Inhibition of immunoproteasome promotes angiogenesis via enhancing hypoxia-inducible factor-1α abundance in rats following focal cerebral ischaemia

In this study, we identified that inhibition of immunoproteasome LMP2 was able to enhance angiogenesis and facilitate neurological functional recovery in rats after focal cerebral ischemia/reperfusion. In vitro, oxygen-glucose deprivation and reperfusion (OGD/R) significantly enhanced the expression of immunoproteasome LMP2 and proteasome activities in primary culture astrocytes, but these beneficial effects were abolished by knockdown of LMP2 with siRNA transfection. Along with this, protein abundance of HIF-1α was significantly increased by inhibition LMP2 in vivo and in vitro and was associated with angiogenesis and cell fates. However, these beneficial effects were partly abolished by HIF-1α inhibitor 2-methoxyestradiol (2ME). Taken together; this study highlights an important role for inhibition of LMP2 in promoting angiogenesis events in ischemic stroke, and point to HIF-1α as a key mediator of this response, suggesting that immunoproteasome inhibitors may be a promising strategy for stroke treatment.
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research

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AbstractAssociation between serum calcium and magnesium versus hemorrhagic transformation (HT) remains to be identified. A total of 1212 non-thrombolysis patients with serum calcium and magnesium collected within 24  h from stroke onset were enrolled. Backward stepwise multivariate logistic regression analysis was conducted to investigate association between calcium and magnesium versus HT. Calcium and magnesium were entered into logistic regression analysis in two models, separately: model 1, as continuous va riable (per 1-mmol/L increase), and model 2, as four-categorized variable (being collapsed into quartiles). H...
Source: Neurological Sciences - Category: Neurology Source Type: research
ConclusionsART-CAF evaluates the feasibility of selecting high-risk patients suitable for anticoagulation by AF burden combined with CHA2DS2-VASc score after pacemaker implantation and aims to select patients who could benefit from anticoagulation.Trial Registration ChiCTR1800016221
Source: Cardiovascular Drugs and Therapy - Category: Cardiology Source Type: research
ConclusionsMore than a third of patients experiencing a TIA delays medical attention for more than a day, thus critically extending the initiation of stroke preventive treatment. There still seems to be insufficient awareness among lay people that symptoms suggestive of TIA should be considered as an emergency. Additional data and multivariable analyses are needed to define main determinants of patient delay.
Source: Journal of Neurology - Category: Neurology Source Type: research
Authors: Shiyoich A, Kornowski R Abstract Aortic stenosis (AS) is the most common clinical valvular heart disorder that warrants active treatment. Symptomatic and severe AS is associated with increased morbidity and mortality if left untouched. Transcatheter aortic valve implantation (TAVI) is an innovative therapeutic modality approved initially for patients with prohibitive surgical risk and subsequently became a mainstream practice and the preferred treatment modality for many patients with severe AS at high and moderate surgical risk. Consistently global TAVI volumes have increased and indications continue to w...
Source: Minerva Cardioangiologica - Category: Cardiology Tags: Minerva Cardioangiol Source Type: research
CONCLUSIONS: In an unselected population admitted for elective PCI or NSTEMI in real-world clinical practice, administration of a P2Y12 inhibitor only after coronary angiography is associated with a low rate of ischemic and bleeding events at 30 days. PMID: 30012889 [PubMed - as supplied by publisher]
Source: The Journal of Invasive Cardiology - Category: Cardiology Tags: J Invasive Cardiol Source Type: research
Conclusions: Upregulation of miR-298 following ischemic stroke promotes brain injuryin vitro and vivo by inhibiting the Act1/JNK/NF- κB signaling cascade and the downstream autophagy pathway. Therapeutic strategies that target miR-298 could be beneficial for the treatment of ischemic stroke.Cell Physiol Biochem 2018;48:528 –539
Source: Cellular Physiology and Biochemistry - Category: Cytology Source Type: research
This article provides a detailed study design and protocol of HeCES2, an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis. MATERIALS AND METHODS: Recruitment and carotid endarterectomies of the study patients with carotid atherosclerosis were performed from October 2012 to September 2015. After brain and carotid artery imaging, endarterectomised carotid plaques (CPs) and blood samples were collected from 500 patients for detailed biochemical and molecular analyses. Findings to date: We developed a morphological grading for macroscopic characteristic...
Source: Annals of Medicine - Category: Internal Medicine Tags: Ann Med Source Type: research
(MedPage Today) -- Both ischemic and hemorrhagic events increased
Source: MedPage Today Cardiovascular - Category: Cardiology Source Type: news
CONCLUSION: Univariate analyses suggest insulin-like growth factor-binding protein 3 and serum paraoxonase/lactonase 3 are reliable and reproducible biomarkers for TIA status. Logistic regression models indicated L-selectin, apolipoprotein B-100, coagulation factor IX, and thrombospondin-1 to be significant multivariate predictors of TIA. We discuss multivariate feature subset analyses as an exploratory technique to better understand a panel's full predictive potential. PMID: 30010432 [PubMed - as supplied by publisher]
Source: Biomarkers - Category: Research Tags: Biomarkers Source Type: research
Authors: Liu H, He J, Zhong J, Zhang H, Zhang Z, Liu L, Huang Z, Wu Y, Jiang L, Guo Z, Xu R, Chai W, Huo G, Sun X, Cheng C Abstract Background: As a major antioxidant in serum, uric acid (UA) was once considered only as the leading cause of gout; however, recent studies have validated its neuroprotective role in ischemic stroke. Because the potential protective effects of UA in traumatic brain injury (TBI) remain largely unknown, this study investigated the role of UA in TBI in both clinical patients and experimental animals. Methods: In TBI patients, serum UA concentrations were measured within 3 days after injury...
Source: International Journal of Medical Sciences - Category: Biomedical Science Tags: Int J Med Sci Source Type: research
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