Deciphering the impacts of modulating the Wnt-planar cell polarity (PCP) pathway on alveolar repair.

Many adult lung diseases involve dysregulated lung repair. Deciphering the molecular and cellular mechanisms that govern intrinsic lung repair is essential to develop new treatments to repair/regenerate the lungs. Aberrant Wnt signalling is associated with lung diseases including emphysema, idiopathic pulmonary fibrosis and pulmonary arterial hypertension but how Wnt signalling contributes to these diseases is still unclear.

Home access to a weight scale in the Hispanic/Latino population attending a community-based free clinic.

Background: Daily weighing has been shown to help with weight management. In primary care, the majority of virtual visits will ask patients about their weight. However, little is known about whether patients, especially those in the Hispanic/Latino population, have access to a weight scale.

A feasibility study for quantitative assessment of cerebrovascular malformations using flutriciclamide ([F]GE-180) PET/MRI.

Aim: Neuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous malformations (CCM). Flutriciclamide ([F]GE-180) is a translocator protein (TSPO) targeting positron emission tomography (PET) tracer, developed for imaging neuroinflammation. The objectives of this study were to describe characteristics of flutriciclamide uptake in different brain tissue regions in CCM patients compared to controls, and to evaluate flutriciclamide uptake and iron deposition within CCM lesions.

Links of Cytoskeletal Integrity with Disease and Aging.

Aging is a complex feature and involves loss of multiple functions and nonreversible phenotypes. However, several studies suggest it is possible to protect against aging and promote rejuvenation. Aging is associated with many factors, such as telomere shortening, DNA damage, mitochondrial dysfunction, and loss of homeostasis.

A nanoparticle probe for the imaging of autophagic flux in live mice via magnetic resonance and near-infrared fluorescence.

Autophagy-the lysosomal degradation of cytoplasmic components via their sequestration into double-membraned autophagosomes-has not been detected non-invasively. Here we show that the flux of autophagosomes can be measured via magnetic resonance imaging or serial near-infrared fluorescence imaging of intravenously injected iron oxide nanoparticles decorated with cathepsin-cleavable arginine-rich peptides functionalized with the near-infrared fluorochrome Cy5.5 (the peptides facilitate the uptake of the nanoparticles by early autophagosomes, and are then cleaved by cathepsins in lysosomes).

Made by cells for cells - extracellular vesicles as next-generation mainstream medicines.

Current medicine has only taken us so far in reducing disease and tissue damage. Extracellular vesicles (EVs), which are membranous nanostructures produced naturally by cells, have been hailed as a next-generation medicine. EVs deliver various biomolecules, including proteins, lipids and nucleic acids, which can influence the behaviour of specific target cells.

X-ray bi-prism interferometry-A design study of proposed novel hardware.

Purpose: Advances in X-ray phase-contrast imaging can obtain excellent soft-tissue contrast of phase-shift, attenuation, and small-angle scatter. Here, we present fringe patterns for different design parameters of X-ray bi-prism interferometry imaging systems. Our aim is to develop bi-prism interferometry imaging systems with excellent polychromatic performance that produce high-contrast fringes with spatially incoherent X-ray illumination.

Tomography of dark-field scatter including single-exposure Moiré fringe analysis with X-ray biprism interferometry-A simulation study.

Purpose: In this work, we present tomographic simulations of a new hardware concept for X-ray phase-contrast interferometry wherein the phase gratings are replaced with an array of Fresnel biprisms, and Moiré fringe analysis is used instead of "phase stepping" popular with grating-based setups.

Methods: Projections of a phantom consisting of four layers of parallel carbon microfibers is simulated using wave optics representation of X-ray electromagnetic waves. Simulated projections of a phantom with preferential scatter perpendicular to the direction of the fibers are performed to analyze the extraction of small-angle scatter from dark-field projections for the following: (1) biprism interferometry using Moiré fringe analysis; (2) grating interferometry using phase stepping with eight grating steps; and (3) grating interferometry using Moiré fringe analysis.

