A Ligand Peptide Motif Selected from a Cancer Patient Is a Receptor-Interacting Site within Human Interleukin-11

Interleukin-11 (IL-11) is a pleiotropic cytokine approved by the FDA against chemotherapy-induced thrombocytopenia. From a combinatorial selection in a cancer patient, we isolated an IL-11-like peptide mapping to domain I of the IL-11 (sequence CGRRAGGSC). Although this motif has ligand attributes, it is not within the previously characterized interacting sites. Here we design and validate in-tandem binding assays, site-directed mutagenesis and NMR spectroscopy to show (i) the peptide mimics a receptor-binding site within IL-11, (ii) the binding of CGRRAGGSC to the IL-11Rα is functionally relevant, (iii) Arg4 and Ser8 are the key residues mediating the interaction, and (iv) the IL-11-like motif induces cell proliferation through STAT3 activation. These structural and functional results uncover an as yet unrecognized receptor-binding site in human IL-11. Given that IL-11Rα has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs

Method for isolation and identification of potato virus M, S, X, Y

The common procedure for isolation of potato virus M, S, X, Y, based on precipitation with PEG (final concentration of 6%) and purification by gel filtration on the Sepharose 2B is decribed. Identification of individual viruses is performed on the basis of electrophoretic analysis of viral coat protein, extracted from purified virus fraction. In electrophoresis coat proteins give single bands with the relative mobility of 1.0, 0.97, 0.94, and 0.80 for PVY, PVS, PVM and PVX respectively. Determination of protein or RNA content in virus fraction after chromatography allows the quantitative estimation of virus in plant material

Tannic acid-modified silver nanoparticles for wound healing: the importance of size

Piotr Orlowski,1 Magdalena Zmigrodzka,2 Emilia Tomaszewska,3 Katarzyna Ranoszek-Soliwoda,3 Monika Czupryn,1 Malgorzata Antos-Bielska,1 Janusz Szemraj,4 Grzegorz Celichowski,3 Jaroslaw Grobelny,3 Malgorzata Krzyzowska1 1Military Institute of Hygiene and Epidemiology, Warsaw, Poland; 2Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences (WULS-SGGW), Warsaw, Poland; 3Department of Materials Technology and Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland; 4Bionanopark, Lodz, Poland Introduction: Silver nanoparticles (AgNPs) have been shown to promote wound healing and to exhibit antimicrobial properties against a broad range of bacteria. In our previous study, we prepared tannic acid (TA)-modified AgNPs showing a good toxicological profile and immunomodulatory properties useful for potential dermal applications.Methods: In this study, in vitro scratch assay, antimicrobial tests, modified lymph node assay as well as a mouse splint wound model were used to access the wound healing potential of TA-modified and unmodified AgNPs.Results: TA-modified but not unmodified AgNPs exhibited effective antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli and stimulated migration of keratinocytes in vitro. The tests using the mouse splint wound model showed that TA-modified 33 and 46 nm AgNPs promoted better wound closure, epithelialization, angiogenesis and formation of the granulation tissue. Additionally, AgNPs elicited expression of VEGF-α, PDGF-β and TGF-β1 cytokines involved in wound healing more efficiently in comparison to control and TA-treated wounds. However, both the lymph node assay and the wound model showed that TA-modified AgNPs sized 13 nm can elicit strong inflammatory response not only during wound healing but also when applied to the damaged skin.Conclusion: TA-modified AgNPs sized >26 nm promote wound healing better than TA-modified or unmodified AgNPs. These findings suggest that TA-modified AgNPs sized >26 nm may have a promising application in wound management. Keywords: hydrolyzable tannin, split wound, silver, antimicrobials, inflammation, fibroblasts, monocyte

Electronic patient-reported outcomes in clinical kidney practice (ePRO Kidney): a process evaluation of educational support for clinicians

Background: Patient-reported outcomes (PROs) are increasingly mandated in kidney care to incorporate patients’ perspectives. Objectives: We assessed whether educational support for clinicians using electronic (e)PROs could enhance person-centered care. Design: A process evaluation, using a mixed methods longitudinal comparative concurrent design was undertaken of educational support to clinicians on routine use of ePROs. In two urban home dialysis clinics in Alberta, Canada, patients completed ePROs. At the implementation site, clinicians were provided with ePROs and clinician-oriented education via voluntary workshops. At the non-implementation site, neither were provided. Person-centered care was measured using the Patient Assessment of Chronic Illness Care-20 (PACIC-20). Methods: Longitudinal structural equation models (SEMs) compared change in overall PACIC scores. The interpretive description approach, using thematic analysis of qualitative data, further evaluated processes of implementation. Results: Data were collected from questionnaires completed by 543 patients, 4 workshops, 15 focus groups, and 37 interviews. There was no overall difference in person-centered care throughout the study, including after delivery of workshops. The longitudinal SEMs revealed substantial individual-level variability in overall PACIC trajectories. However, there was no improvement at the implementation site and no difference between the sites during both the pre- and post-workshop periods. Similar results were obtained for each PACIC domain. Qualitative analysis provided insights into why there was no substantial difference between sites: (1) clinicians wanted to see kidney symptoms, not quality of life, (2) workshops were tailored to clinicians’ educational needs, not patients’ needs, and (3) variable use of ePRO data by clinicians. Conclusion: Training clinicians on use of ePROs is complex and likely only part of what is required to enhance person-centered care. Registration: NCT03149328. https://clinicaltrials.gov/ct2/show/NCT0314932