Poly(2-oxazoline)s are emerging revolutionary biomaterials, exhibiting comparable and even superior properties to well-established counterparts. Overcoming current tedious wet synthesis methods, we ...report solvent-free and substrate independent, plasma polymerised nanoscale biocompatible polyoxazoline coatings capable of controlling protein and cell adhesion, and significantly reducing biofilm build up.
Prostate cancer cells frequently overexpress the gastrin-releasing peptide receptor, and various strategies have been applied in preclinical settings to target this receptor for the specific delivery ...of anticancer compounds. Recently, elastin-like polypeptide (ELP)-based self-assembling micelles with tethered GRP on the surface have been suggested to actively target prostate cancer cells. Poorly soluble chemotherapeutics such as docetaxel (DTX) can be loaded into the hydrophobic cores of ELP micelles, but only limited drug retention times have been achieved. Herein, we report the generation of hybrid ELP/liposome nanoparticles which self-assembled rapidly in response to temperature change, encapsulated DTX at high concentrations with slow release, displayed the GRP ligand on the surface, and specifically bound to GRP receptor expressing PC-3 cells as demonstrated by flow cytometry. This novel type of drug nanocarrier was successfully used to reduce cell viability of prostate cancer cells in vitro through the specific delivery of DTX.
Summary
Objective
Corticosteroid‐binding globulin (CBG) is cleaved by neutrophil elastase converting the high‐affinity (haCBG) conformation of CBG to a low‐affinity (laCBG) conformation with a ...ninefold reduced cortisol‐binding affinity. These in vitro data suggest that cortisol release by CBG cleavage results in the targeted delivery of cortisol to areas of inflammation. Our objective was to determine whether CBG cleavage alters circulating levels of haCBG and laCBG in vivo in proportion to sepsis severity.
Design
Prospective, observational cohort study in an adult tertiary level Intensive Care Unit in Adelaide, Australia.
Patients
Thirty‐three patients with sepsis or septic shock grouped by illness severity sepsis, septic shock survivors, septic shock nonsurvivors and other shock.
Measurements
Plasma levels of haCBG and laCBG were assessed using a recently developed in‐house assay in patients. Plasma total and free cortisol levels were also measured.
Results
Plasma total CBG and haCBG levels fell significantly, in proportion to disease severity (P < 0·0001 for both). There was a nonsignificant increase in free and total cortisol as illness severity worsened (P = 0·19 and P = 0·39, respectively). Illness severity was better correlated with haCBG levels than either free or total cortisol levels.
Conclusions
Increasing illness severity in sepsis and septic shock is associated with markedly reduced circulating haCBG concentrations in vivo. We propose that low levels of haCBG in chronic inflammation may limit the availability of cortisol to inflammatory sites, perpetuating the inflammatory process.
The causal association of Zika virus (ZIKV) with microcephaly, congenital malformations in infants, and Guillain-Barré syndrome in adults highlights the need for effective vaccines. Thus far, efforts ...to develop ZIKV vaccines have focused on the viral envelope. ZIKV NS1 as a vaccine immunogen has not been fully explored, although it can circumvent the risk of antibody-dependent enhancement of ZIKV infection, associated with envelope antibodies. Here, we describe a novel DNA vaccine encoding a secreted ZIKV NS1, that confers rapid protection from systemic ZIKV infection in immunocompetent mice. We identify novel NS1 T cell epitopes in vivo and show that functional NS1-specific T cell responses are critical for protection against ZIKV infection. We demonstrate that vaccine-induced anti-NS1 antibodies fail to confer protection in the absence of a functional T cell response. This highlights the importance of using NS1 as a target for T cell-based ZIKV vaccines.
In mammals the pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP) are important components of the immune response. Although pentraxins have been isolated from a number of fish ...species few studies detail their functional immunological role. In this paper we report the establishment of a flow cytometry based assay to measure the phagocytic activity of isolated snapper head kidney leukocytes (HKLs). This assay was then used to examine the ability of a pentraxin-like protein isolated from the serum of snapper (
P. auratus) (Sn-PLP) to act as an opsonin. Incubation of snapper head kidney leukocytes (HKL) with FITC-labelled beads resulted in uptake of these particles by approximately 35% of HKLs. Incubation of beads with Sn-PLP enhanced phagocytosis by snapper HKLs in a dose-dependant manner. Enhanced phagocytosis could be inhibited by addition of a rabbit anti-Sn-PLP antibody suggesting that Sn-PLP may act as a ligand for a HKL cell surface receptor. This study provides further evidence toward a functional role for pentraxins in the host defence repertoire of fish.
