Streptococcus suis (S. suis) serotype 2 is a crucial pathogenic cause of bacterial meningitis, a life-threatening disease with neurological sequelae and high rates of mortality. Inflammation triggered by S. suis infection must be precisely regulated to prevent further tissue damage. As a glucocorticoid anti-inflammatory mediator, Annexin A1 (AnxA1) mainly acts through formyl peptide receptor 2 (Fpr2) to alleviate inflammation in the peripheral system. In this research, we evaluated the roles of AnxA1 and Fpr2 in a mouse model of S. suis meningitis created via intracisternal infection in Fpr2-deficient (Fpr2−/−) and wild-type (WT) mice. We revealed that Fpr2−/− mice were highly susceptible to S. suis meningitis, displaying increased inflammatory cytokine levels, bacterial dissemination, and neutrophil migration compared with the findings in WT mice. Additionally, AnxA1 exerted anti-inflammatory effects through Fpr2, such as attenuation of leukocyte infiltration, inflammatory mediator production, and astrocyte or microglial activation in the brain. Importantly, we found that the anti-migratory function of AnxA1 decreases neutrophil adherence to the endothelium through Fpr2. Finally, an in vitro study revealed that AnxA1 potentially suppresses IL-6 expression through the Fpr2/p38/COX-2 pathway. These data demonstrated that Fpr2 is an anti-inflammatory receptor that regulates neutrophil migration in mice with S. suis meningitis and identified AnxA1 as a potential therapeutic option.
In hearts overexpressing vascular endothelial growth factor B (VEGFB), besides its known angiogenic response, multiple regulatory mechanisms lowered coronary LPL. This was accompanied by limited cardiac lipid metabolite accumulation with an augmentation of cardiac insulin action. Our data for the first time links VEGFB to coronary LPL in regulation of cardiac metabolism. VEGFB may be cardioprotective in metabolic disorders like diabetes.
Background: Postoperative radiocarpal joint stiffness (RJS) is common in patients with distal radius fractures (DRFs). The purpose of this study was to record the incidence of RJS and to determine potential risk factors that may be associated with it. Methods: We retrospectively included a series of patients who suffered from DRFs and underwent volar plate fixation. Patients' basic data, radiographic data, and postoperative data were collected. The incidence of RJS during follow-up was recorded, and both univariate analyses and multivariate logistic regression were used to determine factors associated with it. Results: A total of 119 patients were included in this study. After surgical procedures, there were 42 (35.3%) patients with RJS and 77 (64.7%) patients without. The incidence of RJS after surgical treatment is 35.3%. Multivariate analysis showed that intra-articular fracture (OR, 1.43; 95% CI, 1.13-1.81), pre-operative severe swelling (OR, 1.35; 95% CI, 1.05-1.74), post-operative unsatisfied volar tile (OR, 1.38; 95% CI, 1.01-1.89), and improper rehabilitation exercise (OR, 1.72; 95% CI, 1.18-2.51) were correlated with the incidence of RJS during follow-up. Conclusions: Patients with intra-articular fracture, pre-operative severe swelling, post-operative unsatisfied volar tile, and improper rehabilitation exercise were factors associated with the incidence of wrist stiffness. Preoperative risk notification and postoperative precautions are necessary for relevant patients.
Background
Lipoprotein lipase (LPL)‐derived fatty acid is a major source of energy for cardiac contraction. Synthesized in cardiomyocytes, LPL requires translocation to the vascular lumen for hydrolysis of lipoprotein triglyceride, an action mediated by endothelial cell (EC) release of heparanase. We determined whether flow‐mediated biophysical forces can cause ECs to secrete heparanase and thus regulate cardiac metabolism.
Methods and Results
Isolated hearts were retrogradely perfused. Confluent rat aortic ECs were exposed to laminar flow using an orbital shaker. Cathepsin L activity was determined using gelatin‐zymography. Diabetes was induced in rats with streptozotocin. Despite the abundance of enzymatically active heparanase in the heart, it was the enzymatically inactive, latent heparanase that was exceptionally responsive to flow‐induced release. EC exposed to orbital rotation exhibited a similar pattern of heparanase secretion, an effect that was reproduced by activation of the mechanosensor, Piezo1. The laminar flow‐mediated release of heparanase from EC required activation of both the purinergic receptor and protein kinase D, a kinase that assists in vesicular transport of proteins. Heparanase influenced cardiac metabolism by increasing cardiomyocyte LPL displacement along with subsequent replenishment. The flow‐induced heparanase secretion was augmented following diabetes and could explain the increased heparin‐releasable pool of LPL at the coronary lumen in these diabetic hearts.
Conclusions
ECs sense fluid shear‐stress and communicate this information to subjacent cardiomyocytes with the help of heparanase. This flow‐induced mechanosensing and its dynamic control of cardiac metabolism to generate ATP, using LPL‐derived fatty acid, is exquisitely adapted to respond to disease conditions, like diabetes.
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