Gyrospun antimicrobial nanoparticle loaded fibrous polymeric filters

© 2016 The Authors. Published by Elsevier B.V. © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).A one step approach to prepare hybrid nanoparticle embedded polymer fibres using pressurised gyration is presented. Two types of novel antimicrobial nanoparticles and poly (methylmethacrylate) polymer were used in this work. X-ray diffraction analysis of the nanoparticles revealed Ag, Cu and W are the main elements present in them. The concentration of the polymer solution and the nanoparticle concentration had a significant influence on the fibre diameter, pore size and morphology. Fibres with a diameter in the range of 6-20 ìm were spun using 20 wt% polymer solutions containing 0.1, 0.25 and 0.5 w% nanoparticles under 0.3 MPa working pressure and a rotational speed of 36000 rpm. Continuous, bead-free fibre morphologies were obtained for each case. The pore size in the fibres varied between 36-300 nm. Successful incorporation of the nanoparticles in polymer fibres was confirmed by energy dispersive x-ray analysis. The fibres were also gyrospun on to metallic disks to prepare filters which were tested for their antibacterial activity on a suspension of Pseudomonas aeruginosa. Nanoparticle loaded fibres showed higher antibacterial efficacy than pure poly(methylmethacrylate) fibres.8pÍuPeer reviewedFinal Published versio

Pharmacological strategies to reduce anthracycline-associated cardiotoxicity in cancer patients.

INTRODUCTION: Anthracycline chemotherapeutic agents are widely used in the treatment of hematological and solid tumors, working principally through DNA intercalation and topoisomerase II inhibition. However, they are also well known to have cardiotoxic sequelae, commonly denoted as a reduction in ejection fraction. Drug-associated cardiotoxicity remains a significant limiting factor in the use of anthracyclines. AREAS COVERED: In this review, we explore the potential mechanisms of anthracycline-associated cardiotoxicity, identifying high-risk cohorts and approaches to cardiovascular monitoring. The mechanisms through which cardiotoxicity occurs are complex and diverse, ultimately leading to increased oxidative stress, mitochondrial dysfunction, and subsequent cellular apoptosis. Many of the cardiotoxic effects of anthracyclines exhibit a dose-dependent cumulative relationship and are more apparent in patients with previously existing cardiovascular risk factors. Long-term cardiovascular monitoring and optimization of risk factors, prior to commencing treatment as well as beyond the time of treatment, is therefore essential. EXPERT OPINION: We discuss some of the pharmacological strategies proposed to mitigate anthracycline-associated cardiotoxicity as well as prevention strategies to reduce the burden of coexisting cardiovascular risk factors. We highlight methods of early detection of patient cohorts who are at increased risk of developing anthracycline-associated cardiotoxicity and identify potential avenues for further research

Gyrospun antimicrobial nanoparticle loaded fibrous polymeric filters

A one step approach to prepare hybrid nanoparticle embedded polymer fibres using pressurised gyration is presented. Two types of novel antimicrobial nanoparticles and poly(methylmethacrylate) polymer were used in this work. X-ray diffraction analysis of the nanoparticles revealed Ag, Cu and W are the main elements present in them. The concentration of the polymer solution and the nanoparticle concentration had a significant influence on the fibre diameter, pore size and morphology. Fibres with a diameter in the range of 6-20. μm were spun using 20. wt% polymer solutions containing 0.1, 0.25 and 0.5 wt% nanoparticles under 0.3. MPa working pressure and a rotational speed of 36,000. rpm. Continuous, bead-free fibre morphologies were obtained for each case. The pore size in the fibres varied between 36 and 300. nm. Successful incorporation of the nanoparticles in polymer fibres was confirmed by energy dispersive x-ray analysis. The fibres were also gyrospun on to metallic discs to prepare filters which were tested for their antibacterial activity on a suspension of Pseudomonas aeruginosa. Nanoparticle loaded fibres showed higher antibacterial efficacy than pure poly(methylmethacrylate) fibres

Deep Annotation of Populus trichocarpa microRNAs from Diverse Tissue Sets

Populus trichocarpa is an important woody model organism whose entire genome has been sequenced. This resource has facilitated the annotation of microRNAs (miRNAs), which are short non-coding RNAs with critical regulatory functions. However, despite their developmental importance, P. trichocarpa miRNAs have yet to be annotated from numerous important tissues. Here we significantly expand the breadth of tissue sampling and sequencing depth for miRNA annotation in P. trichocarpa using high-throughput smallRNA (sRNA) sequencing. miRNA annotation was performed using three individual next-generation sRNA sequencing runs from separate leaves, xylem, and mechanically treated xylem, as well as a fourth run using a pooled sample containing vegetative apices, male flowers, female flowers, female apical buds, and male apical and lateral buds. A total of 276 miRNAs were identified from these datasets, including 155 previously unannotated miRNAs, most of which are P. trichocarpa specific. Importantly, we identified several xylem-enriched miRNAs predicted to target genes known to be important in secondary growth, including the critical reaction wood enzyme xyloglucan endo-transglycosylase/hydrolase and vascular-related transcription factors. This study provides a thorough genome-wide annotation of miRNAs in P. trichocarpa through deep sRNA sequencing from diverse tissue sets. Our data significantly expands the P. trichocarpa miRNA repertoire, which will facilitate a broad range of research in this major model system

Porcine FcγRIIb Mediates Enhancement of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection

