Epilepsy is a severe and chronic neurological disease. Edaravone is an effective free radical scavenger and has been reported to prevent neuronal loss induced by Kainate (KA). However, the molecular ...mechanisms by which edaravone inhibits KA-induced neuron injury remain elusive. Seventy adult male Wistar rats were randomly divided into 7 groups. For KA treatment, Kainate (4 μg/kg) were administrated in the right hippocampus CA3 region with sereotactic technique. And for edaravone treatment, the rats were intraperitoneal injection with edaravone (10 mg kg - 1 d – 1). All rats were sacrificed on the seven day after the injection of KA. Histological changes of the hippocampus, CA1, CA3 and CA4 were observed under thionine staining. Histological changes of CA1 and CA3 were divided into the following 4 grades (histological grade,HG) under light microscope. The release of inflammatory cytokines was measured by ELISA assay. The inflammatory proteins and Nrf2 and HO-1 expression were determined by quantitative real time PCR (qRT-PCR) and Western blots analysis. Treatment with edaravone increased the neuronal density and decreased the neuronal damage degree in the CA1, CA3 subfield induced by KA. Besides, edaravone reduced the downregulation of the mRNA and protein expression levels of Nrf2 and HO-1 induced by KA. Moreover, edaravone decreased the levels of NF-κB (P65) and proinflammatory cytokines TNF-α, IL-1β and IL-6 and the inflammatory proteins expression levels, HMGB1, nNOS, iNOS and eNOS in the hippocampus. However, introduction of Nrf2-siRNA and HO-1 inhibitor (Znpp) reversed the effects of edaravone on KA-injected rats. Edaravone can protect hippocampal neurons from damage in KA-induced epilepsy rats through Nrf2/HO-1 pathway.
•Edaravone decreased KA-induced hippocampal neuron damage via Nrf2/HO-1 signaling.•Edaravone protected against KA-induced inflammation in the hippocampus through Nrf2/HO-1 signaling.•Under edaravone treatment, HO-1 was a downstream signaling of Nrf2 in KA-injected rats.
Carotid artery stenosis (CAS) is one of the main risk factors of ischemic stroke (IS), which needs a screening and monitoring biomarker. The study focused on the clinical significance of long ...non-coding RNA (lncRNA) HCG11 in CAS patients aiming to identify a potential therapeutic target for CAS. Serum samples were collected from 70 CAS patients and 80 age- and gender-matched healthy people. HCG11 levels were measured via quantitative real-time PCR (qRT-PCR), and its significance in CAS identification and development prediction was also assessed. HCG11 was enriched in the serum of CAS patients, and serves as a possible biomarker for disease diagnosis with the area under the curve (AUC) of 0.930. Elevated expression of HCG11 was significantly correlated with hypertension, dyslipidemia, and degree of carotid stenosis. HCG11 was highly expressed in severe CAS cases compared to moderate ones, which was positively related to the disease severity. Cox regression analysis determined the close relationship of serum HCG11 with the occurrence of cerebral ischemia events. CAS patients with high HCG11 expression showed a high occurrence rate of cerebral ischemia events. The upregulation of HCG11 could serve as a potential diagnostic biomarker for CAS and is positively related to the disease severity. Serum HCG11 can independently predict the occurrence of following cerebral ischemia events.
Stroke of large-artery atherosclerosis and small-artery occlusion are two main subtypes of stroke according to TOAST classification. The underlying mechanisms of how these two subtypes affect dynamic ...cerebral autoregulation (dCA) might be heterogeneous, resulting in varied clinical conditions and outcomes. We therefore studied the pattern of dCA in these two subtypes.
Forty-one patients with acute unilateral middle cerebral artery (MCA) territory stroke (15 with ipsilateral large-artery atherosclerosis and 26 with small-artery occlusion) and 20 healthy volunteers were enrolled. Non-invasive continuous cerebral blood flow velocity and arterial blood pressure were recorded simultaneously from each subject in supine position using transcranial Doppler on MCA bilaterally and servo-controlled plethysmograph on the middle finger, respectively. Transfer function analysis was applied to derive autoregulatory parameters, gain, phase difference (PD), and slope of step response.
In the large-artery atherosclerosis group, PD in affected hemisphere was 42.9±18.5 degree, which is significantly lower than the unaffected hemisphere (72.4±29.9 degree, P<0.01), and the healthy group (P<0.01). However, PD is similar in the unaffected hemisphere and healthy group (P>0.1). In the small-artery occlusion group, PD in the affected hemisphere was similar to that in the contralateral hemisphere (33.8±17.9 vs. 32.6±21.1 degree, P>0.1), both sides were significantly lower than the healthy group (all P<0.001).The results of the slope of step response agree with the findings in PD.
DCA in different subtypes of acute ischemic stroke is heterogeneous, which might be attributed to the varied pathologic changes of cerebral blood vessels.
In clinical practice, sera creatinine level is regarded as a crucial biomarker for the diagnosis, staging and monitoring of kidney disease. An amperometric biosensor is rapid, accurate, and ...cost-effective, with a portability and a simple operation. Herein, we report for the firsttime a disposable, printed amperometric biosensor for the clinical evaluation of creatinine in renal function detection. The sensor is constructed based on Prussian blue/carbon-graphite paste as the working electrode and the immobilization of creatinine amidohydrolase, creatine amidinohydrolase and sarcosine oxidase. The creatinine biosensor shows a linear detection range from 0.05 to 1.4 mM with a detection time of about 3 min. In addition, the sensor shows a high stability that can maintain above 86% of the initial activity after being stored for over 4 months. Moreover, the sensor shows almost the same results as those with the Jaffe method for measuring the real blood samples. We anticipate that the creatinine biosensor could be widely used in the medical and healthcare areas, especially for at-home testing and onsite medical examinations.
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•The work reports for the first time the development of a disposable, miniaturized and cost-effective creatinine biosensor.•The biosensor shows an accurate, sensitive and rapid determination of serum creatinine in renal function detection.•The biosensor demonstrates a similar detection performance to the Jeff Method that is used in hospital.•The biosensor exhibits a great potential for the at-home testing and the on-site medical examination.
Uric acid is produced via the purine metabolism pathway, and an abnormal level of uric acid could lead to serious diseases and complications, such as gout, renal and cardiovascular diseases. A rapid, ...convenient and accurate detection of uric acid is highly desired for healthcare applications. Here, we report a screen-printed amperometric biosensor for uric acid based on a composite ink consisting of graphene, Prussian blue and rhodium/carbon catalyst. The working electrode is printed by a graphene/Prussian blue ink and a Rhodium/carbon ink sequentially with drying in between. The linear detection range for uric acid is 0.04-0.8 mM with a response time of 30 s and a detection limit of 0.55 μM. The biosensor could be stored in a refrigerator at 4 C° for 80 days without a significant decrease in response. Further, compared to the detection results from the clinical standard method, the relative error of the biosensor is within 20% for detecting uric acid in human blood samples. It is anticipated that this work could advance exciting fundamental studies for the uric acid sensing devices, as well as the clinical applications for the detection of uric acid.
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