Our data indicate that conjugated equine estrogen improves bone quality because it increases the quantity of type I collagen while reducing the quantity of thin collagen fibers. In addition, the combination of CEE and raloxifene or genistein-rich soy extract is not as efficient as CEE itself to improve bone quality.
To describe the progression of parenchymal remodeling and metalloproteinases gene expression in earlier stages of emphysema, mice received porcine pancreatic elastase (PPE) instillation and Control groups received saline solution. After PPE instillation (1, 3, 6 hours, 3 and 21 days) we measured the mean linear intercept, the volume proportion of types I and III collagen, elastin, fibrillin and the MMP-1, -8, -12 and -13 gene expression. We observed an initial decrease in type I (at the 3rd day) and type III collagen (from the 6th hour until the 3rd day), in posterior time points in which we detected increased gene expression for MMP-8 and -13 in PPE groups. After 21 days, the type III collagen fibers increased and the type I collagen values returned to similar values compared to control groups. The MMP-12 gene expression was increased in earlier times (3 and 6 hours) to which we detected a reduced proportion of elastin (3 days) in PPE groups, reinforcing the already established importance of MMP-12 in the breakdown of ECM. Such findings will be useful to better elucidate the alterations in ECM components and the importance of not only metalloelastase but also collagenases in earlier emphysema stages, providing new clues to novel therapeutic targets.
The formation of microthrombi in lung autopsies indicates the involvement of NETs in the immunopathogenesis of severe COVID-19. Therefore, supplements inhibiting NET formation, in association with drugs with fewer adverse effects, should be a relevant strategy to attenuate the disease. Resveratrol (RESV) is a natural polyphenol with an important antiviral and antioxidant role. To modulate neutrophils from patients infected with SARS-CoV-2, we evaluated the in vitro effect of RESV on NET formation. Herein, we investigated 190 patients hospitalized with moderate, severe, and critical symptoms at Hospital das Clínicas, Brazil. We observed that neutrophilia in patients with severe COVID-19 infection is composed of neutrophils with activated profile able to release NET spontaneously. Notably, RESV decreased the neutrophil-activated status and the release of free DNA, inhibiting NET formation even under the specific PMA stimulus. At present, there is no evidence of the role of RESV in neutrophils from patients with COVID-19 infection. These findings suggest that adjunctive therapies with RESV may help decrease the inflammation of viral or bacterial infection, improving patient outcomes.
To evaluate the remodeling of collagen fibers in the articular cartilage of rat ankles, with and without immobilization, after application of muscle stretching protocol. Twenty three Wistar rats were divided into four groups: immobilized (I), n=6; immobilized and stretched (IS), n=6; stretched (S), n=6 and control (C), n=5. The animals in groups I and IS were submitted to immobilization. After the period of immobilization, the animals in groups IS and S were submitted to a muscle stretching protocol. At the end of the experiment, the animals were euthanized and the joints removed, processed and stained with Picrosirius red. The analysis was carried out using a polarized light microscope. The density of collagen fibers were quantified according to the intensity of birefringence displayed. By way of statistical analyses, the right and left hind limbs of the different groups were compared based on the total density of collagen fibers, the density of thick collagen fibers and the density of thin collagen fibers. Immobilization promoted a reduction in density of the thin fibers and of total collagen. The muscle stretching protocol after immobilization promoted a reduction in density of the total collagen and of the thick fibers, but the density of the thin fibers showed the same values as control. The collagen fibers were remodeled by the different stimuli. Immobilization was harmful to the collagen fibers and the muscle stretching protocol only recovered the thin collagen fibers.
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