miR-27a-3p regulates expression of intercellular junctions at the brain endothelium and controls the endothelial barrier permeability

Background The brain endothelial barrier permeability is governed by tight and adherens junction protein complexes that restrict paracellular permeability at the blood-brain barrier (BBB). Dysfunction of the inter-endothelial junctions has been implicated in neurological disorders such as multiple sclerosis, stroke and Alzheimer’s disease. The molecular mechanisms underlying junctional dysfunction during BBB impairment remain elusive. MicroRNAs (miRNAs) have emerged as versatile regulators of the BBB function under physiological and pathological conditions, and altered levels of BBB-associated microRNAs were demonstrated in a number of brain pathologies including neurodegeneration and neuroinflammatory diseases. Among the altered micro-RNAs, miR-27a-3p was found to be downregulated in a number of neurological diseases characterized by loss of inter-endothelial junctions and disruption of the barrier integrity. However, the relationship between miR-27a-3p and tight and adherens junctions at the brain endothelium remains unexplored. Whether miR-27a-3p is involved in regulation of the junctions at the brain endothelium remains to be determined. Methods Using a gain-and-loss of function approach, we modulated levels of miR-27a-3p in an in-vitro model of the brain endothelium, key component of the BBB, and examined the resultant effect on the barrier paracellular permeability and on the expression of essential tight and adherens junctions. The mechanisms governing the regulation of junctional proteins by miR-27a-3p were also explored. Results Our results showed that miR-27a-3p inhibitor increases the barrier permeability and causes reduction of claudin-5 and occludin, two proteins highly enriched at the tight junction, while miR-27a-3p mimic reduced the paracellular leakage and increased claudin-5 and occludin protein levels. Interestingly, we found that miR-27-3p induces expression of claudin-5 and occludin by downregulating Glycogen Synthase Kinase 3 beta (GSK3ß) and activating Wnt/ ß-catenin signaling, a key pathway required for the BBB maintenance. Conclusion For the first time, we showed that miR-27a-3p is a positive regulator of key tight junction proteins, claudin-5 and occludin, at the brain endothelium through targeting GSK3ß gene and activating Wnt/ß-catenin signaling. Thus, miR-27a-3p may constitute a novel therapeutic target that could be exploited to prevent BBB dysfunction and preserves its integrity in neurological disorders characterized by impairment of the barrier’s function

Probable Hydrochlorothiazide-Induced Myopericarditis: First Case Reported

Hydrochlorothiazide has never been reported as a reason for myopericarditis. An African American female, with past history of hypertension, coronary artery disease, and sulfa allergy, presented with indolent onset and retrosternal chest pain which was positional, pleuritic, and unresponsive to sublingual nitroglycerin. Her medications included hydrochlorothiazide (HCTZ) which was started three months ago for uncontrolled hypertension. Significant laboratory parameters included erythrocyte sedimentation rate (ESR) of 47 mm/hr and peak troponin of 0.26 ng/mL. Transthoracic echocardiogram (TTE) revealed preserved ejection fraction with no segmental wall motion abnormalities; however, it showed moderate pericardial effusion without tamponade physiology. We hypothesize that this myopericarditis could be due to HCTZ allergic reaction after all other common etiologies have been ruled out. There is a scarcity of the literature regarding HCTZ as an etiology for pericardial disease, with only one case reported as presumed hydrochlorothiazide-induced pericardial effusion. Management involves discontinuation of HCTZ and starting anti-inflammatory therapy

Ipsilateral reexpansion pulmonary edema after drainage of a spontaneous pneumothorax: a case report

We report a case of ipsilateral reexpansion pulmonary edema occurring after the insertion of a chest tube in a patient with spontaneous pneumothorax. The patient received supplemental oxygen via a non-rebreather face mask to compensate for hypoxemia. 24 hours after the acute event, the patient recovered completely without residual hypoxemia. Reexpansion pulmonary edema after the insertion of a thoracic drainage for pneumothorax or pleural effusion is a rare complication with a high mortality rate up to 20%. It should be considered in case of hypoxemia following the insertion of a chest tube. The exact pathophysiology leading to this complication is not known. Risk factors for reexpansion pulmonary edema should be evaluated and considered prior to the insertion of chest tubes. Treatment is supportive

Work–Family Conflict and Job Outcomes Among Prison Officers in Ghana: A Test of Mediation and Moderation Processes

This study examines the mediating effect of job stress and the moderating effect of job autonomy on the relationship between work-to-family conflict (WFC) and job satisfaction and organizational commitment. It uses cross-sectional data from 1062 prison officers sampled from 31 prison establishments in Ghana. The results of structural equation modelling (SEM) analysis showed that WFC was negatively associated with job satisfaction and organizational commitment. Job stress significantly mediated the influence of WFC on job satisfaction and organizational commitment. The negative influence of WFC on job satisfaction and organizational commitment was less for prison officers with higher levels of job autonomy than for those with lower levels of autonomy. These findings suggest the need for correctional organizations to adopt family-friendly measures that facilitate officers’ ability to integrate their work and family responsibilities