A paradigm of endothelium-protective and stent-free anti-restenotic therapy using biomimetic nanoclusters.

Drug-eluting stents are the most commonly employed method to control post-angioplasty restenosis. Unfortunately, they exacerbate life-threatening stent thrombosis because of endothelium damage caused by both drug and stenting. To solve this major medical problem, an endothelium-protective and stent-free anti-restenotic method is highly desirable.

Dielectric properties of 3D-printed materials for anatomy specific 3D-printed MRI coils.

Additive manufacturing provides a low-cost and rapid means to translate 3D designs into the construction of a prototype. For MRI, this type of manufacturing can be used to construct various components including the structure of RF coils. In this paper, we characterize the material properties (dielectric constant and loss tangent) of several common 3D-printed polymers in the MRI frequency range of 63-300 MHz (for MRI magnetic field strengths of 1.

Temporal Analysis of Factors Associated with EAT-10 in Outpatients with Oropharyngeal Dysphagia from a Tertiary Care Clinic.

Self-perception of disease is increasingly recognized as a determinant of health. The Eating Assessment Tool-10 (EAT-10) is a functional health status questionnaire that measures the symptomatic severity of dysphagia from the patient's perspective. The objective of this work was to identify factors (demographics, clinical variables, swallowing physiology, health-related quality of life) associated with longitudinal change in EAT-10 scores in outpatients with oropharyngeal dysphagia at a multi-disciplinary, tertiary care clinic.

Analysis of Combined Transcriptomes Identifies Gene Modules that Differentially Respond to Pathogenic Stimulation of Vascular Smooth Muscle and Endothelial Cells.

Smooth muscle cells (SMCs) and endothelial cells (ECs) are vital cell types composing the vascular medial wall and the atheroprotective inner lining, respectively. Current treatments for cardiovascular disease inhibit SMC hyperplasia but compromise EC integrity, predisposing patients to thrombosis. Therapeutics targeting SMCs without collateral damage to ECs are highly desirable.

Author Correction: Synuclein and dopamine: the Bonnie and Clyde of Parkinson's disease.

In the version of this article initially published, the molecular mass of synuclein was given as 140 kDa instead of ~14 kDa. The error has been corrected in the HTML and PDF versions of the article.

Overcoming Resistance to Cetuximab with Honokiol, A Small-Molecule Polyphenol.

Overexpression and activation of the EGFR have been linked to poor prognosis in several human cancers. Cetuximab is a mAb against EGFR that is used for the treatment in head and neck squamous cell carcinoma (HNSCC) and metastatic colorectal cancer. Unfortunately, most tumors have intrinsic or will acquire resistance to cetuximab during the course of therapy.

Role of the sigma-1 receptor chaperone in rod and cone photoreceptor degenerations in a mouse model of retinitis pigmentosa.

Background: Retinitis pigmentosa (RP) is the most common inherited retinal degenerative disease yet with no effective treatment available. The sigma-1 receptor (S1R), a ligand-regulated chaperone, emerges as a potential retina-protective therapeutic target. In particular, pharmacological activation of S1R was recently shown to rescue cones in the rd10 mouse, a rod Pde6b mutant that recapitulates the RP pathology of autonomous rod degeneration followed by secondary death of cones.

APEX2-enhanced electron microscopy distinguishes sigma-1 receptor localization in the nucleoplasmic reticulum.

The sigma-1 receptor (Sig1R) is an endoplasmic reticulum chaperonin that is attracting tremendous interest as a potential anti-neurodegenerative target. While this membrane protein is known to reside in the inner nuclear envelope (NE) and influences transcription, apparent Sig1R presence in the nucleoplasm is often observed, seemingly contradicting its NE localization. We addressed this confounding issue by applying an antibody-free approach of electron microscopy (EM) to define Sig1R nuclear localization.

PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma.