An Ex Vivo Acid Injury and Repair (AIR) Model Using Precision-Cut Lung Slices to Understand Lung Injury and Repair.

Recent advances in cell culture models like air-liquid interface culture and ex vivo models such as organoids have advanced studies of lung biology; however, gaps exist between these models and tools that represent the complexity of the three-dimensional environment of the lung. Precision-cut lung slices (PCLS) mimic the in vivo environment and bridge the gap between in vitro and in vivo models. We have established the acid injury and repair (AIR) model where a spatially restricted area of tissue is injured using drops of HCl combined with Pluronic gel.

The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling.

VANGL2 is a component of the planar cell polarity (PCP) pathway, which regulates tissue polarity and patterning. The mutation causes lung branching defects due to dysfunctional actomyosin-driven morphogenesis. Since the actomyosin network regulates cell mechanics, we speculated that mechanosignaling could be impaired when VANGL2 is disrupted.

The acid injury and repair (AIR) model: A novel ex-vivo tool to understand lung repair.

Research into mechanisms underlying lung injury and subsequent repair responses is currently of paramount importance. There is a paucity of models that bridge the gap between in vitro and in vivo research. Such intermediate models are critical for researchers to decipher the mechanisms that drive repair and to test potential new treatments for lung repair and regeneration.

In vivo quantitative mapping of human mitochondrial cardiac membrane potential: a feasibility study.

Purpose: Alteration in mitochondrial membrane potential (ΔΨ) is an important feature of many pathologic processes, including heart failure, cardiotoxicity, ventricular arrhythmia, and myocardial hypertrophy. We present the first in vivo, non-invasive, assessment of regional ΔΨ in the myocardium of normal human subjects.

Methods: Thirteen healthy subjects were imaged using [F]-triphenylphosphonium ([F]TPP+) on a PET/MR scanner.

Can Stem Cells Beat COVID-19: Advancing Stem Cells and Extracellular Vesicles Toward Mainstream Medicine for Lung Injuries Associated With SARS-CoV-2 Infections.

A number of medicines are currently under investigation for the treatment of COVID-19 disease including anti-viral, anti-malarial, and anti-inflammatory agents. While these treatments can improve patient's recovery and survival, these therapeutic strategies do not lead to unequivocal restoration of the lung damage inflicted by this disease. Stem cell therapies and, more recently, their secreted extracellular vesicles (EVs), are emerging as new promising treatments, which could attenuate inflammation but also regenerate the lung damage caused by COVID-19.

Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler.

Background: We recently reported a method using positron emission tomography (PET) and the tracer F-labeled tetraphenylphosphonium (F-TPP) for mapping the tissue (i.e., cellular plus mitochondrial) membrane potential (ΔΨ) in the myocardium.

[F]-AV-1451 binding profile in chronic traumatic encephalopathy: a postmortem case series.

Introduction: Chronic traumatic encephalopathy (CTE) is a tauopathy associated to repetitive head trauma. There are no validated in vivo biomarkers of CTE and a definite diagnosis can only be made at autopsy. Recent studies have shown that positron emission tomography (PET) tracer AV-1451 (Flortaucipir) exhibits high binding affinity for paired helical filament (PHF)-tau aggregates in Alzheimer (AD) brains but relatively low affinity for tau lesions in other tauopathies like temporal lobal degeneration (FTLD)-tau, progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD).

Body motion detection and correction in cardiac PET: Phantom and human studies.

Purpose: Patient body motion during a cardiac positron emission tomography (PET) scan can severely degrade image quality. We propose and evaluate a novel method to detect, estimate, and correct body motion in cardiac PET.

Methods: Our method consists of three key components: motion detection, motion estimation, and motion-compensated image reconstruction.

Placenta Stem/Stromal Cell-Derived Extracellular Vesicles for Potential Use in Lung Repair.

