Architectural control of metabolic plasticity in epithelial cancer cells.

Metabolic plasticity enables cancer cells to switch between glycolysis and oxidative phosphorylation to adapt to changing conditions during cancer progression, whereas metabolic dependencies limit plasticity. To understand a role for the architectural environment in these processes we examined metabolic dependencies of cancer cells cultured in flat (2D) and organotypic (3D) environments. Here we show that cancer cells in flat cultures exist in a high energy state (oxidative phosphorylation), are glycolytic, and depend on glucose and glutamine for growth.

Ventilatory responses to constant load exercise following the inhalation of a short-acting ß-agonist in a laboratory-controlled diesel exhaust exposure study in individuals with exercise-induced bronchoconstriction.

Objective: Individuals with exercise-induced bronchoconstriction (EIB) use ß-agonists to reduce respiratory symptoms during acute exercise. The resultingbronchodilation could increase the dose of inhaled pollutants and impair respiratory function when exercise is performedin air pollution. We aimed to assess respiratory responses in individuals with EIB when completing a cycling bout while being exposed to diesel exhaust (DE) or filtered air (FA) with and without the inhalation of salbutamol (SAL), a short-acting ß-agonist.

Accessible dynamic micropatterns in monolayer cultures via modified desktop xurography.

Micropatterned cell cultures provide an important tool to understand dynamic biological processes, but often require specialized equipment and expertise. Here we present subtractive bioscribing (SuBscribing), a readily accessible and inexpensive technique to generate dynamic micropatterns in biomaterial monolayers on-the-fly. We first describe our modifications to a commercially available desktop xurographer and demonstrate the utility and limits of this system in creating micropatterned cultures by mechanically scribing patterns into a brittle, non-adhesive biomaterial layer.

Developmentally-Inspired Biomimetic Culture Models to Produce Functional Islet-Like Cells From Pluripotent Precursors.

Insulin-producing beta cells sourced from pluripotent stem cells hold great potential as a virtually unlimited cell source to treat diabetes. Directed pancreatic differentiation protocols aim to mimic various stimuli present during embryonic development through sequential changes of culture conditions. This is commonly accomplished by the timed addition of soluble signaling factors, in conjunction with cell-handling steps such as the formation of 3D cell aggregates.

Vascular effects of physical activity are not modified by short-term inhaled diesel exhaust: Results of a controlled human exposure study.

Background: The combined effects of physical activity and air pollution exposure on vascular function are insufficiently understood, particularly after the inhalation of a β-agonist, a vasodilating agent.

Objective: To assess the micro- and macrovascular response to physical activity after β-agonist use while breathing diesel exhaust (DE) in individuals with exercise-induced bronchoconstriction.

Methods: On four exposure visits, eighteen adults inhaled either 400 μg of the β-agonist salbutamol or placebo before resting for 60 min, followed by a 30-min cycling bout.

Controlled clustering enhances PDX1 and NKX6.1 expression in pancreatic endoderm cells derived from pluripotent stem cells.

Pluripotent stem cell (PSC)-derived insulin-producing cells are a promising cell source for diabetes cellular therapy. However, the efficiency of the multi-step process required to differentiate PSCs towards pancreatic beta cells is variable between cell lines, batches and even within cultures. In adherent pancreatic differentiation protocols, we observed spontaneous local clustering of cells expressing elevated nuclear expression of pancreatic endocrine transcription factors, PDX1 and NKX6.

Biomimetic Micropatterned Adhesive Surfaces To Mechanobiologically Regulate Placental Trophoblast Fusion.

The placental syncytiotrophoblast is a giant multinucleated cell that forms a tree-like structure and regulates transport between mother and baby during development. It is maintained throughout pregnancy by continuous fusion of trophoblast cells, and disruptions in fusion are associated with considerable adverse health effects including diseases such as preeclampsia. Developing predictive control over cell fusion in culture models is hence of critical importance in placental drug discovery and transport studies, but this can currently be only partially achieved with biochemical factors.

Meta-Analysis of Time in Therapeutic Range in Continuous-Flow Left Ventricular Assist Device Patients Receiving Warfarin.

Continuous-flow left ventricular assist devices (CF-LVADs) prolong survival in advanced heart failure patients. Anticoagulation control is critical in CF-LVAD patients due to increased thromboembolic and bleeding risk. We assessed the quality of INR control in CF-LVAD patients measured by time in therapeutic range (TTR).

Stem cells: to be born great, achieve greatness, or have greatness thrust upon them?

Induced pluripotent stem cells (iPSCs) have opened new doors in providing an ethical, patient-specific cell source towards tissue engineering. Developing these therapies involves the production of reprogrammed iPSCs, expanding them while maintaining pluripotency, then differentiating them into functional tissues. To bring these therapies to the clinic, efficient and GMP-compliant manufacturing methods are required.

Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic.

Itraconazole (ITZ) is an FDA-approved member of the triazole class of antifungal agents. Two recent drug repurposing screens identified ITZ as a promising anticancer chemotherapeutic that inhibits both the angiogenesis and hedgehog (Hh) signaling pathways. We have synthesized and evaluated first- and second-generation ITZ analogues for their anti-Hh and antiangiogenic activities to probe more fully the structural requirements for these anticancer properties.

Cerebral metabolism after forced or voluntary physical exercise.

The pathophysiology of stroke, a leading cause of morbidity and mortality, is still in the process of being understood. Pre-ischemic exercise has been known to be beneficial in reducing the severity of stroke-induced brain injury in animal models. Forced exercise with a stressful component, rather than voluntary exercise, was better able to induce neuroprotection.