Sirt4 promotes hypertrophic growth, the generation of fibrosis and cardiac dysfunction by increasing ROS levels upon pathological stimulation. These findings reveal a role of Sirt4 in pathological cardiac hypertrophy, providing a new potential therapeutic strategy for this disease.
Ischemic cerebral infarction represents a significant cause of disability and death worldwide. Caspase-1 is activated by the NLRP3/ASC pathway and inflammasomes, thus triggering pyroptosis, a programmed cell death. In particular, this death is mediated by gasdermin D (GSDMD), which induces secretion of interleukin (IL)-1β and IL-18. Accordingly, inhibition of caspase-1 prevents the development and worsening of multiple neurodegenerative diseases. However, it is not clear whether inhibition of caspase-1 can preserve blood-brain barrier (BBB) integrity following cerebral infarction. This study therefore aimed at understanding the effect of caspase-1 on BBB dysfunction and its underlying mechanisms in permanent middle cerebral artery occlusion (MCAO). Our findings in rat models revealed that expression of caspase-1 was upregulated following MCAO-induced injury in rats. Consequently, pharmacologic inhibition of caspase-1 using vx-765 ameliorated ischemia-induced infarction, neurological deficits, and neuronal injury. Furthermore, inhibition of caspase-1 enhanced the encapsulation rate of pericytes at the ischemic edge, decreased leakage of both Evans Blue (EB) and matrix metalloproteinase (MMP) proteins, and upregulated the levels of tight junctions (TJs) and tissue inhibitors of metalloproteinases (TIMPs) in MCAO-injured rats. This in turn improved the permeability of the BBB. Meanwhile, vx-765 blocked the activation of ischemia-induced pyroptosis and reduced the expression level of inflammatory factors such as caspase-1, NLRP3, ASC, GSDMD, IL-1β, and IL-18. Similarly, vx-765 treatment significantly reduced the expression levels of inflammation-related receptor for advanced glycation end products (RAGE), high-mobility family box 1 (HMGB1), mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB). Evidently, inhibition of caspase-1 significantly improves ischemia-associated BBB permeability and integrity by suppressing pyroptosis activation and the RAGE/MAPK pathway.
Objective: Deep brain stimulation (DBS) has shown promising outcomes as new therapeutic opportunities for patients with treatment-resistant depression (TRD) who do not respond adequately to several consecutive treatments. This study aims to systematically review and conduct a meta-analysis on the efficacy and safety of DBS for TRD.Method: The literature was comprehensively reviewed using Medline, Google scholar, Cochrane library, Embase, and World Health Organization International Clinical Trials Registry Platform until January 2019. The studied outcomes included response, remission, recurrence, and adverse events (AEs) rates, and were reported as the rate ratio (RR) or pooled estimate with a 95% confidence interval (95% CI). Heterogeneity was measured by an I-square test and a sensitive analysis.Results: A total of 17 studies involving 7 DBS targets were included. For efficacy, DBS treatment was statistically beneficial for TRD, and the response, remission, and recurrence rates were 56% (ranging from 43 to 69%), 35% (ranging from 27 to 44%), and 14% (ranging from 4 to 25%), respectively. However, only two randomized-controlled trials (RCTs) considered the invalidity of DBS (RR = 1.45, 95% CI = 0.50–4.21). For safety, the AEs rate was 67% (ranging from 54 to 80%). The AEs were common and moderate, but the problems related to suicide and suicidal ideation should not be underestimated.Conclusion: These findings suggest that DBS for TRD is considered promising, which should be confirmed by well-designed and large sample studies. Future basic research and comprehensive clinical trials are needed to reach better understanding on the mechanisms of action and optimal targeted structure.
Abstract. The aim of this study was to investigate the method and significance of the application of direct electrical stimulation (DES) to the brain mapping of language functions during glioma surgery. A retrospective analysis of clinical data was performed for 91 cases of brain functional area glioma surgery under DES from January 2003 until January 2012. Following cortical electrical stimulation, 88 patients exhibited seizures involving facial or hand movements and 91 cases experienced language disorders such as counting interruption, naming errors or anomia. The most commonly observed areas of counting interruption were distributed on the posterior part of the left anterior central gyrus (47.7%), the operculum of the left inferior frontal gyrus (24.4%) and the triangular part of the left inferior frontal gyrus (12.8%). Postoperative magnetic resonance imaging demonstrated that overall excision was achieved in 53 cases and sub-overall excision was performed in 31 cases. A total of 42 cases (46.2%) exhibited no postoperative neurological dysfunction, 39 cases (42.9%) exhibited brief language dysfunction, 27 cases (29.7%) experienced brief limb movement disorder, and one case appeared to have permanent neurological dysfunction. DES was indicated to be a reliable and noninvasive method for the intraoperative positioning of language areas, and was able to resect gliomas in the language area with maximal safety.
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