Many acute and chronic lung injuries are incurable and rank as the fourth leading cause of death globally. While stem cell treatment for lung injuries is a promising approach, there is growing evidence that the therapeutic efficacy of stem cells originates from secreted extracellular vesicles (EVs). Consequently, EVs are emerging as next-generation therapeutics.

Isolation and Characterization of Extracellular Vesicles from Mesenchymal Stromal Cells.

Extracellular vesicles (EVs) have received immense attention in the past decade for their diverse use in diagnosis and therapeutics. Enhancing our understanding of EVs and increasing the reliability and reproducibility of EV research demands the use of standard isolation procedures and multiple characterization methods. Here we describe the most commonly used EV isolation method involving ultracentrifugation, and various characterization methods that include nanoparticle tracking analysis, atomic force microscopy and electron microscopy, which measure the size, concentration, and morphology of EVs.

Multi-atlas cardiac PET segmentation.

Purpose: We propose a multi-atlas based segmentation method for cardiac PET and SPECT images to deal with the high variability of tracer uptake characteristics in myocardium. In addition, we verify its performance by comparing it to the manual segmentation and single-atlas based approach, using dynamic myocardial PET.

Methods: Twelve left coronary artery ligated SD rats underwent ([F]fluoropentyl) triphenylphosphonium salt PET/CT scans.

High-fidelity probing of the structure and heterogeneity of extracellular vesicles by resonance-enhanced atomic force microscopy infrared spectroscopy.

Extracellular vesicles (EVs) are highly specialized nanoscale assemblies that deliver complex biological cargos to mediate intercellular communication. EVs are heterogeneous, and characterization of this heterogeneity is paramount to understanding EV biogenesis and activity, as well as to associating them with biological responses and pathologies. Traditional approaches to studying EV composition generally lack the resolution and/or sensitivity to characterize individual EVs, and therefore the assessment of EV heterogeneity has remained challenging.

Shank and Zinc Mediate an AMPA Receptor Subunit Switch in Developing Neurons.

During development, pyramidal neurons undergo dynamic regulation of AMPA receptor (AMPAR) subunit composition and density to help drive synaptic plasticity and maturation. These normal developmental changes in AMPARs are particularly vulnerable to risk factors for Autism Spectrum Disorders (ASDs), which include loss or mutations of synaptic proteins and environmental insults, such as dietary zinc deficiency. Here, we show how Shank2 and Shank3 mediate a zinc-dependent regulation of AMPAR function and subunit switch from GluA2-lacking to GluA2-containing AMPARs.

None of us is the same as all of us: resolving the heterogeneity of extracellular vesicles using single-vesicle, nanoscale characterization with resonance enhanced atomic force microscope infrared spectroscopy (AFM-IR).

Extracellular vesicles (EVs) are highly specialized, nanoscale messengers that deliver biological signals and in doing so mediate intercellular communication. Increasing evidence shows that within populations of EVs, important properties including morphology, membrane composition, and content vary substantially. This heterogeneity arises in response to the nature, state, and environmental conditions of the cell source.

Greater cellular stiffness in fibroblasts from patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease involving degenerative breathing capacity. Fibrotic disease is driven by dysregulation in mechanical forces at the organ, tissue, and cellular level. While it is known that, in certain pathologies, diseased cells are stiffer than healthy cells, it is not known if fibroblasts derived from patients with IPF are stiffer than their normal counterparts.

Tailoring the properties of a hypoxia-responsive 1,8-naphthalimide for imaging applications.

Sensing hypoxia in tissues and cell models can provide insights into its role in disease states and cell development. Fluorescence imaging is a minimally-invasive method of visualising hypoxia in many biological systems. Here we present a series of improved bioreductive fluorescent sensors based on a nitro-naphthalimide structure, in which selectivity, photophysical properties, toxicity and cellular uptake are tuned through structural modifications.