Assessment of an scFv Antibody Fragment Against ELTD1 in a G55 Glioblastoma Xenograft Model.

Glioblastoma (GBM), the most common primary brain tumor found in adults, is extremely aggressive. These high-grade gliomas, which are very diffuse, highly vascular, and invasive, undergo unregulated vascular angiogenesis. Despite available treatments, the median survival for patients is dismal.

Molecular changes associated with spinal cord aging.

Age-related muscle weakness and loss of muscle mass (sarcopenia) is a universal problem in the elderly. Our previous studies indicate that alpha motor neurons (α-MNs) play a critical role in this process. The goal of the current study is to uncover changes in the aging spinal cord that contribute to loss of innervation and the downstream degenerative processes that occur in skeletal muscle.

Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model.

Glioblastoma is an aggressive brain tumour found in adults, and the therapeutic approaches available have not significantly increased patient survival. Recently, we discovered that ELTD1, an angiogenic biomarker, is highly expressed in human gliomas. Polyclonal anti-ELTD1 treatments were effective in glioma pre-clinical models, however, pAb binding is potentially promiscuous.

PEGylated reduced-graphene oxide hybridized with FeO nanoparticles for cancer photothermal-immunotherapy.

Photoimmunotherapy has attracted much attention recently for the treatment of metastatic tumors. The development of smart nanocomposites for imaging-guided therapies is needed to improve the efficacy of cancer treatment. Herein, a PEGylated nanocomposite was developed for photothermal-immunotherapy.

Analysis of retention of gadolinium by brain, bone, and blood following linear gadolinium-based contrast agent administration in rats with experimental sepsis.

Purpose: It is important to identify populations that may be vulnerable to the brain deposition of gadolinium (Gd) from MRI contrast agents. At intervals from 24 hours to 6 weeks following injection of a linear Gd contrast agent, the brain, blood and bone content of Gd were compared between control rats and those with experimental endotoxin-induced sepsis that results in neuroinflammation and blood-brain barrier disruption.

Methods: Male rats were injected intraperitoneally with 10 mg/kg lipopolysaccharide.

Epstein Barr virus nuclear antigen 1 (EBNA-1) peptides recognized by adult multiple sclerosis patient sera induce neurologic symptoms in a murine model.

Multiple sclerosis (MS) is an autoimmune demyelinating disease with progressive neurodegeneration and complex etiology likely involving genetic and environmental factors. MS has been associated with Epstein Barr virus (EBV) infection, with patients often showing enhanced responses to EBV antigens. To determine whether abnormal EBV nuclear antigen-1 (EBNA-1) humoral immunity can serve as an initiator of autoimmune responses in MS, we investigated the fine specificities of the humoral immune response against EBNA-1 in MS patients using solid phase epitope mapping.

Anti-inflammatory agent, OKN-007, reverses long-term neuroinflammatory responses in a rat encephalopathy model as assessed by multi-parametric MRI: implications for aging-associated neuroinflammation.

Lipopolysaccharide (LPS)-induced encephalopathy induces neuroinflammation. Long-term neuroinflammation is associated with aging and subsequent cognitive impairment (CI). We treated rats that had LPS-induced neuroinflammation with OKN-007, with an anti-inflammatory agent currently considered an anti-cancer investigational new drug in clinical trials for glioblastoma (GBM).

Lipopolysaccharide exposure in a rat sepsis model results in hippocampal amyloid-β plaque and phosphorylated tau deposition and corresponding behavioral deficits.

Sepsis is a severe systemic inflammatory response to infection associated with acute and chronic neurocognitive consequences, including an increased risk of later-life dementia. In a lipopolysaccharide-induced rat sepsis model, we have demonstrated neuroinflammation, cortical amyloid-beta plaque deposition, and increased whole brain levels of phosphorylated tau. Hippocampal abnormalities, particularly those of the dentate gyrus, are seen in Alzheimer's disease and age-related memory loss.

Using MRI to measure in vivo free radical production and perfusion dynamics in a mouse model of elevated oxidative stress and neurogenic atrophy.

Mitochondrial dysfunction, reactive oxygen species (ROS) and oxidative damage have been implicated to play a causative role in age-related skeletal muscle atrophy and weakness (i.e. sarcopenia).

