Niemann Pick Disease Type C (NP-C), a rare neurogenetic disease with no known cure, is caused by mutations in the cholesterol trafficking protein NPC1. Brain microvascular endothelial cells (BMEC) are thought to play a critical role in the pathogenesis of several neurodegenerative diseases; however, little is known about how these cells are altered in NP-C. In this study, we investigated how NPC1 inhibition perturbs BMEC metabolism in human induced pluripotent stem cell-derived BMEC (hiBMEC).
View Article and Find Full Text PDFBackground: The APOE-ε4 genotype is the highest genetic risk factor for Alzheimer's disease (AD), and exercise training can reduce the risk of AD. Two early pathologies of AD are degradation of tight junctions between brain microvascular endothelial cells (BMEC) and brain glucose hypometabolism. Therefore, the objective of this work was to determine how the APOE-ε4 genotype and serum from exercise trained individuals impacts BMEC barrier function and metabolism.
View Article and Find Full Text PDFObjectives: Histopathology is the core diagnostic tool for cancer in pathology laboratories around the world, but there are disparities in access to diagnostics globally. As recognition of the need for cancer care and treatment grows, especially in the wake of World Health Organization programs for cervical, breast, and pediatric cancers, policymakers and health care funders are seeking tools and processes that allow for the largest number of patients to receive a diagnosis at the lowest cost.
Methods: As histopathology represents the most cost-effective diagnostic method by sheer number of tumor types and volume, understanding the detailed logistics and costs for histology as well as the impactful benefits of economies of scale (ie, larger volumes are less expensive per patient) and scope (ie, the multiple stains available after basic histology sectioning) is paramount to planning an effective publicly funded or government laboratory.
In the body, capillary beds fulfill the metabolic needs of cells by acting as the sites of diffusive transport for vital gasses and nutrients. In artificial tissues, replicating the scale and complexity of capillaries has proved challenging, especially in a three-dimensional context. In order to better develop thick artificial tissues, it will be necessary to recreate both the form and function of capillaries.
View Article and Find Full Text PDFGenerating physiologically relevant red blood cell extracellular vesicles (RBC-EVs) for mechanistic studies is challenging. Herein, we investigated how to generate and isolate high concentrations of RBC-EVs via shear stress and mechanosensitive piezo1 ion channel stimulation. RBC-EVs were generated by applying shear stress or the piezo1-agonist yoda1 to RBCs.
View Article and Find Full Text PDFWithin the biopharmaceutical sector, there exists the need for a contactless multiplex sensor, which can accurately detect metabolite levels in real time for precise feedback control of a bioreactor environment. Reported spectral sensors in the literature only work when fully submerged in the bioreactor and are subject to probe fouling due to a cell debris buildup. The use of a short-wave infrared (SWIR) hyperspectral (HS) cam era allows for efficient, fully contactless collection of large spectral datasets for metabolite quantification.
View Article and Find Full Text PDFIntroduction: Women are at elevated risk for certain cardiovascular diseases, including pulmonary arterial hypertension, Alzheimer's disease, and vascular complications of diabetes. Angiotensin II (AngII), a circulating stress hormone, is elevated in cardiovascular disease; however, our knowledge of sex differences in the vascular effects of AngII are limited. We therefore analyzed sex differences in human endothelial cell response to AngII treatment.
View Article and Find Full Text PDFGlucose transport from the blood into the brain is tightly regulated by brain microvascular endothelial cells (BMEC), which also use glucose as their primary energy source. To study how BMEC glucose transport contributes to cerebral glucose hypometabolism in diseases such as Alzheimer's disease, it is essential to understand how these cells metabolize glucose. Human primary BMEC (hpBMEC) can be used for BMEC metabolism studies; however, they have poor barrier function and may not recapitulate in vivo BMEC function.
View Article and Find Full Text PDFThe number of people diagnosed with neurodegenerative diseases is on the rise. Many of these diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and motor neuron disease, demonstrate clear sexual dimorphisms. While sex as a biological variable must now be included in animal studies, sex is rarely included in models of human neurodegenerative disease.
View Article and Find Full Text PDFThere is a profound need for functional, biomimetic in vitro tissue constructs of the human blood-brain barrier and neurovascular unit (NVU) to model diseases and identify therapeutic interventions. Here, we show that induced pluripotent stem cell (iPSC)-derived human brain microvascular endothelial cells (BMECs) exhibit robust barrier functionality when cultured in 3D channels within gelatin hydrogels. We determined that BMECs cultured in 3D under perfusion conditions were 10-100 times less permeable to sodium fluorescein, 3 kDa dextran, and albumin relative to human umbilical vein endothelial cell and human dermal microvascular endothelial cell controls, and the BMECs maintained barrier function for up to 21 days.
View Article and Find Full Text PDFSchistosomiasis is an acute and chronic disease that affects over 200 million people worldwide, and with over 700 million people estimated to be at risk of contracting this disease, it is a pressing issue in global health. However, research and development (R&D) to develop new approaches to preventing, diagnosing, and treating schistosomiasis has been relatively limited. Praziquantel, a drug developed in the 1970s, is the only agent used in schistosomiasis mass drug administration (MDA) campaigns, indicating a critical need for a diversified therapeutic pipeline.
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