Distinguishing malignant peritoneal mesothelioma (MPM) from serous carcinoma involving the peritoneum remains a diagnostic challenge, particularly in small biopsy and cytology specimens. In this distinction, PAX8 expression has been regarded as a specific marker of serous carcinoma. In addition, BAP1 loss is reportedly specific to MPM, in the distinction from both benign mesothelial lesions and ovarian serous tumors (OSTs).

Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets.

O-Linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS).

Hyperglycemia attenuates receptor activator of NF-κB ligand-induced macrophage activation by suppressing insulin signaling.

Background: Although male gender, aging, hypertension, dyslipidemia, and smoking are common risk factors for abdominal aortic aneurysm, diabetes mellitus is an independent negative risk factor. In aneurysm tissue, matrix metalloproteinases (MMPs) expressed by activated macrophages degrades extracellular matrix proteins. In our previous experimental study, we demonstrated that the aneurysmal formation and macrophage activity were suppressed by inhibiting mimicking hyperglycemia (HG) through upregulation of glucose-sensing nuclear receptor, Nr1h2.

Predicting Future Hip Fractures on Routine Abdominal CT Using Opportunistic Osteoporosis Screening Measures: A Matched Case-Control Study.

Objective: Hip fracture is a major consequence of low bone mineral density, which is treatable but underdiagnosed. The purpose of this case-control study is to determine whether lumbar vertebral trabecular attenuation, vertebral compression fractures, and femoral neck T scores readily derived from abdominopelvic CT scans obtained for various indications are associated with future hip fragility fracture.

Materials And Methods: A cohort of 204 patients with hip fracture (130 women and 74 men; mean age, 74.

Cleanliness of Canal Walls following Gutta-Percha Removal with Hand Files, RaCe and RaCe plus XP-Endo Finisher Instruments: A Photographic Analysis.

Introduction: Gutta-percha must be removed from the root canal space during retreatment to ensure a more favorable outcome. The aim of this study was to compare the efficacy of hand instruments, RaCe and RaCe plus XP-endo finisher instruments in removal of gutta-percha from root canal walls during retreatment.

Methods And Materials: Thirty single-rooted premolars were prepared, obturated, and divided into three groups according to retreatment method; in group 1, retreatment was carried out by hand instruments, while in groups 2 and 3 retreatment was done using RaCe rotary files alone or accompanied by XP-endo finisher instruments, respectively.

Epigenetic intervention with a BET inhibitor ameliorates acute retinal ganglion cell death in mice.

Purpose: The bromo and extraterminal (BET) epigenetic "reader" family is becoming an appealing new therapeutic target for several common diseases, yet little is known of its role in retinal neurodegeneration. We explored the potential of BET inhibition in the protection of retinal ganglion cells (RGCs).

Methods: To test the therapeutic effect of JQ1, an inhibitor highly selective for the BET family of proteins, we used an acute RGC damage model induced by N-methyl-D-aspartic acid (NMDA) excitotoxicity.

A Genome-wide Analysis of Human Pluripotent Stem Cell-Derived Endothelial Cells in 2D or 3D Culture.

A defined protocol for efficiently deriving endothelial cells from human pluripotent stem cells was established and vascular morphogenesis was used as a model system to understand how synthetic hydrogels influence global biological function compared with common 2D and 3D culture platforms. RNA sequencing demonstrated that gene expression profiles were similar for endothelial cells and pericytes cocultured in polyethylene glycol (PEG) hydrogels or Matrigel, while monoculture comparisons identified distinct vascular signatures for each cell type. Endothelial cells cultured on tissue-culture polystyrene adopted a proliferative phenotype compared with cells cultured on or encapsulated in PEG hydrogels.

Peeking into Sigma-1 Receptor Functions Through the Retina.

This review discusses recent advances towards understanding the sigma-1 receptor (S1R) as an endogenous neuro-protective mechanism in the retina , a favorable experimental model system. The exquisite architecture of the mammalian retina features layered and intricately wired neurons supported by non-neuronal cells. Ganglion neurons, photoreceptors , as well as the retinal pigment epithelium, are susceptible to degeneration that leads to major retinal diseases such as glaucoma , diabetic retinopathy , and age-related macular degeneration (AMD), and ultimately, blindness.

