A multi-targeting bionanomatrix coating to reduce capsular contracture development on silicone implants.

Background: Capsular contracture is a critical complication of silicone implantation caused by fibrotic tissue formation from excessive foreign body responses. Various approaches have been applied, but targeting the mechanisms of capsule formation has not been completely solved. Myofibroblast differentiation through the transforming growth factor beta (TGF-β)/p-SMADs signaling is one of the key factors for capsular contracture development.

MiR-146a encapsulated liposomes reduce vascular inflammatory responses through decrease of ICAM-1 expression, macrophage activation, and foam cell formation.

Vascular insults can create an inflammatory cascade involving endothelial cell, smooth muscle cell, and macrophage activation which can eventually lead to vascular disease such as atherosclerosis. Several studies have identified microRNA 146a's (miR-146a) anti-inflammatory potential based on its role in regulating the nuclear factor kappa beta (NF-κβ) pathway. Therefore, in this study, we introduced exogenous miR-146a encapsulated by liposomes to lipopolysaccharide (LPS) stimulated vascular cells and macrophages to reduce inflammatory responses.

Subcutaneous Administration of a Nitric Oxide-Releasing Nanomatrix Gel Ameliorates Obesity and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

Nitric oxide (NO) is a gaseous signaling molecule, which plays crucial roles in various biological processes, including inflammatory responses, metabolism, cardiovascular functions, and cognitive function. NO bioavailability is reduced with aging and cardiometabolic disorders in humans and rodents. NO stimulates the metabolic rate by increasing the mitochondrial biogenesis and brown fat activation.

Endothelium-Mimicking Nanomatrix Coating to Enhance Endothelialization after Left Atrial Appendage Closure Device Implantation.

Blood clots (90%) originate from the left atrial appendage (LAA) in non-valvular atrial fibrillation patients and are a major cause of embolic stroke. Long-term anticoagulation therapy has been used to prevent thrombus formation, but its use is limited in patients at a high risk for bleeding complications. Thus, left atrial appendage closure (LAAC) devices for LAA occlusion are well-established as an alternative to the anticoagulation therapy.

Nitric oxide releasing nanomatrix gel treatment inhibits venous intimal hyperplasia and improves vascular remodeling in a rodent arteriovenous fistula.

Vascular access is the lifeline for hemodialysis patients and the single most important component of the hemodialysis procedure. Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis patients, but nearly 60% of AVFs created fail to successfully mature due to early intimal hyperplasia development and poor outward remodeling. There are currently no therapies available to prevent AVF maturation failure.

Recent advances in nanomaterials for therapy and diagnosis for atherosclerosis.

Atherosclerosis is a chronic inflammatory disease driven by lipid accumulation in arteries, leading to narrowing and thrombosis. It affects the heart, brain, and peripheral vessels and is the leading cause of mortality in the United States. Researchers have strived to design nanomaterials of various functions, ranging from non-invasive imaging contrast agents, targeted therapeutic delivery systems to multifunctional nanoagents able to target, diagnose, and treat atherosclerosis.

Influence of physiochemical properties on the subcutaneous absorption and bioavailability of monoclonal antibodies.

Many therapeutic monoclonal antibodies (mAbs) were initially developed for intravenous (IV) administration. As a means to improve mAb drug-ability and the patient experience, subcutaneous (SC) administration is an increasingly important delivery route for mAbs. Unlike IV administration, bioavailability limitations for antibodies have been reported following SC injection and can dictate whether a mAb is administered via this parenteral route.

Evaluation of Viscoelastic Properties, Blood Coagulation, and Cellular Responses of a Temperature-Sensitive Gel for Hemostatic Application.

Hemorrhagic blood loss from traumatic injury is the leading cause of death in severe accidents and combat injuries. Treating and stopping blood loss in a timely and effective manner is essential for the survival of the patient. Currently, QuikClot and dry fibrin sealant dressing are well-known approaches for hemostatic treatment.

High density lipoprotein mimicking nanoparticles for atherosclerosis.

