204000 research outputs found
Sort by
Transitort und Sakralraum – Konzeptionen der Stadt Akkon in Karten und Texten des Mittelalters
No full textStreamlining malaria prevention recommendations for travellers: current and future approaches
No full textVon den Commons ausgeschlossen. Rechtliche Ungleichheit und kollektive Ressourcenregimes in den eidgenössischen Orten Luzern und Nidwalden, 1550–1800
No full text«Wenn die natürlichste Sache der Welt nicht klappt…» Deutungen und Sinngebung bei unerfülltem Kinderwunsch. Eine religionswissenschaftliche Untersuchung
No full textDiaspora Mobilization Between Democracy and Autocracy – Navigating Voice and Loyalty After Exit in the Tibetan Diaspora in Switzerland and Canada
No full textTranslational research on cognitive impairment in chronic kidney disease
No full textCognitive decline is common in patients with acute or chronic kidney disease. Several areas of brain function can be affected, including short- and long-term memory, attention and inhibitory control, sleep, mood, eating control and motor function. Cognitive decline in kidney disease shares risk factors with cognitive dysfunction in people without kidney disease, such as diabetes, high blood pressure, sedentary lifestyle and unhealthy diet. However, additional kidney-specific risk factors may contribute, such as uremic toxins, electrolyte imbalances, chronic inflammation, acid–base disorders or endocrine dysregulation. Traditional and kidney-specific risk factors may interact to cause damage to the blood–brain barrier, induce vascular damage in the brain and cause neurotoxicity or neuroinflammation. Here, we discuss recent insights into the pathomechanisms of cognitive decline from animal models and novel avenues for prevention and therapy. We focus on a several areas that influence cognition: blood–brain barrier disruption, the role of skeletal muscle, physical activity and the endocrine factor irisin, and the emerging therapeutic role of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. Taken together, these studies demonstrate the importance of animal models in providing a mechanistic understanding of this complex condition and their potential to explain the mechanisms of novel therapies
miR-222 inhibits pathological cardiac hypertrophy and heart failure
No full textAIMS: Physiological cardiac hypertrophy occurs in response to exercise and can protect against pathological stress. In contrast, pathological hypertrophy occurs in disease and often precedes heart failure. The cardiac pathways activated in physiological and pathological hypertrophy are largely distinct. Our prior work demonstrated that miR-222 increases in exercised hearts and is required for exercise-induced cardiac hypertrophy and cardiomyogenesis. Here, we sought to define the role of miR-222 in pathological hypertrophy.
METHODS AND RESULTS: We found that miR-222 also increased in pathological hypertrophy induced by pressure overload. To assess its functional significance in this setting, we generated a miR-222 gain-of-function model through cardiac-specific constitutive transgenic miR-222 expression (TgC-miR-222) and used locked nucleic acid anti-miR specific for miR-222 to inhibit its effects. Both gain- and loss-of-function models manifested normal cardiac structure and function at baseline. However, after transverse aortic constriction (TAC), miR-222 inhibition accelerated the development of pathological hypertrophy, cardiac dysfunction, and heart failure. Conversely, miR-222-overexpressing mice had less pathological hypertrophy after TAC, as well as better cardiac function and survival. We identified p53-up-regulated modulator of apoptosis, a pro-apoptotic Bcl-2 family member, and the transcription factors, Hmbox1 and nuclear factor of activated T-cells 3, as direct miR-222 targets contributing to its roles in this context.
CONCLUSION: While miR-222 is necessary for physiological cardiac growth, it inhibits cardiac growth in response to pressure overload and reduces adverse remodelling and cardiac dysfunction. These findings support the model that physiological and pathological hypertrophy are fundamentally different. Further, they suggest that miR-222 may hold promise as a therapeutic target in pathological cardiac hypertrophy and heart failure
