Cerebral ischemia is a major cause of brain dysfunction, neuroinflammation and oxidative stress have been implicated in the pathophysiological process of cerebral ischemia/reperfusion injury. Celastrol is a potent inhibitor of inflammation and oxidative stress that has little toxicity. The present study was designed to evaluate whether celastrol has neuroprotective effects through anti-inflammatory and antioxidant actions, and to elucidate the possible involved mechanisms in transient global cerebral ischemia reperfusion (tGCI/R) rats. Celastrol (1, 2, or 4 mg/kg) was administrated intraperitoneally immediately after reperfusion and the effect of celastrol on reverting spatial learning and memory impairment was determined by Morris water maze (MWM) task. Inflammatory response and oxidative stress, hippocampal neuronal damage and glial activation, and HMGB1/NF-κB signaling pathway proteins were also examined. Our results indicated that celastrol dose-dependently reduced hippocampal and serum concentration of proinflammatory markers (TNF-α, IL-1β, and IL-6) and oxidative stress marker (MDA), whereas the anti-inflammatory marker IL-10 and antioxidant markers (GSH, SOD, and CAT) were increased significantly in celastrol treated tGCI/R rats. Celastrol alleviated apoptotic neuronal death, inhibited reactive glial activation and proliferation and improved ischemia-induced neurological deficits. Simultaneously, we found that mechanisms responsible for the neuroprotective effect of celastrol could be attributed to its anti-inflammatory and antioxidant actions via inhibiting HMGB1/NF-κB signaling pathway. These findings provide a proof of concept for the further validation that celastrol may be a superior candidate for the treatment of severe cerebral ischemic patients in clinical practice in the future.
Background
Electroacupuncture (EA) has been commonly used to treat stroke in China. However, the underlying mechanism remains largely unknown. The present study investigated the neuroprotective effects of EA in middle cerebral artery occlusion (MCAO) rats and elucidated the possible anti-inflammatory mechanisms.
Material/Methods
In this study, modified neurological severity scoring (mNSS) was used to assess neurological deficits, and TTC staining and brain water content were measured to evaluate the degree of brain damage. HE staining, Nissl staining, and TUNEL staining were employed to evaluate apoptotic neuronal death. Molecular biological methods were used to measure the levels of miR-233, NLRP3, caspase-1, IL-1β, and IL-18 in the peri-infarct cortex.
Results
Our results showed that EA treatment significantly decreased the neurological deficit score and infarct volume of MCAO rats. The level of miR-223 was increased, while the levels of NLRP3, caspase-1, IL-1β, and IL-18 were decreased in the peri-infarct cortex of EA-treated MCAO rats. However, the neuroprotective effect of EA was partially blocked by antagomir-223.
Conclusions
These data suggest that EA treatment can alleviate neuroinflammation by inhibiting the miR-223/NLRP3 pathway, thus playing a neuroprotective role in MCAO in rats.
Background: In China, electroacupuncture (EA) is used to treat the symptoms of ischemic stroke. However, the mechanisms involved in the effects of EA in cerebral ischemia remain to be investigated. This study aimed to investigate the molecular mechanism underlying the effects of EA in a rat model of cerebral ischemia-reperfusion injury (CIRI) induced by middle cerebral artery occlusion (MCAO). Material/Methods: Seventy-five male Sprague-Dawley rats were divided into five groups: the sham group (with sham surgery), the model group (the MCAO model), the EA group (treated with EA), the EA control group, and the EA+antagomir-223-3p group. Rats in the model of CIRI underwent MCAO for 90 minutes. EA was performed on the second postoperative day and was performed at the Waiguan (TE5) and Zusanli (ST36) acupoints. The rat brains were evaluated for structural and molecular markers. Results: EA treatment significantly upregulated the expression of microRNA-223 (miR-223), NESTIN, and NOTCH1, and downregulated the expression of PTEN in the subventricular zone (SVZ) and hippocampus. The luciferase reporter assay supported that PTEN was a direct target of miR-223, and antagomiR-223-3p reversed the effects of EA and reduced the increase in NESTIN and inhibition of PTEN expression associated with EA treatment. There was a negative correlation between PTEN expression and the number of neural stem cells (NSCs). Conclusions: In a rat model of CIRI following MCAO, EA activated the NOTCH pathway, promoted the expression of miR-223, increased the number of NSCs, and reduced the expression of PTEN.
Background. Osteoporotic vertebral compression fractures (OVCFs) are common health issues in the elderly that cause chronic pain in over one-third of patients. This study was sought to evaluate the efficacy and safety of acupuncture for alleviating pain caused by OVCFs. Methods. We performed a search of 8 electronic databases for publications from the inception to 30th March 2021. Eligible studies were randomized clinical trials (RCTs) that evaluated the effect of acupuncture for the treatment of OVCFs. Two investigators evaluated literature quality and extracted data independently. RevMan V.5.4.1 was used for data analyses, with pooled risk estimates presented as mean difference (MD) or relative risk (RR) along with corresponding 95% confidence intervals (CIs), as appropriate. Results. Fourteen RCTs involving 1,130 patients were included in this meta-analysis. Compared with the control group, acupuncture showed a greater benefit on pain reduction caused by OVCFs (1 week: MD = −1.26, 95% CI: (−1.82,−0.70); 1 month: MD = −1.63, 95% CI: (−1.82,−1.43); 6 months: MD = −1.13, 95% CI: (−1.55, −0.70)). Acupuncture treatment was also associated with fewer adverse events, lower ODI index, and higher bone density than the control group (safety: (RR: 0.30, 95% CI: 0.12–0.75); ODI: MD = −3.19, 95% CI: (−5.20, −1.19); bone density: MD = 0.15, 95% CI: (0.05, 0.26)). The GRADE quality of these results was assessed as low or very low. Conclusions. Compared with the control treatment, acupuncture was more effective and safer in relieving the pain caused by OVCF and made a greater improvement on patient’s ODI score and bone density. Given the low level of our study evidence, future high-quality studies are needed to verify our study findings.
Neutron detection technology is a powerful method for characterizing fundamental and industrial materials such as magnetic materials, nanomaterials, polymers, and biological substances. Compact pulsed neutron source is desired since the traditional way of producing high-yield neutrons depends mainly on large-scale accelerator or fission reactor. Here, we propose a scheme to generate high-yield pulsed neutron source by using >100 fs relativistic laser pulse interacting with micro-structure assisted pitcher-catcher target. Three-dimensional particle-in-cell and Monte Carlo hybrid simulations demonstrate that energetic deuterium ion beam with a cutoff energy of 75 MeV and 7.23% laser-to-deuterium energy conversion efficiency can be obtained with a laser pulse of intensity 1.37e20 W/cm2, duration 330 fs, power 34 TW and energy 6.7 J. When they strike the following lithium fluoride converter of thickness 2 cm, a large number of neutrons are thus produced via 7Li(d,n) nuclear reaction. The neutron yield is up to 10e9 and its pulse duration is as short as 20 ps. This scheme could be realized in laboratories with current hundreds-of-terawatt or multi-petawatt laser facilities
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