Ischemic stroke is characterized by permanent or transient obstruction of blood flow, which initiates a cascading pathological process, starting from acute ATP loss and ionic imbalance to subsequent membrane depolarization, glutamate excitotoxicity, and calcium overload. These initial events are followed by neuroinflammation and oxidative stress, eventually causing neuronal neurosis and apoptosis. Complicated interplays exist between these steps happening across various stages, which not only represent the complicated nature of ischemic pathology but also warrant a detailed delineation of the underlying molecular mechanisms to develop better therapeutic options. In the present study, we examined the neuroprotective effects of polydatin against ischemic brain injury using a rat model of permanent middle cerebral artery occlusion (MCAO). Our results demonstrated that polydatin treatment reduced the infarction volume and mitigated the neurobehavioral deficits, sequentially rescued neuronal apoptosis. Ischemic stroke induced an elevation of neuroinflammation and reactive oxygen species, which could be attenuated by polydatin
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the reduced activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. In addition, polydatin upregulated the endogenous antioxidant nuclear factor erythroid 2-related factor 2, heme oxygenase-1, the thioredoxin pathway, and eventually reversed ischemic-stroke-induced elevation of ROS and inflammation in ischemic cortical tissue. The diverse and broad actions of polydatin suggested that it could be a multiple targeting neuroprotective agent in ameliorating the detrimental effects of MCAO, such as neuroinflammation, oxidative stress, and neuronal apoptosis. As repetitive clinical trials of neuroprotectants targeting a single step of stroke pathological process have failed previously, our results suggested that a neuroprotective strategy of acting at different stages may be more advantageous to intervene in the vicious cycles in MCAO.
Five flavonoids, namely (-)-epicatechin-3-O-β-glucopyranoside (1), 5-hydroxy-3-(4-hydroxylphenyl)pyrano[3,2-g]chromene-4(8H)-one (2), 6-(p-hydroxybenzyl)taxifolin-7-O-β-D-glucoside (tricuspid) (3), quercetin-3-O-α-glucopyranosyl-(1 → 2)-β-D-glucopyranoside (4) and (-)-epicatechin(2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-chromene-3,5,7-triol (5), were isolated from the leaves of mango (Mangifera indica L.). Antifungal activity of these compounds was evaluated against five fungal species, namely Alternaria alternata (Fr.) Keissler, Aspergillus fumigatus Fresenius, Aspergillus niger van Tieghem, Macrophomina phaseolina (Tassi) Goid. and Penicillium citrii. Six concentrations, namely 100, 300, 500, 700, 900 and 1000 ppm of each of the five flavonoids were employed by means of the poisoned medium technique. All concentrations of the five test flavonoids significantly suppressed fungal growth. However, the specificity of different test compounds was evident against different fungal species. In general, antifungal activity of the flavonoids was gradually increased by increasing their concentrations. The highest concentration (of 1000 ppm) of compounds 1-5 reduced the growth of different target fungal species by 63-97%, 56-96%, 76-99%, 76-98% and 82-96%, respectively.
Stroke is the leading cause of morbidity and mortality worldwide. About 87% of stroke cases are ischemic, which disrupt the physiological activity of the brain, thus leading to a series of complex pathophysiological events. Despite decades of research on neuroprotectants to probe for suitable therapies against ischemic stroke, no successful results have been obtained, and new alternative approaches are urgently required in order to combat this pathological torment. To address these problems, drug repositioning/reprofiling is explored extensively. Drug repurposing aims to identify new uses for already established drugs, and this makes it an attractive commercial strategy. Nuclear factor-kappa beta (NF-κB) is reported to be involved in many physiological and pathological conditions, such as neurodegeneration, neuroinflammation, and ischemia/reperfusion (I/R) injury. In this study, we examined the neuroprotective effects of atorvastatin, cephalexin, and mycophenolate against the NF-κB in ischemic stroke, as compared to the standard NF-κB inhibitor caeffic acid phenethyl ester (CAPE). An in-silico docking analysis was performed and their potential neuroprotective activities in the in vivo transient middle cerebral artery occlusion (t-MCAO) rat model was examined. The percent (%) infarct area and 28-point composite neuro score were examined, and an immunohistochemical analysis (IHC) and enzyme-linked immunosorbent assay (ELISA) were further performed to validate the neuroprotective role of these compounds in stroke as well as their potential as antioxidants. Our results demonstrated that these novels NF-κB inhibitors could attenuate ischemic stroke-induced neuronal toxicity by targeting NF-κB, a potential therapeutic approach in ischemic stroke.
An Al 0.1 CoCrFeNi high-entropy alloy (HEA) with a face-centered cubic structure in the as-cast and the recrystallized states is investigated. The mean grain size of the as-cast HEA is 14 times larger than that of the recrystallized HEA. The tension tests reveal that deformation twinning is the main mechanism dominating the plastic deformation of two HEAs. With a decrease in the grain size, twin spacing increases, and twin thickness decreases, which results in a low twinning activity. The twinning activity of the recrystallized HEA is strongly inhibited by grain refinement, which degrades the promotion of twinning on the strain-hardening ability and the tensile ductility. IMPACT STATEMENT Grain refinement on strain hardening and twinning in a high-entropy alloy (HEA) is investigated, which is associated with the nanotwin substructure. Grain refinement decreases the twin thickness, and increases the twin spacing.
Functionalized diarylcarbenes are excellent reactive intermediates suitable for the direct surface modification of organic polymers, and these may be used to introduce urea and thiourea functions onto polystyrene at loading levels of up to 2.3 x 10(13) molecules/cm(2). These functions are capable of the reversible binding and release of peroxide at loading levels of up to 0.6 mmol/g and give polymers that display biocidal activity against a spectrum of gram-positive and gram-negative bacteria.
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