peptide-functionalized polymers may be successfully substituted for cell-loaded materials

The orchestration of gene expression and the editing role of microRNA

In this short educational communication the ESPU Research Committee presents the role of non-coding RNA and how these can affect gene expression. In particular we discuss the role of microRNA on post transcriptional changes and how these may cause pathological conditions within Pediatric Urology and how microRNA could be useful in future clinical practice