RESUMO
Post-stroke depression (PSD) is a serious and common complication of stroke, which seriously affects the rehabilitation of stroke patients. To date, the pathogenesis of PSD is unclear and effective treatments remain unavailable. Here, we established a mouse model of PSD through photothrombosis-induced focal ischemia. By using a combination of brain imaging, transcriptome sequencing, and bioinformatics analysis, we found that the hippocampus of PSD mice had a significantly lower metabolic level than other brain regions. RNA sequencing revealed a significant reduction of miR34b-3p, which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E (eIF4E). Furthermore, silencing eIF4E inactivated microglia, inhibited neuroinflammation, and abolished the depression-like behaviors in PSD mice. Together, our data demonstrated that insufficient miR34b-3p after stroke cannot inhibit eIF4E translation, which causes PSD by the activation of microglia in the hippocampus. Therefore, miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.
Assuntos
Animais , Camundongos , Depressão , Fator de Iniciação 4E em Eucariotos/metabolismo , MicroRNAs/metabolismo , Neurônios/metabolismo , Acidente Vascular Cerebral/metabolismoRESUMO
BackgroundWith coronavirus disease 2019 (Covid-19) ravaging the global, concern has been aroused whether discharged Covid-19 patients with reappeared positive nucleic acid test results are infected again. ObjectiveTo analyze the clinical characteristics of discharged Covid-19 patients with reappeared positive nucleic acid test results and to track clinical outcomes of them. MethodsWe extracted clinical data on 938 Covid-19 patients from Wuhan Union Hospital (West Branch), and we obtained information about residual symptoms and nucleic acid tests after discharge through follow-up study. We evaluated the relationship of clinical characteristics and reappeared positive results. Each patient had at least 44 days of follow-up. ResultsOf 938 discharged patients, a total of 58 (6.2%) had reappeared positive nucleic acid test results and 880 remain negative. Among patients over the age of 50, the factors we found to be associated with re-positive results were coronary artery disease (14.1%, vs. 5.5% among those without coronary artery disease; odds ratio, 2.81; 95% confidence interval [CI], 1.28 to 6.15), and hypertension (9.5%, vs. 4.9% among those without hypertension; odds ratio, 2.05; 95% CI, 1.10 to 3.82). As of May 11, 2020, 54 (93.1%) re-positive patients turned negative again while two patients remained positive, and two patients was lost to the second follow-up. ConclusionCoexisting diseases including coronary artery disease and hypertension were substantial risk factors for re-positive outcomes among patients over 50. And most re-positive patients tended to return negative eventually.
RESUMO
Ginsenoside compound K (GCK), the main metabolite of protopanaxadiol constituents of Panax ginseng, easily produces alkali metal adduct ions during mass spectrometry particularly with lithium. Accordingly, we have developed a rapid and sensitive liquid chromatography-tandem mass spectrometric method for analysis of GCK in human plasma based on formation of a lithium adduct. The analyte and paclitaxel (internal standard) were extracted from 50 µL human plasma using methyl tert-butyl ether. Chromatographic separation was performed on a Phenomenex Gemini C18 column (50 mm×2.0 mm; 5 μm) using stepwise gradient elution with acetonitrile-water and 0.2 mmol/L lithium carbonate at a flow rate of 0.5 mL/min. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions at m/z 629→449 for the GCK-lithium adduct and m/z 860→292 for the adduct of paclitaxel. The assay was linear in the concentration range 1.00-1000 ng/mL (r (2)>0.9988) with intra- and inter-day precision of ±8.4% and accuracy in the range of -4.8% to 6.5%. Recovery, stability and matrix effects were all satisfactory. The method was successfully applied to a pharmacokinetic study involving administration of a single GCK 50 mg tablet to healthy Chinese volunteers.
RESUMO
Endothelial progenitor cells(EPCs)are the precursor cells of vascular endothelial cells.EPCs are in bone marrow,peripheral blood and cord blood.They participate in the process of angiogenesis after birth.The stimulation of exogenous and endogenous factors mobilizes bone marrow-derived EPCs into peripheral blood,and participates in the revascularization of ischemic tissue and the process of re-endothelialization of the injured blood vessels.The decreased mmahers and quality of EPCs in blood circulation are one of the most important factors of unfavourable prognosis after ischemic stroke.The transplantation of EPCs may provide a novel therapeutic strategy for the treatment of ischemic cerebrovascular disease.
