Wilkersonmckee7635

Ischemic stroke, which is the second highest cause of death and the leading cause of disability, represents ~71% of all strokes globally. Some studies have found that the key elements of the pathobiology of stroke is immunity and inflammation. Microglia are the first line of defense in the nervous system. After stroke, the activated microglia become a double-edged sword, with distinct phenotypic changes to the deleterious M1 types and neuroprotective M2 types. buy AG-270 Therefore, ways to promote microglial polarization toward M2 phenotype after stroke have become the focus of attention in recent years. In this review, we discuss the process of microglial polarization, summarize the alternation of signaling pathways and epigenetic regulation that control microglial polarization in ischemic stroke, aiming to find the potential mechanisms by which microglia can be transformed into the M2 polarized phenotype.Current treatments targeting amyloid beta in Alzheimer's disease (AD) have minimal efficacy, which results in a huge unmet medical need worldwide. Accumulating data suggest that brain mitochondrial dysfunction play a critical role in AD pathogenesis. Targeting cellular mechanisms associated with mitochondrial dysfunction in AD create a novel approach for drug development. This study investigated the effects of nilotinib, as a selective tyrosine kinase inhibitor, in astroglia derived from 3xTg-AD mice versus their C57BL/6-controls. Parameters included oxygen consumption rates (OCR), ATP, cytochrome c oxidase (COX), citrate synthase (CS) activity, alterations in oxidative phosphorylation (OXPHOS), nuclear factor kappa B (NF-κB), key regulators of mitochondrial dynamics (mitofusin (Mfn1), dynamin-related protein 1 (Drp1)), and mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator1-alpha (PGC-1α), calcium/calmodulin-dependent protein kinase II (CaMKII), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)). Nilotinib increased OCR, ATP, COX, Mfn1, and OXPHOS levels in 3xTg astroglia. No significant differences were detected in levels of Drp1 protein and CS activity. Nilotinib enhanced mitochondrial numbers, potentially through a CaMKII-PGC1α-Nrf2 pathway in 3xTg astroglia. Additionally, nilotinib-induced OCR increases were reduced in the presence of the NF-κB inhibitor, Bay11-7082. The data suggest that NF-κB signaling is intimately involved in nilotinib-induced changes in bioenergetics in 3xTg brain astroglia. Nilotinib increased translocation of the NF-κB p50 subunit into the nucleus of 3xTg astroglia that correlates with an increased expression and activation of NF-κB. The current findings support a role for nilotinib in improving mitochondrial function and suggest that astroglia may be a key therapeutic target in treating AD.In the last decades, the strong increase in the proportion of older people worldwide, and the increased prevalence of age associated degenerative diseases, have put a stronger focus on aging biology. In spite of important progresses in our understanding of the aging process, an integrative view is still lacking and there is still need for efficient anti-aging interventions that could improve healthspan, reduce incidence of age-related disease and, eventually, increase the lifespan. Interestingly, some compounds from traditional medicine have been found to possess anti-oxidative and anti-inflammatory properties, suggesting that they could play a role as anti-aging compounds, although in depth in vivo investigations are still scarce. In this study we used one the major aging model organisms, Drosophila melanogaster, to investigate the ability of four herb extracts (HEs Dendrobium candidum, Ophiopogon japonicum, Ganoderma sinense and Panax notoginseng) widely used in traditional Chinese medicine (TCM) to slow down aging and improve healthspan of aged animals. Combining multiple approaches (stress resistance assays, lifespan and metabolic measurements, functional heart characterizations and behavioral assays), we show that these four HEs provide in vivo protection from various insults, albeit with significant compound-specific differences. Importantly, extracts of P. notoginseng and G. sinense increase the healthspan of aging animals, as shown by increased activity during aging and improved heart function. In addition, these two compounds also provide protection in a Drosophila model of Huntington's disease (HD), suggesting that, besides their anti-aging properties in normal individuals, they could be also efficient in the protection against age-related diseases.Although revascularization rates after endovascular thrombectomy for large vessel acute ischemic stroke (AIS) are high (71%), only 46% of patients achieve functional independence at 90 days. The present study was designed to explore a new method for predicting the functional prognosis of AIS patients after endovascular recanalization. A total of 200 anterior circulation stroke patients who received endovascular therapy were enrolled. Logistic regression analysis of clinical characteristics on functional independence were performed. The predictive power of sub-items in National Institute of Health stroke scale (NIHSS) and the combination of NIHSS consciousness and Alberta Stroke Program Early CT Score (ASPECTS) on functional independence were assessed by Receiver Operating Characteristic (ROC) curves and the latter was compared with 3 previously published prediction models by AUC (the area under ROC curve). The AUC for the NIHSS consciousness score to predict functional independence was higher than whole NIHSSn.Acute ischemic stroke due to basilar artery occlusion (BAO) carries a very poor prognosis. Functional outcomes in BAO patients undergoing endovascular therapy (EVT) may differ according to the specific pathological mechanisms. We aimed to explore the impact of the underlying pathological mechanisms on prognosis at 90-days and long-term follow-up in BAO patients treated with EVT. We analyzed consecutive BAO patients undergoing EVT from December 2012 to December 2018 at a single center (Xuanwu Hospital). Patients were classified into either an intracranial atherosclerotic disease (ICAD) group or an embolic group according to the corresponding angiographic findings. The baseline characteristics and functional outcomes were compared between the two groups. Multivariable logistic regression analysis was performed. Among the 167 patients enrolled, 78 patients (46.7%) were in the ICAD group and 89 patients (53.3%) were assigned to the embolic group. Overall, 149 patients (89.2%) achieved successful reperfusion post-EVT.