Atherosclerosis is a major contributor to many cardiovascular events, including myocardial infarction, ischemic stroke, and peripheral arterial disease, making it the leading cause of death worldwide. High-density lipoproteins (HDL), also known as "good cholesterol", have been shown to demonstrate anti-atherosclerotic efficacy through the removal of cholesterol from foam cells in atherosclerotic plaques. Because of the excellent anti-atherosclerotic properties of HDL, in the past several years, there has been tremendous attention in designing HDL mimicking nanoparticles (NPs) of varying functions to image, target, and treat atherosclerosis.

Absence of glucagon and insulin action reveals a role for the GLP-1 receptor in endogenous glucose production.

The absence of insulin results in oscillating hyperglycemia and ketoacidosis in type 1 diabetes. Remarkably, mice genetically deficient in the glucagon receptor (Gcgr) are refractory to the pathophysiological symptoms of insulin deficiency, and therefore, studies interrogating this unique model may uncover metabolic regulatory mechanisms that are independent of insulin. A significant feature of Gcgr-null mice is the high circulating concentrations of GLP-1.

Is imaging the extremities with PEM feasible? A novel application for a high-resolution positron emission scanner.

Introduction: Positron emission mammography (PEM) has better spatial resolution than positron emission tomography/computed tomography (PET/CT), or PET/CT. We evaluated the feasibility of extremity imaging with PEM using PET as a standard.

Methods/materials: Fourteen patients underwent sequential PET/CT and PEM.

Correlation of PUV and SUV in the extremities while using PEM as a high-resolution positron emission scanner.

Objective: Owing to its unique configuration of two adjustable plate detectors positron emission mammography, or PEM, could theoretically also function as a high-resolution positron emission scanner for the extremities or neck. PEM quantitates its activity via a "PEM uptake value," or PUV, and although its relationship to the standardized uptake value, or SUV, has been demonstrated in the breasts, to our knowledge there are no studies validating PUV in other sites such as the extremities.

Materials And Methods: This was a retrospective chart review of two separate protocols of a total of 15 patients.

Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein.

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists are novel agents for type 2 diabetes treatment, offering glucose-dependent insulinotropic effects, reduced glucagonemia and a neutral bodyweight or weight-reducing profile. However, a short half-life (minutes), secondary to rapid inactivation by dipeptidyl peptidase-IV (DPP-IV) and excretion, limits the therapeutic potential of the native GLP-1 hormone. Recently, the GLP-1 receptor agonist exenatide injected subcutaneously twice daily established a novel therapy class.

A global benchmark study using affinity-based biosensors.

To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times.

Purification and characterization of secreted human leptin produced in baculovirus-infected insect cells.

The product of the human ob (obesity) gene, leptin, appears to function in the maintenance of body weight in vivo. When injected into mice, this hormone reduces food consumption and causes weight loss. This work has been done with recombinant leptin (re-leptin) purified and renatured from inclusion bodies in Escherichia coli.

Equilibrium intermediates in the denaturation of human insulin and two monomeric insulin analogs.

The equilibrium denaturation of human insulin in a monomer-inducing solvent and of two monomeric insulin analogs, lysB28proB29 insulin and aspB10desB28-30 insulin, was reexamined [Brems, D. N., Brown, P.

Improved insulin stability through amino acid substitution.

Insulin analogs designed to decrease self-association and increase absorption rates from subcutaneous tissue were found to have altered stability. Replacement of HB10 with aspartic acid increased stability while substitutions at B28 and/or B29 were either comparable to insulin or had decreased stability. The principal chemical degradation product of accelerated storage conditions was a disulfide-linked multimer that was formed through a disulfide interchange reaction which resulted from beta-elimination of the disulfides.

Controlling heat stress - administrative versus physical control.

The collective effectiveness of several heat stress prevention measures has been evaluated. The relative merits of both physical and administrative controls and their interrelationships have been explored. It is concluded that a combination of physical and administrative control is more effective than any single physical or administrative control in managing heat stress.