Epac1 inhibition as a novel cardioprotective strategy: lights and shadows on GRK5 canonical and non-canonical functions
β1-adrenergic receptors (β1AR) are members of the super-family of G protein-coupled receptors (GPCR) and major regulators of cardiac function. β1AR stimulation leads to G protein-mediated generation of the second messenger cyclic adenosine monophosphate (cAMP) and activation of effectors such as cAMP-dependent Protein Kinase A (PKA) or Exchange Proteins Activated by cAMP (Epac) (Figure 1). In addition, β1AR stimulation activates GPCR kinases (GRK) ‘canonical’ pathways,1 regulating β1AR phosphorylation, desensitization, down-regulation, degradation and recycling as well as activation of β-arrestin-dependent, G protein-independent signalling (Figure 1).2 GRK5 non-canonical activities in the nucleus have been also recently demonstrated, and new complexes/interactions between GRK5 and other proteins are being continuously identified.2
CONCLUSIONS: The concept of soldier-centered care often emerges in discussions about optimal physical performance and medical readiness for soldiers. Although soldier-centered care and patient-centered care have similar conceptual underpinning, it is important to clarify the unique physical and medical requirements for soldiers that differentiate soldier-centered care from patient-centered care. Implementing the defining attributes of soldier-centered care in the U.S. Army primary care setting may improve the quality of care and health outcomes for soldiers. When defining performance metrics for primary care models of care...
Authors: Waller SG Abstract Three important but neglected principles of evaluation of global health engagement missions are stakeholder engagement, impact, and relative value. Implementing better M&E programs could be carried out in this fiscal year, without new appropriations or manpower. The result would be cost savings and improved security cooperation. PMID: 31942621 [PubMed - as supplied by publisher]
Publication date: Available online 18 January 2020Source: Clinica Chimica ActaAuthor(s): Guodong Zhao, Yong Ma, Hui Li, Shiming Li, Yun Zhu, Xiaoyu Liu, Shangmin Xiong, Yi Liu, Jin Miao, Sujuan Fei, Minxue Zheng, Xiangwei ZhaoAbstractBackgroundMethylated SFRP2 was previously reported as a non-invasive biomarker for colorectal cancer (CRC) detection with a relatively low sensitivity for early stage CRC. The purpose of this study was to evaluate the performance of a new plasma based CRC screening assay, SpecColon test, which tested methylated SFRP2 and SDC2 simultaneously in a single qPCR reaction, in detecting CRC and advan...
CONCLUSIONS: MHR may be a significant and independent predictor of poor functional outcome in patients with AIS. PMID: 31941849 [PubMed - as supplied by publisher]
Authors: Ieda N, Assadullah, Minabe S, Ikegami K, Watanabe Y, Sugimoto Y, Sugimoto A, Kawai N, Ishii H, Inoue N, Uenoyama Y, Tsukamura H Abstract Accumulating evidence suggests that kisspeptin neurons in the arcuate nucleus (ARC), which coexpress neurokinin B and dynorphin, are involved in gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) pulse generation, while the anteroventral periventricular nucleus (AVPV) kisspeptin neurons are responsible for GnRH/LH surge generation. The present study aims to examine whether GnRH(1-5), a GnRH metabolite, regulates LH release via kisspeptin neurons. GnRH(1-5) was...
In conclusion, caffeine decreased oxidative stress and adipogenesis in GO orbital fibroblasts in vitro. These findings may contribute to the development of new types of caffeine-containing pharmacological agents for use in the management of GO. PMID: 31941844 [PubMed - as supplied by publisher]