This study investigated the effects of prolonged administration of a commercial β-glucan based immunostimulant preparation, EcoActiva™, in the form of a feed supplement, on non-specific immune ...parameters and the growth rate of snapper (Pagrus auratus). Fish held at a temperature representing either summer or winter conditions, were sampled periodically and assayed for head kidney macrophage activity via in vitro superoxide production, and classical and alternative complement activity. Fish were also weighed monthly and the growth rate determined. Fish fed on a diet supplemented with EcoActiva™ and held at the winter temperature had a significant enhancement of macrophage superoxide anion production upon stimulation with phorbol myristate acetate (PMA), and this increased activity was maintained throughout the trial. Macrophage activity in fish fed the supplemented diet and held at the summer temperature was also increased. However, EcoActiva™ failed to increase either classical or alternate complement activity. Most significantly EcoActiva™ resulted in an increase in growth rates of the fish held at the winter temperature as compared to the control fish, although no difference was seen between the groups held at the summer temperature. These results suggest that routine incorporation of β-glucan preparations like EcoActiva™during winter may enhance macrophage function and growth rates at a time of increased disease susceptibility and little or no growth.
We report on a platform for extended release of biologically-active therapeutic antibodies. Extended antibody release has been achieved by utilising a plasma polymer film of controlled and ...predetermined thickness deposited on the top of a porous platform loaded with rituximab. Antibody release kinetics directly correlates to the plasma polymer film thickness that is in turn controlled by the plasma polymer deposition time. After 1 month, 82%, 60% and 45% of the antibody is released from platforms coated with plasma polymer for 50s, 150s and 300s, respectively. Activity of the released antibody was assessed in cultures of CD20-positive Daudi cells by using polyacrylamide gel electrophoresis and flow cytometry. The results from gel electrophoresis and flow cytometry indicate that the antibody had maintained its integrity during the release process. This work provides a proof-of-concept technology that achieves extended release of biologically active rituximab for more than 30 days.
•A proof of concept of novel therapeutic device for release of active therapeutic antibodies is presented.•Extended and controlled release for 30 days is demonstrated.•Biological activity of the released antibody is demonstrated in cell culture.
This study investigated the in vitro effects of a commercial β-glucan preparation, EcoActiva™, on the respiratory burst activity of head-kidney macrophages isolated from pink snapper (Pagrus ...auratus), a marine fish cultured in Australia. Macrophages incubated with EcoActiva™ displayed morphological characteristics of activation, and were stimulated to produce superoxide. Pre-incubation with low levels of EcoActiva™ significantly increased the response to phorbol myristate acetate (PMA) and lipopolysaccharide (LPS), indicating that EcoActiva™ could prime these macrophages. Co-culturing macrophages with both LPS and PMA, or EcoActiva™ and PMA, increased burst activity compared with the response to PMA alone, however, this increase was additive and not synergistic. These results suggest that EcoActiva™ is able to stimulate non-specific immunity in snapper through increased respiratory burst activity of macrophages, an important component of the host defence network.
Pentraxin-like molecules have been isolated from a number of fish species. However, little is known about the function of these proteins in the teleosts. In this study we report the isolation and ...characterization of a pentraxin-like molecule from the serum of snapper (
Pagrus auratus) that has the ability to activate complement. This pentraxin-like protein was isolated from serum by calcium-dependent binding to agarose. SDS–PAGE analysis demonstrated an oligomeric protein of approximately 200
kDa consisting of non-covalently bound subunits of 26 and 23
kDa. Protein sequencing revealed significant (50%) sequence identity with pentraxins from both Atlantic salmon (
S. salar) and rainbow trout (
O. mykiss). However, polyclonal antibodies raised against snapper pentraxin did not recognise salmon or trout pentraxin in Western blot analysis. Following LPS injection, snapper pentraxin levels increased 2-fold before gradually returning to basal levels. Most significantly, the isolated pentraxin initiated complement-mediated lysis of ligand-coated sheep erythrocytes in a dose-dependent fashion. In view of the similarity between the known fish pentraxins, and their similarity to mammalian serum amyloid P-components we conclude that the isolated protein may be a snapper pentraxin homologue.
Due to the favorable properties of graphene quantum dots (GQDs), there has been a rapid development of sensors, devices, and composite materials, which incorporate this 0D nanomaterial. GQDs provide ...a means to instill superior optical, electronic, mechanical, and adsorptive properties to various platforms and have found use as biosensors, photovoltaic devices, polymer composites, and drug delivery vehicles. One of the key factors to successfully integrating GQD technology is the intelligent choice of synthetic chemical pathways to fabricate, modify, and instill functionality in the developed platform. GQDs are decorated with a variety of functional groups that are amenable to traditional synthetic chemistry transformations; however, the technology for post‐synthetic modifications is only in its infancy. Herein, a comprehensive analysis of the chemistry available for modifying GQDs is provided; starting from methods for GQD fabrication and synthetic chemical pathways for producing functional GQDs, to the advantages, disadvantages, and challenges of specific chemistries, and finally techniques for the appropriate characterization of these functional materials. This review is meant for researchers considering entering the GQD field, as well as those more experienced, providing a practical guide on how to prepare, modify, and characterize GQDs for a broad range of applications.
This review provides a comprehensive overview and practical guide on the fabrication, synthetic modification, and characterization of graphene quantum dots (GQDs). The increasing level of complexity and functionality of materials and devices that utilize GQDs is driving the need for elaborate and precise modification of this nanomaterial.
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