Antibacterial Efficacy of a Chitosan-Based Hydrogel Modified With Epsilon-Poly-l-Lysine Against Pseudomonas aeruginosa in a Murine-Infected Burn Wound Model.

Introduction: Because antibiotic resistance is increasing worldwide and the leading cause of death in burn patients is an infection, an urgent need exists for nonantibiotic approaches to eliminate multidrug-resistant bacteria from burns to prevent their systemic dissemination and sepsis. We previously demonstrated the significant antibiofilm activity of a chitosan (CS) hydrogel containing the antimicrobial peptide epsilon-poly-l-lysine (EPL) against multidrug-resistant Pseudomonas aeruginosa using ex vivo porcine skin. In this study, we evaluated the in vivo antibacterial efficacy of a CS/EPL hydrogel against P.

Priming With Toll-Like Receptor 3 Agonist Poly(I:C) Enhances Content of Innate Immune Defense Proteins but Not MicroRNAs in Human Mesenchymal Stem Cell-Derived Extracellular Vesicles.

Mesenchymal stem cells (MSCs) help fight infection by promoting direct bacterial killing or indirectly by modulating the acute phase response, thereby decreasing tissue injury. Recent evidence suggests that extracellular vesicles (EVs) released from MSCs retain antimicrobial characteristics that may be enhanced by pretreatment of parent MSCs with the toll-like receptor 3 (TLR3) agonist poly(I:C). Our aim was to determine whether poly(I:C) priming can modify EV content of miRNAs and/or proteins to gain insight into the molecular mechanisms of their enhanced antimicrobial function.

Antibiofilm activity of chitosan/epsilon-poly-L-lysine hydrogels in a porcine ex vivo skin wound polymicrobial biofilm model.

As antibiotic resistance continues to increase globally, there is an urgency for novel, non-antibiotic approaches to control chronic drug-resistant infections, particularly those associated with polymicrobial biofilm formation in chronic wounds. Also needed are clinically relevant polymicrobial biofilm models that can be utilized to assess the efficacy of innovative therapeutics against mature biofilms. We successfully developed a highly reproducible porcine ex vivo skin wound polymicrobial biofilm model using clinical isolates of multidrug-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Candida albicans.

Inhibition of microRNA-124-3p as a novel therapeutic strategy for the treatment of Gulf War Illness: Evaluation in a rat model.

Gulf War Illness (GWI) is a chronic, multisymptom illness that continues to affect up to 30% of veterans deployed to the Persian Gulf during the 1990-1991 Gulf War. After nearly 30 years, useful treatments for GWI are lacking and underlying cellular and molecular mechanisms involved in its pathobiology remain poorly understood, although exposures to pyridostigmine bromide (PB) and pesticides are consistently identified to be among the strongest risk factors. Alleviation of the broad range of symptoms manifested in GWI, which involve the central nervous system, the neuroendocrine system, and the immune system likely requires therapies that are able to activate and inactivate a large set of orchestrated genes.

Evaluation of a Novel Hybrid Viable Bioprosthetic Mesh in a Model of Mesh Infection.

Background: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of material used. Our laboratory previously showed that augmenting acellular bioprosthetic mesh with allogeneic mesenchymal stem cells (MSC) enhances resistance to bacterial colonization in vivo and preserves mesh integrity. This study's aim was to determine whether augmentation of non-crosslinked porcine dermis (Strattice) with commercially available, cryopreserved, viable MSC-containing human placental tissue (Stravix) similarly improves infection resistance after inoculation with () using an established mesh infection model.

Bone Marrow-Derived Mesenchymal Stem Cells Enhance Bacterial Clearance and Preserve Bioprosthetic Integrity in a Model of Mesh Infection.

Background: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of the material used. Recently, mesenchymal stem cells (MSCs) have been shown to possess favorable immunomodulatory properties and improve tissue incorporation when seeded onto bioprosthetics. The aim of this study was to evaluate whether seeding noncrosslinked bovine pericardium (Veritas Collagen Matrix) with allogeneic bone marrow-derived MSCs improves infection resistance in vivo after inoculation with Escherichia coli (E.

Long-term epigenetic alterations in a rat model of Gulf War Illness.

Gulf War Illness (GWI) is a chronic, multisymptom illness that affects 25% of the 700,000 US veterans deployed to the Persian Gulf during the 1990-1991 Gulf War. Central nervous system impairments are among the most common symptoms reported, including memory dysfunction and depression. After 25 years, the diagnosis remains elusive, useful treatments are lacking, and the cause is poorly understood, although exposures to pyridostigmine bromide (PB) and pesticides are consistently identified to be among the strongest risk factors.

Investigation of a novel molecular descriptor for the lead optimization of 4-aminoquinazolines as vascular endothelial growth factor receptor-2 inhibitors: application for quantitative structure-activity relationship analysis in lead optimization.

We investigated the use of infrared vibrational frequency of ligands as a potential novel molecular descriptor in three different molecular target and chemical series. The vibrational energy of a ligand was approximated from the sum of infrared (IR) absorptions of each functional group within a molecule and normalized by its molecular weight (MDIR). Calculations were performed on a set of 4-aminoquinazolines with similar docking scores for the VEGFR2/KDR receptor.

Generation and characterization of mouse monoclonal antibodies against CIP75, an UbL-UBA domain-containing protein.

CIP75 is a member of the UbL(ubiquitin-like)-UBA (ubiquitin-associated) domain containing protein family, which has a variety of functions. One specific role described for several members of the UbL-UBA family is the involvement in the proteasomal degradation of target proteins. We have reported that CIP75 interacts with the gap junction protein, connexin43 (Cx43), and that CIP75 may modulate the proteasomal degradation of Cx43.

A novel connexin43-interacting protein, CIP75, which belongs to the UbL-UBA protein family, regulates the turnover of connexin43.

The degradation of connexin43 (Cx43) has been reported to involve both lysosomal and proteasomal degradation pathways; however, very little is known about the mechanisms regulating these Cx43 degradation pathways. Using yeast two-hybrid, glutathione S-transferase pull-down, and co-immunoprecipitation approaches, we have identified a novel Cx43-interacting protein of approximately 75 kDa, CIP75. Laser confocal microscopy showed that CIP75 is located primarily at the endoplasmic reticulum, as indicated by the calnexin marker, with Cx43 co-localization in this perinuclear region.

Connexin43 PDZ2 binding domain mutants create functional gap junctions and exhibit altered phosphorylation.

Connexin43 (Cx43) is the most abundantly expressed gap junction protein. The C-terminal tail of Cx43 is important for regulation of gap junctions via phosphorylation of specific tyrosine and serine residues and through interactions with cellular proteins. The C-terminus of Cx43 has been shown to interact with the PDZ2 domain of the tight and adherens junction associated zona occludens 1 (ZO-1) protein.

Novel rab GAP-like protein, CIP85, interacts with connexin43 and induces its degradation.

Gap junctions play critical roles in tissue function and homeostasis. Connexin43 (Cx43) is a major gap junction protein expressed in the mammalian heart and other tissues and may be regulated by its interaction with other cellular proteins. Using the yeast two-hybrid screen, we identified a novel Cx43-interacting protein of 85-kDa, CIP85, which contains a single TBC, SH3, and RUN domain, in addition to a short coiled coil region.