Background: Asthma is one of the most common chronic respiratory disease states in the United States and poses a large economic burden. The Global Initiative for Asthma updated its clinical guidelines to recommend low-dose inhaled corticosteroids (ICSs)-formoterol as the preferred reliever option in the treatment of asthma. Randomized controlled trials show lower exacerbation rates in patients using an ICS-formoterol inhaler as a reliever compared with patients using a short-acting β-agonist-based reliever.
View Article and Find Full Text PDFIn pre-eclampsia models, nicotinamide (NAM) has protective effects in pre-eclampsia and is being evaluated as a therapeutic nutraceutical in clinical studies. NAM undergoes extensive hepatic metabolism by NAM N-methyltransferase to methylnicotinamide (MNA), which is subsequently metabolized to methyl-2-pyridone-5-carboxamide (M2PY) by aldehyde oxidase. However, the pharmacokinetics of NAM and its major metabolites has never been studied in pregnant individuals.
View Article and Find Full Text PDFCystic fibrosis (CF) is a rare, life-threatening disease that results in severe respiratory, digestive, and metabolic problems. Elexacaftor/tezacaftor/ivacaftor is an oral drug that was approved by the US Food and Drug Administration (FDA) on October 21, 2019, after demonstrating clinical improvements compared with previous CF transmembrane conductance regulator modulators. Use of CF transmembrane conductance regulator modulators has improved CF care, but their high costs exceed commonly used cost-effectiveness thresholds.
View Article and Find Full Text PDFPrecise developmental control of jaw length is critical for survival, but underlying molecular mechanisms remain poorly understood. The jaw skeleton arises from neural crest mesenchyme (NCM), and we previously demonstrated that these progenitor cells express more bone-resorbing enzymes including () when they generate shorter jaws in quail embryos versus longer jaws in duck. Moreover, if we inhibit bone resorption or we can increase jaw length.
View Article and Find Full Text PDFMicroRNAs (miRNAs) are key posttranscriptional regulators of osteoblastic commitment and differentiation. miR-433-3p was previously shown to target Runt-related transcription factor 2 (Runx2) and to be repressed by bone morphogenetic protein (BMP) signaling. Here, we show that miR-433-3p is progressively decreased during osteoblastic differentiation of primary mouse bone marrow stromal cells in vitro, and we confirm its negative regulation of this process.
View Article and Find Full Text PDFPrecisely altering gene expression is critical for understanding molecular processes of embryogenesis. Although some tools exist for transgene misexpression in developing chick embryos, we have refined and advanced them by simplifying and optimizing constructs for spatiotemporal control. To maintain expression over the entire course of embryonic development we use an enhanced transposon system that efficiently integrates sequences into the host genome.
View Article and Find Full Text PDFSerum glucocorticoids play a critical role in synchronizing circadian rhythm in peripheral tissues, and multiple mechanisms regulate tissue sensitivity to glucocorticoids. In the skeleton, circadian rhythm helps coordinate bone formation and resorption. Circadian rhythm is regulated through transcriptional and post-transcriptional feedback loops that include microRNAs.
View Article and Find Full Text PDFSub-individual biomarkers are sub-lethal biological responses commonly used in the assessment of wildlife exposure to environmental contaminants. In this study, we examined the activity of glutathione-s-transferase (GST) and lactate dehydrogenase (LDH), and metallothionein (MT) concentrations among captive-raised alligator hatchlings, wild-caught juveniles, and wild-caught adults. Juveniles and adults were collected from three locations in Florida (USA) with varying degrees of contamination (i.
View Article and Find Full Text PDFFew gene markers selectively identify mesenchymal progenitor cells inside the bone marrow. We have investigated a cell population located in the mouse bone marrow labeled by Connective Tissue Growth Factor reporter expression (CTGF-EGFP). Bone marrow flushed from CTGF reporter mice yielded an EGFP+ stromal cell population.
View Article and Find Full Text PDFReduced IGF-I is associated with low bone mass in humans and mice. C3H/He/J (C3H) mice have higher skeletal IGF-I and greater bone mass than C57BL/6J (B6). We hypothesized that strain-related genotypic differences in Igf1 affected skeletal function.
View Article and Find Full Text PDFExposure to cadmium poses a threat to human health, including increased susceptibility to developing the bone disease osteoporosis. Despite its recognized importance as an environmental toxin, little is known about how cadmium directly impacts bone-forming osteoblasts. We previously reported that cadmium induces apoptosis in human osteoblast-like Saos-2 cells.
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