An investigation of the glycosaminoglycan contribution to biaxial mechanical behaviours of porcine atrioventricular heart valve leaflets.

The atrioventricular heart valve (AHV) leaflets have a complex microstructure composed of four distinct layers: atrialis, ventricularis, fibrosa and spongiosa. Specifically, the spongiosa layer is primarily proteoglycans and glycosaminoglycans (GAGs). Quantification of the GAGs' mechanical contribution to the overall leaflet function has been of recent focus for aortic valve leaflets, but this characterization has not been reported for the AHV leaflets.

An investigation of layer-specific tissue biomechanics of porcine atrioventricular valve anterior leaflets.

Atrioventricular heart valves (AHVs) are composed of structurally complex and morphologically heterogeneous leaflets. The coaptation of these leaflets during the cardiac cycle facilitates unidirectional blood flow. Valve regurgitation is treated preferably by surgical repair if possible or replacement based on the disease state of the valve tissue.

Regional biaxial mechanical data of the mitral and tricuspid valve anterior leaflets.

The collective data associated with this article presents the biaxial mechanical behavior for six smaller, delimited regions of the mitral valve and tricuspid valve anterior leaflets. Each data set consists of five columns of data, specifically: (i) biaxial testing protocol ID, (ii) circumferential stretch, (iii) radial stretch, (iv) circumferential membrane tension, and (v) radial membrane tension. For further elaboration regarding methodologies or results of the biaxial mechanical characterization please refer to the companion article Laurence, 2019.

Targeting ELTD1, an angiogenesis marker for glioblastoma (GBM), also affects VEGFR2: molecular-targeted MRI assessment.

Glioblastomas (GBM) are deadly brain tumors that currently do not have long-term patient treatments available. GBM overexpress the angiogenesis factor VEGF and its receptor VEGFR2. ETLD1 (epidermal growth factor, latrophilin and seven transmembrane domain-containing protein 1), a G-protein coupled receptor (GPCR) protein, we discovered as a biomarker for high-grade gliomas, is also a novel regulator of angiogenesis.

Immunomodulatory response of layered small intestinal submucosa in a rat bladder regeneration model.

Based on the hypothesis that bioscaffold permeability is a major factor in determining the outcome of histologically complete and functional bladder regeneration, we evaluated regeneration processes of four-layer porcine small intestinal submucosa (SIS) construct; and compared results between rat bladders augmented with single-layer SIS bioscaffolds. Sprague-Dawley female rats were subjected to hemi-cystectomy followed by anastomosis of a patch of either single- or four-layer porcine SIS. Permeability was analyzed in situ using magnetic resonance imaging (MRI) at post-operative days 7 and 14.

An investigation of regional variations in the biaxial mechanical properties and stress relaxation behaviors of porcine atrioventricular heart valve leaflets.

The facilitation of proper blood flow through the heart depends on proper function of heart valve components, and alterations to any component can lead to heart disease or failure. Comprehension of these valvular diseases is reliant on thorough characterization of healthy heart valve structures for use in computational models. Previously, computational models have treated these leaflet structures as a structurally and mechanically homogenous material, which may not be an accurate description of leaflet mechanical response.

OKN-007 Increases temozolomide (TMZ) Sensitivity and Suppresses TMZ-Resistant Glioblastoma (GBM) Tumor Growth.

Treatment of glioblastoma (GBM) remains a challenge using conventional chemotherapy, such as temozolomide (TMZ), and is often ineffective as a result of drug resistance. We have assessed a novel nitrone-based agent, OKN-007, and found it to be effective in decreasing tumor volumes and increasing survival in orthotopic GBM xenografts by decreasing cell proliferation and angiogenesis and increasing apoptosis. In this study, we assessed combining OKN-007 with TMZ in vivo in a human G55 GBM orthotopic xenograft model and in vitro in TMZ-resistant and TMZ-sensitive human GBM cell lines.

Biaxial mechanical data of porcine atrioventricular valve leaflets.