Restenosis Inhibition and Re-differentiation of TGFβ/Smad3-activated Smooth Muscle Cells by Resveratrol.

To date, there is no periadventitial drug delivery method available in the clinic to prevent restenotic failure of open vascular reconstructions. Resveratrol is a promising anti-restenotic natural drug but subject to low bioavailability when systemically administered. In order to reconcile these two prominent issues, we tested effects of periadventitial delivery of resveratrol on all three major pro-restenotic pathologies including intimal hyperplasia (IH), endothelium impairment, and vessel shrinkage.

Effect of dental restorative materials on total antioxidant capacity and calcium concentration of unstimulated saliva.

Background: To evaluate the effect of dental amalgam and composite restorations on total antioxidant capacity (TAC) and calcium (Ca) ion concentration of unstimulated saliva.

Material And Methods: Forty-eight children aged 6-10 years selected and divided into three groups of sixteen (8 males, 8 females). In group A and B, samples consisted of two class II dental composite or amalgam restorations, while in group C samples were caries-free (control group).

Photoreceptor protection via blockade of BET epigenetic readers in a murine model of inherited retinal degeneration.

Background: The bromodomain and extraterminal domain (BET) family proteins (BET2, BET3, and BET4) "read" (bind) histone acetylation marks via two distinct bromodomains (Brom1 and Brom2) facilitating transcriptional activation. These epigenetic "readers" play crucial roles in pathogenic processes such as inflammation. The role of BETs in influencing the degenerative process in the retina is however unknown.

An intraocular drug delivery system using targeted nanocarriers attenuates retinal ganglion cell degeneration.

Glaucoma is a common blinding disease characterized by loss of retinal ganglion cells (RGCs). To date, there is no clinically available treatment directly targeting RGCs. We aim to develop an RGC-targeted intraocular drug delivery system using unimolecular micelle nanoparticles (unimNPs) to prevent RGC loss.

Hippocampal α-Synuclein in Dementia with Lewy Bodies Contributes to Memory Impairment and Is Consistent with Spread of Pathology.

Despite considerable research to uncover them, the anatomic and neuropathologic correlates of memory impairment in dementia with Lewy bodies (DLB) remain unclear. While some studies have implicated Lewy bodies in the neocortex, others have pointed to α-synuclein pathology in the hippocampus. We systematically examined hippocampal Lewy pathology and its distribution in hippocampal subfields in 95 clinically and neuropathologically characterized human cases of DLB, finding that α-synuclein pathology was highest in two hippocampal-related subregions: the CA2 subfield and the entorhinal cortex (EC).

Systematic identification of Ctr9 regulome in ERα-positive breast cancer.

Background: We had previously identified Ctr9, the key scaffold subunit of the human RNA polymerase II (RNAPII) associated factor complex (PAFc), as a key factor regulating a massive ERα target gene expression and ERα-positive breast cancer growth. Furthermore, we have shown that knockdown of Ctr9 reduces ERα protein stability and decreases the occupancy of ERα and RNAPII at a few ERα-target loci. However, it remains to be determined whether Ctr9 controls ERα-target gene expression by regulating the global chromatin occupancy of ERα and RNAPII in the presence of estrogen.

F-FLT PET/CT imaging in patients with advanced solid malignancies treated with axitinib on an intermittent dosing regimen.

Purpose: This study utilizes FLT PET/CT imaging to characterize changes in tumor cell proliferation and vasculature during intermittent treatment with VEGR-TKI axitinib.

Methods: Patients with metastatic solid malignancies underwent 3-week treatment cycles with axitinib (7 and 5 mg BID for safety and pharmacodynamic cohorts, respectively). Cycles consisted of 2 weeks of treatment (dosing period) followed by a 1-week treatment break (washout period).