scholarly journals The Next Step in the Treatment of Stroke

2021 ◽  
Vol 11 ◽  
Author(s):  
Nathanael Matei ◽  
Justin Camara ◽  
John H. Zhang

Although many patients do not receive reperfusion therapy because of delayed presentation and/or severity and location of infarct, new reperfusion approaches are expanding the window of intervention. Novel application of neuroprotective agents in combination with the latest methods of reperfusion provide a path to improved stroke intervention outcomes. We examine why neuroprotective agents have failed to translate to the clinic and provide suggestions for new approaches. New developments in recanalization therapy in combination with therapeutics evaluated in parallel animal models of disease will allow for novel, intra-arterial deployment of therapeutic agents over a vastly expanded therapeutic time window and with greater likelihood success. Although the field of neuronal, endothelial, and glial protective therapies has seen numerous large trials, the application of therapies in the context of newly developed reperfusion strategies is still in its infancy. Given modern imaging developments, evaluation of the penumbra will likely play a larger role in the evolving management of stroke. Increasingly more patients will be screened with neuroimaging to identify patients with adequate collateral blood supply allowing for delayed rescue of the penumbra. These patients will be ideal candidates for therapies such as reperfusion dependent therapeutic agents that pair optimally with cutting-edge reperfusion techniques.

2021 ◽  
pp. ASN.2020081177
Author(s):  
Jingping Yang ◽  
Difei Zhang ◽  
Masaru Motojima ◽  
Tsutomu Kume ◽  
Qing Hou ◽  
...  

BackgroundTranscriptional programs control cell fate, and identifying their components is critical for understanding diseases caused by cell lesion, such as podocytopathy. Although many transcription factors (TFs) are necessary for cell-state maintenance in glomeruli, their roles in transcriptional regulation are not well understood.MethodsThe distribution of H3K27ac histones in human glomerulus cells was analyzed to identify superenhancer-associated TFs, and ChIP-seq and transcriptomics were performed to elucidate the regulatory roles of the TFs. Transgenic animal models of disease were further investigated to confirm the roles of specific TFs in podocyte maintenance.ResultsSuperenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. Integration of transcriptome and cistrome data of FOXC1/2 in mice resolved transcriptional regulation in podocyte maintenance. FOXC1/2 regulated differentiation-associated transcription in mature podocytes. In both humans and animal models, mature podocyte injury was accompanied by deregulation of FOXC1/2 expression, and FOXC1/2 overexpression could protect podocytes in zebrafish.ConclusionsFOXC1/2 maintain podocyte differentiation through transcriptional stabilization. The genome-wide chromatin resources support further investigation of TFs’ regulatory roles in glomeruli transcription programs.


2021 ◽  
Vol 22 ◽  
Author(s):  
Zhang Jing ◽  
Wang Rui ◽  
Li Ruihua ◽  
Yu Hao ◽  
Fang Hengtong

: Since the discovery of (2α,3β)-2,3-dihydroxyolean-12-en-28-oic acid, also known as maslinic acid, many studies have examined its biological activity, which has been shown to promote health and resist various diseases. This article focuses on previous research on maslinic acid and mainly reviews its reported effects on cardiovascular diseases, neuroprotection, diabetes, cancer, inflammation, and pathogens. Maslinic acid exerts positive effects on both cell and animal models of disease. Although its mechanism of action has not yet been completely elucidated, maslinic acid is feasible as a nutritional additive and has the potential to be developed as a drug.


2020 ◽  
Vol 23-24 ◽  
pp. 11-16
Author(s):  
Diann Blanset ◽  
Julie Hutt ◽  
Sherry Morgan

PLoS Medicine ◽  
2010 ◽  
Vol 7 (3) ◽  
pp. e1000245 ◽  
Author(s):  
H. Bart van der Worp ◽  
David W. Howells ◽  
Emily S. Sena ◽  
Michelle J. Porritt ◽  
Sarah Rewell ◽  
...  

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