Lundsgaardtermansen2287

Z Iurium Wiki

In this report, we discussed the functions of SOX2 in both stem and cancer cells, as well as how this powerful regulator can be used to control cell fate.Transient Potential Receptor Ankyrin 1 (TRPA1) is a ligand-gated cation channel that responds to endogenous and exogenous irritants. TRPA1 is expressed on multiple cell types throughout the lungs, but previous studies have primarily focused on TRPA1 stimulation of airway sensory nerves. We sought to understand the integrated physiologic airway response to TRPA1 stimulation. The TRPA1 agonists allyl isothiocyanate (AITC) and cinnamaldehyde (CINN) were tested in sedated, mechanically ventilated guinea pigs in vivo. Reproducible bronchoconstrictions were induced by electrical stimulation of the vagus nerves. Animals were then treated with intravenous AITC or CINN. AITC and CINN were also tested on isolated guinea pig and mouse tracheas, and post- mortem human trachealis muscle strips in an organ bath. Tissues were contracted with methacholine, histamine, or potassium chloride, then treated with AITC or CINN. Some airways were pre-treated with TRPA1 antagonists, the cyclooxygenase inhibitor indomethacin, the EP2 receptor antagonist PF04418948, or tetrodotoxin. AITC and CINN blocked vagally-mediated bronchoconstriction in guinea pigs. Pretreatment with indomethacin completely abolished the airway response to TRPA1 agonists. Similarly, AITC and CINN dose-dependently relaxed precontracted guinea pig, mouse, and human airways in the organ bath. AITC and CINN-induced airway relaxation required TRPA1, prostaglandins, and PGE2 receptor activation. TRPA1-induced airway relaxation did not require epithelium or tetrodotoxin-sensitive nerves. Finally, AITC blocked airway hyperreactivity in two animal models of allergic asthma. These data demonstrate that stimulation of TRPA1 causes bronchodilation of intact airways and suggest that the TRPA1 pathway is a potential pharmacologic target for bronchodilation.We previously demonstrated that the combined exposure of human pulmonary microvascular endothelial cells (HPMECs) to morphine and viral protein(s) results in the oxidative stress mediated induction of autophagy leading to shift in the cells from early apoptotic to apoptosis-resistant proliferative status associated with the angio-proliferative remodeling observed in pulmonary arterial hypertension (PAH). In this study, we tried to delineate the major source of HIV-1 protein Tat and morphine induced oxidative burst in HPMECs and its consequences on vascular remodeling and PAH in an in-vivo model. We observed switch from the initial increased expression of NADPH oxidase (NOX)2 in response to acute treatment of morphine and HIV-Tat to later increased expression of NOX4 on chronic treatment in the endoplasmic reticulum of HPMECs without any alterations in the mitochondria. Furthermore, NOX dependent induction of autophagy was observed to play a pivotal role in regulating the endothelial cell-survival. Our in-vivo findings showed significant increase in pulmonary vascular remodeling, right ventricular systolic pressure and Fulton index in HIV-transgenic rats on chronic administration of morphine. This was associated with increased oxidative stress in lung tissues as well as in rat pulmonary microvascular endothelial cells. Additionally, endothelial cells from morphine treated HIV-Tg rats demonstrated increased expression of NOX2 and NOX4 proteins; inhibition of which ameliorated their increased survival upon serum starvation. In conclusion, this study describes NADPH oxidases as one of the main players in the oxidative stress mediated endothelial dysfunction on the dual hit of HIV-viral protein(s) and opioids.Air-liquid interface (ALI) cultures are extensively used ex vivo models to study the epithelium of patients with chronic respiratory diseases. However, the in vitro conditions impose a milieu different from that encountered in the patient, in vivo, and the degree to which this alters gene expression remains unclear. In this study, we employed RNA sequencing and compared the transcriptome of fresh brushings of nasal epithelial cells with those which have been cultured in ALI from the same patients. We observed a strong correlation between cells cultured at the ALI and cells obtained from the brushed nasal epithelia and 96% of expressed genes showed similar expression profiles, although there was greater similarity between the brushed samples. We observed that while ALI model does provide an excellent representation of the in vivo airway epithelial transcriptome for mechanistic studies, there are several pathways effected by the change in milieu.Endotracheal intubation is a vital component of many rat in vivo experiments to secure the airway and allow controlled ventilation. Even in the hands of experienced researchers, however, the procedure remains technically challenging. The safest and most reliable way for human intubation is by video laryngoscopy. Previous attempts to apply this technique in rodents have been complicated and expensive. We hereby describe a novel, non-invasive method to safely intubate rats orally by video laryngoscopy, thus avoiding the need for a surgical tracheostomy. By repurposing a commercially available ear wax removal device, visualization of the rat larynx can be significantly enhanced. Due to its small diameter, integrated illumination, and a powerful camera with adequate focal length, the device has all necessary properties for exploring the upper airway of a rat. After identifying the vocal cords by video laryngoscopy, the insertion of an endotracheal tube (a 14G intravenous catheter) into the trachea under constant visual control is facilitated by using PE50 tubing as a stylet (Seldinger technique). The procedure has been performed more than 60 times in our laboratory; all intubations were successful on the first attempt, and no adverse events were observed. We conclude that the described procedure is a simple and effective way to intubate a rat non-invasively, using inexpensive and commercially available equipment.Tooth-brushing is one of the most important health behaviors to teach children considering potentially serious ramifications of poor dental health. However, children's tooth-brushing behavior is affected by various developmental factors. The aim of this cross-sectional study was to investigate factors related to the tooth-brushing behavior of children adopting the Theory of Planned Behavior. A preliminary elicitation study with 33 primary school students identified underlying beliefs related to tooth-brushing intentions. This data was analysed, synthesized, and incorporated into the development of survey items for three age-appropriate, closed-ended questionnaires administered to 709 primary public school students. click here Path analyses using structural equation modelling were used to discover the structural relationships among the direct and indirect determinants of tooth-brushing behaviors, and path estimates and the model fit were calculated. Social recognition, peer influence, self-motivating strategies, and cognitive aspects of tooth-brushing were found to become more influential in facilitating behavioral intention with age.

Autoři článku: Lundsgaardtermansen2287 (Madsen Thuesen)