Antibody-dependent enhancement (ADE) of virus infection caused by the uptake of virus-antibody complexes by FcγRs is a significant obstacle to the development of effective vaccines to control certain human and animal viral diseases. The activation FcγRs, including FcγRI and FcγRIIa have been shown to mediate ADE infection of virus. In the present paper, we showed that pocine FcγRIIb, an inhibitory FcγR, mediates ADE of PRRSV infection. Stable Marc-145 cell lines expressing poFcγRIIb (Marc-poFcγRII) were established. The relative yield of progeny virus was significantly increased in the presence of sub-neutralization anti-PRRSV antibody. The Fab fragment and normal porcine sera had no effect. Anti-poFcγRII antibody inhibited the enhancement of infection when cells were infected in the presence of anti-PRRSV antibody, but not when cells were infected in the absence of antibody. These results indicate that enhancement of infection in these cells by anti-PRRSV virus antibody is FcγRII-mediated. Identification of the inhibitory FcγR mediating ADE infection should expand our understanding of the mechanisms of pathogenesis for a broad range of infectious diseases and may open many approaches for improvements to the treatment and prevention of such diseases

Targeting HSP90 for cancer therapy

Heat-shock proteins (HSPs) are molecular chaperones that regulate protein folding to ensure correct conformation and translocation and to avoid protein aggregation. Heat-shock proteins are increased in many solid tumours and haematological malignancies. Many oncogenic proteins responsible for the transformation of cells to cancerous forms are client proteins of HSP90. Targeting HSP90 with chemical inhibitors would degrade these oncogenic proteins, and thus serve as useful anticancer agents. This review provides an overview of the HSP chaperone machinery and the structure and function of HSP90. We also highlight the key oncogenic proteins that are regulated by HSP90 and describe how inhibition of HSP90 could alter the activity of multiple signalling proteins, receptors and transcriptional factors implicated in carcinogenesis

The Hexameric Structures of Human Heat Shock Protein 90

The human 90-kDa heat shock protein (HSP90) functions as a dimeric molecular chaperone. HSP90 identified on the cell surface has been found to play a crucial role in cancer invasion and metastasis, and has become a validated anti-cancer target for drug development. It has been shown to self-assemble into oligomers upon heat shock or divalent cations treatment, but the functional role of the oligomeric states in the chaperone cycle is not fully understood.Here we report the crystal structure of a truncated HSP90 that contains the middle segment and the carboxy-terminal domain, termed MC-HSP90. The structure reveals an architecture with triangular bipyramid geometry, in which the building block of the hexameric assembly is a dimer. In solution, MC-HSP90 exists in three major oligomer states, namely dimer, tetramer and hexamer, which were elucidated by size exclusion chromatography and analytical ultracentrifugation. The newly discovered HSP90 isoform HSP90N that lacks the N-terminal ATPase domain also exhibited similar oligomerization states as did MC-HSP90.While lacking the ATPase domain, both MC-HSP90 and HSP90N can self-assemble into a hexameric structure, spontaneously. The crystal structure of MC-HSP90 reveals that, in addition to the C-terminal dimerization domain, the residue W320 in the M domain plays a critical role in its oligomerization. This study not only demonstrates how the human MC-HSP90 forms a hexamer, but also justifies the similar formation of HSP90N by using 3D modeling analysis

Anti-Cancer Effect of HIV-1 Viral Protein R on Doxorubicin Resistant Neuroblastoma

Several unique biological features of HIV-1 Vpr make it a potentially powerful agent for anti-cancer therapy. First, Vpr inhibits cell proliferation by induction of cell cycle G2 arrest. Second, it induces apoptosis through multiple mechanisms, which could be significant as it may be able to overcome apoptotic resistance exhibited by many cancerous cells, and, finally, Vpr selectively kills fast growing cells in a p53-independent manner. To demonstrate the potential utility of Vpr as an anti-cancer agent, we carried out proof-of-concept studies in vitro and in vivo. Results of our preliminary studies demonstrated that Vpr induces cell cycle G2 arrest and apoptosis in a variety of cancer types. Moreover, the same Vpr effects could also be detected in some cancer cells that are resistant to anti-cancer drugs such as doxorubicin (DOX). To further illustrate the potential value of Vpr in tumor growth inhibition, we adopted a DOX-resistant neuroblastoma model by injecting SK-N-SH cells into C57BL/6N and C57BL/6J-scid/scid mice. We hypothesized that Vpr is able to block cell proliferation and induce apoptosis regardless of the drug resistance status of the tumors. Indeed, production of Vpr via adenoviral delivery to neuroblastoma cells caused G2 arrest and apoptosis in both drug naïve and DOX-resistant cells. In addition, pre-infection or intratumoral injection of vpr-expressing adenoviral particles into neuroblastoma tumors in SCID mice markedly inhibited tumor growth. Therefore, Vpr could possibly be used as a supplemental viral therapeutic agent for selective inhibition of tumor growth in anti-cancer therapy especially when other therapies stop working

Mucin Biopolymers As Broad-Spectrum Antiviral Agents

Mucus is a porous biopolymer matrix that coats all wet epithelia in the human body and serves as the first line of defense against many pathogenic bacteria and viruses. However, under certain conditions viruses are able to penetrate this infection barrier, which compromises the protective function of native mucus. Here, we find that isolated porcine gastric mucin polymers, key structural components of native mucus, can protect an underlying cell layer from infection by small viruses such as human papillomavirus (HPV), Merkel cell polyomavirus (MCV), or a strain of influenza A virus. Single particle analysis of virus mobility inside the mucin barrier reveals that this shielding effect is in part based on a retardation of virus diffusion inside the biopolymer matrix. Our findings suggest that purified mucins may be used as a broad-range antiviral supplement to personal hygiene products, baby formula or lubricants to support our immune system.National Institutes of Health (U.S.) (grant P30-ES002109)National Institutes of Health (U.S.) (grant P50-GM068763)German Academic Exchange Service (Postdoctoral fellowship