Endothelial cell leakage occurs in several diseases. Intracellular junctions and transcellular fashion are involved. The definite regulatory mechanism is complicated and not fully elucidated. The alpha subunit of the heterotrimeric G-stimulatory protein (Gsα) mediates receptor-stimulated production of cyclic adenosine monophosphate (cAMP). However, the role of Gsα in the endothelial barrier remains unclear. In this study, mice with knockout of endothelial-specific Gsα (GsαECKO) were generated by crossbreeding Gsαflox/flox mice with Cdh5-CreERT2 transgenic mice, induced in adult mice by tamoxifen treatment. GsαECKO mice displayed phenotypes of edema, anemia, hypoproteinemia and hyperlipoproteinemia, which indicates impaired microvascular permeability. Mechanistically, Gsα deficiency reduces the level of endothelial plasmalemma vesicle-associated protein (PLVAP). In addition, overexpression of Gsα increased phosphorylation of cAMP response element-binding protein (CREB) as well as the mRNA and protein levels of PLVAP. CREB could bind to the CRE site of PLVAP promoter and regulate its expression. Thus, Gsα might regulate endothelial permeability via cAMP/CREB-mediated PLVAP expression.
Post-ischemic angiogenesis is a vital pathophysiological process in diseases such as peripheral arterial disease (PAD), heart ischemia, and diabetic retinopathy. The molecular mechanisms of post-ischemic angiogenesis are complicated and not fully elucidated. The G protein stimulatory alpha subunit (Gsα) is essential for hormone-stimulated cyclic adenosine monophosphate (cAMP) production and is an important regulator for many physiological processes. In the present study, we investigated the role of endothelial Gsα in post-ischemic angiogenesis by generating adult mice with endothelial-specific Gsα deficiency (GsαECKO). GsαECKO mice had impaired blood flow recovery after hind limb ischemic injury, and reduced neovascularization in allograft transplanted tumors. Mechanically, Gsα could regulate the expression of angiogenic factor with G patch and FHA domains 1 (AGGF1) through cAMP/CREB pathway. AGGF1 plays a key role in angiogenesis and regulates endothelial cell proliferation as well as migration. Knockdown of CREB or mutation of the CRE site on the AGGF1 promoter led to reduced AGGF1 promoter activity. In addition, knockdown of AGGF1 reduced the proangiogenic effect of Gsα in endothelial cells, and overexpression of AGGF1 reversed the impaired angiogenesis in GsαECKO mice in vivo. The finding may prove useful in designing new therapeutic targets for treatments of post-ischemic angiogenesis-related diseases.
Background This study aimed to identify the types of quality of life (QoL) based on the five dimensions of the EQ-5D and predict factors affecting QoL. Methods A multistage stratified cluster sampling survey was conducted among the staff of 12 general hospitals, 1965 nurses completed the survey, and the data were analysed using SPSS 26.0 and Mplus 8.3 for latent analysis. Results Three latent classes of QoL were identified: low-level (2.8%), pain and discomfort (7.6%), medium-level (47.1%), and high-level (42.5%). The types and characteristics of QoL differed among these latent classes. The low-level group had the lowest EQ visual analogue scale (EQ-VAS) score (F = 75.217, P < 0.001) and the highest K10 score (F = 61.90, P < 0.001). Moreover, increased age (OR = 0.819, 95% CI: 0.817–0.973), never having drunk alcohol (OR = 0.107, 95% CI: 0.023, 0.488), and increased EQ-VAS scores (OR = 0.935, 95% CI: 0.919, 0.952) were protective factors for quality of life, while working in obstetrics and gynaecology (OR = 6.457, 95% CI:1.852, 22.512) and higher K10 scores (OR = 1.153, 95% CI: 1.100, 1.209) were risk factors for quality of life. Conclusion The results indicated significant heterogeneity in the types of QoL and identified predictors of QoL. These findings provide basic information for the development of nursing interventions to improve quality of life and identified specific characteristics that should be considered during intervention development.
Background: This study explored how coping styles mediate the relationship between sleep status and quality of life among night shift nurses. Methods: A multistage stratified cluster sampling survey was conducted among staff at a general hospital from November 2019 to January 2020. A total of 1,170 night shift nurses completed the Pittsburgh Sleep Quality Index (PSQI), EuroQol five-dimensions (EQ-5D), and Simplified Coping Style Questionnaire (SCSQ). Respectively, these measures were used to assess sleep quality, the quality of life, and coping styles. Results: The total sleep status was positively correlated with the quality of life (r = 0.31, P < 0.05) and negative coping (r = 0.18, P < 0.05), negatively correlated with positive coping (r = -0.05, P < 0.05). Negative coping was positively correlated with the quality of life (r = 0.42, P < 0.05). According to the path analysis, sleep status had a positive effect on negative coping (β = 0.18, P < 0.05) and quality of life (β = 0.11, P < 0.05), negative effect on positive coping (β = -0.05, P < 0.05); positive coping had a negative effect on quality of life (β = -0.03, P < 0.05), while negative coping had a positive effect on quality of life (β = 0.02, P < 0.05). Conclusions: Coping style partially mediated the relationship between sleep status and quality of life. This suggests that interventions targeting coping styles may benefit night shift nurses, as such an approach can ultimately enhance the quality of life by improving sleep.
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