American journal of physiology. Lung cellular and molecular physiology
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Am. J. Physiol. Lung Cell Mol. Physiol. · Nov 2014
GSK3β-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury.
Although AMP-activated protein kinase (AMPK) is involved in regulating carbohydrate and lipid metabolism, activated AMPK also plays an anti-inflammatory role in many cell populations. However, despite the ability of AMPK activation to diminish the severity of inflammatory responses, previous studies have found that AMPK activity is diminished in LPS-treated neutrophils and also in lungs of mice with LPS-induced acute lung injury (ALI). Since GSK3β participates in regulating AMPK activity, we examined potential roles for GSK3β in modulating LPS-induced activation of neutrophils and macrophages and in influencing severity of ALI. ⋯ Inhibition of GSK3β activity delayed IκBα degradation and diminished expression of the proinflammatory TNF-α in LPS-stimulated neutrophils and macrophages. In vivo, inhibition of GSK3β decreased the severity of LPS-induced lung injury as assessed by development of pulmonary edema, production of TNF-α and MIP-2, and release of the alarmins HMGB1 and histone 3 in the lungs. These results show that inhibition of AMPK by GSK3β plays an important contributory role in enhancing LPS-induced inflammatory responses, including worsening the severity of ALI.
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Am. J. Physiol. Lung Cell Mol. Physiol. · Nov 2014
ReviewMolecular biomarkers in idiopathic pulmonary fibrosis.
Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. ⋯ Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF.
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Am. J. Physiol. Lung Cell Mol. Physiol. · Nov 2014
Biography Historical ArticleHumphry Davy, nitrous oxide, the Pneumatic Institution, and the Royal Institution.
Humphry Davy (1778-1829) has an interesting place in the history of respiratory gases because the Pneumatic Institution in which he did much of his early work signaled the end of an era of discovery. The previous 40 years had seen essentially all of the important respiratory gases described, and the Institution was formed to exploit their possible value in medical treatment. Davy himself is well known for producing nitrous oxide and demonstrating that its inhalation could cause euphoria and heightened imagination. ⋯ Ultimately Davy became president of the Royal Society, a remarkable honor for somebody with such humble origins. Another of his important contributions was to introduce Michael Faraday (1791-1867) to science. Faraday became one of the most illustrious British scientists of all time.