This dataset contains the anisotropic tissue responses of porcine atrioventricular valve leaflets to force-controlled biaxial mechanical testing. The set includes the first Piola-Kirchhoff Stress and the specimen stretches (λ) in both circumferential and radial tissue directions (C and R, respectively) for the mitral valve anterior and posterior leaflets (MVAL and MVPL), and the tricuspid valve anterior, posterior, and septal leaflets (TVAL, TVPL, and TVSL) from six porcine hearts at five separate force-controlled biaxial loading protocols. This dataset is associated with a companion journal article, which can be consulted for further information about the methodology, results, and discussion of this biaxial mechanical testing (Jett et al.

An investigation of the anisotropic mechanical properties and anatomical structure of porcine atrioventricular heart valves.

Valvular heart diseases are complex disorders, varying in pathophysiological mechanism and affected valve components. Understanding the effects of these diseases on valve functionality requires a thorough characterization of the mechanics and structure of the healthy heart valves. In this study, we performed biaxial mechanical experiments with extensive testing protocols to examine the mechanical behaviors of the mitral valve and tricuspid valve leaflets.

Exosomes as Theranostics for Lung Cancer.

Extensive research in genetics and genomics has revealed that lung cancer is a physiologically complex and genetically heterogeneous disease. Although molecular targets that can yield favorable response have been identified, those targets cannot be exploited due to the lack of suitable drug carriers. Furthermore, lung cancer often is diagnosed at an advanced stage when the disease has metastasized.

Lipopolysaccharide endotoxemia induces amyloid-β and p-tau formation in the rat brain.

Amyloid beta (Aβ) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aβ may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise.

Preclinical Animal Studies of Intravesical Recombinant Human Proteoglycan 4 as a Novel Potential Therapy for Diseases Resulting From Increased Bladder Permeability.

Objective: To test in an animal model the hypothesis that recombinant human proteoglycan 4 (rhPRG4; lubricin), a highly O-glycosylated mucin-like glycoprotein, may be a novel surface-active therapeutic for treating bladder permeability with comorbid bowel permeability. Previously we showed that inducing bladder permeability in rats with dilute protamine sulfate (PS) produced colonic permeability and visceral hypersensitivity, suggesting increased bladder permeability could represent an etiologic factor in both interstitial cystitis-bladder pain syndrome and irritable bowel syndrome.

Methods: We used an animal model of catheterized ovariectomized female rats instilled intravesically with 1 mg/mL PS for 10 minutes that after 24 hours were treated with 1.

Assessing long-term neuroinflammatory responses to encephalopathy using MRI approaches in a rat endotoxemia model.

Sepsis-associated encephalopathy (SAE) induces neuroinflammation, which is associated with cognitive impairment (CI). CI is also correlated with aging. We used contrast-enhanced magnetic resonance imaging (MRI), perfusion MRI, and MR spectroscopy to assess long-term alterations in BBB permeability, microvascularity, and metabolism, respectively, in a rat lipopolysaccharide-induced SAE model.

Therapeutic efficacy of a synthetic epsin mimetic peptide in glioma tumor model: uncovering multiple mechanisms beyond the VEGF-associated tumor angiogenesis.

Binding of epsin ubiquitin-interacting motif (UIM) with ubiquitylated VEGFR2 is a critical mechanism for epsin-dependent VEGFR2 endocytosis and physiological angiogenesis. Deletion of epsins in vessel endothelium produces uncontrolled tumor angiogenesis and retards tumor growth in animal models. The aim of this study is to test the therapeutic efficacy and targeting specificity of a chemically-synthesized peptide, UPI, which compete for epsin binding sites in VEGFR2 and potentially inhibits Epsin-VEGFR2 interaction in vivo, in an attempt to reproduce an epsin-deficient phenotype in tumor angiogenesis.

Homozygous Expression of Mutant ELOVL4 Leads to Seizures and Death in a Novel Animal Model of Very Long-Chain Fatty Acid Deficiency.

Lipids are essential components of the nervous system. However, the functions of very long-chain fatty acids (VLC-FA; ≥ 28 carbons) in the brain are unknown. The enzyme ELOngation of Very Long-chain fatty acids-4 (ELOVL4) catalyzes the rate-limiting step in the biosynthesis of VLC-FA (Agbaga et al.