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BACKGROUND:Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic,but only a few patients benefit from vascular recanalization in time,so it is urgent to explore new and effective therapy.As one of the critical pathological changes of ischemic stroke,the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke. OBJECTIVE:To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke,as well as the potential therapeutic targets,to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively,and novel strategies for promoting post-stroke rehabilitation. METHODS:The relevant articles published in CNKI,PubMed and Web of Science databases from 2010 to 2022 were retrieved.The search terms were"Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis"in Chinese and English.Finally,78 articles were included after screening and summarized. RESULTS AND CONCLUSION:(1)Astrocytes play an important role in the maintenance of central nervous system homeostasis.After ischemic stroke,astrocytes change from a resting state to an active state.According to the different severities of cerebral ischemic injury,astrocyte activation changes dynamically from swelling and proliferation to glial scar formation.(2)Mature astrocytes are stimulated to restart the cell cycle,then proliferate and migrate to lesions,which is the main source of the glial scar.Neural stem cells in the subventricular zone,neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes.Endothelin-1,aquaporin 4,ciliary neurotrophic factor and connexins are involved in this process.In addition,chondroitin sulfate proteoglycan,as the main component of the extracellular matrix,forms the dense glial scar barrier with proliferated astrocytes,which hinders the polarization and extension of axons.(3)Activation or inhibition of crucial signal molecules involved in astrocyte activation,proliferation,migration and pro-inflammation functions regulate the glial scar formation.Transforming growth factor beta 1/Smad and Janus kinase/signal transducer and activator of transcription 3 are classical pathways related to astrogliosis,while receptor-interacting protein 1 kinase and glycogen synthase kinase 3β are significant molecules regulating the inflammatory response.However,there are relatively few studies on Smad ubiquitination regulatory factor 2 and Interleukin-17 and their downstream signaling pathways in glial scar formation,which are worthy of further exploration.(4)Drugs targeting astrogliosis-related signaling pathways,cell proliferation regulatory proteins and inflammatory factors effectively inhibit the formation of glial scar after cerebral ischemic stroke.Among them,the role of commonly used clinical drugs such as melatonin and valproic acid in regulating glial scar formation has been verified,which makes it possible to use drugs that inhibit glial scar formation to promote the recovery of neurological function in patients with stroke.(5)Considering the protective effects of glial scar in the acute phase,how to choose the appropriate intervention chance of drugs to maintain the protective effect of the glial scar while promoting nerve regeneration and repair in the local microenvironment is the direction of future efforts.
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Objective To explore the effect of inhibiting Akt phosphorylation on tumor necrosis factor related apoptosis inducing ligand (TRAIL)-induced apoptosis of human non-small cell lung cancer (NSCLC) H1299 cells with wild type EGFR and KRAS.Methods The TRAIL-induced apoptosis was examined by the Annexin V-FITC/PI.The expressions of TRAIL-activated Akt phosphorylation and p-Akt were measured by Western blot.After cells were treated with LY294002, an inhibitor of PI3K-Akt pathway, Annexin V-FITC/PI and Western blot were used to analyze the alteration of TRAIL-induced apoptosis and Akt phosphorylation, respectively.Results H1299 cells were not sensitive to TRAIL-induced apoptosis.When TRAIL concentration was 100 ng/ml, the apoptosis rate of the test group was significantly higher than that of the control group [(15.06±1.29) ％ vs (3.56±0.50) ％, t =66.953, P =0.000].When TRAIL concentration was 500 ng/ml, the difference was not statistically significant compared with apoptosis rate of 100 ng/ml TRAIL group [(18.65±2.09) ％ vs (15.06±1.29) ％, t =2.423, P =0.136].The expression level of Akt phosphorylation in H1299 cells was increased by TRAIL in a time-dependent way.When cells were pretreated with LY294002, TRAIL-induced Akt phosphorylation was suppressed to baseline level.At the same time, the apoptosis rate in LY294002-treated group was significantly higher than that in TRAIL group [(41.65±4.62) ％ vs (15.82±0.61) ％, t =39.028, P =0.001].Conclusions TRAIL-induced Akt phosphorylation can antagonize TRAIL-induced apoptosis.Inhibition of Akt phosphorylation can significantly enhance the sensitivity of NSCLC H1299 cells with wild type EGFR and KRAS to TRAIL-induced apoptosis.
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Objective To investigate the clinical value of strain ratio in differential diagnosis of thyroid tumors,compared with the evaluation based on elastography scores.Methods Elastography examinations were performed in 67 patients with 92 thyroid tumors.Ultrasonic elastograms were evaluated according to the four- and five-score system respectively.Strain ratio of the tumor and the surrounding tissue was also calculated.Clinical value of the three evaluations was compared with pathological findings as the reference standard.Results The area under the curve:0.885 for the four-score,0.904 for the five-score,0.961 for the strain ratio.When a cutoff point of 3 was used,four-score and five-score showed a sensitivity of 78.0%,a specificity of 86.3%,an accuracy of 82.6% and a sensitivity of 80.5%,a specificity of 88.2%,an accuracy of 84.8%,respectively.When a cutoff point of 3.57 was introduced,the strain ratio had 92.7% sensitivity,92.2% specificity,92.4% accuracy.Conclusions Strain ratio was more helpful in diagnostic performance of thyroid tumors as a new semi-quantitative method than elastography scores.
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Objective To summarize the characters of the elastograms of different pathological nodules, and to observe the value of elastography in differentiating benign from malignant thyroid solid nodules. Methods One hundred and sixteen patients with thyroid nodules were enrolled in the study and 122 nodules were detected in total. All of them were examined by elastography and conventional ultrasound. Five sonographers were invited to evaluate the nodules double blinded basing on the images and the four-point system proposed by Fukunari. The interobserver agreement was evaluated by Kappa coefficient. Diagnostic performances of the five readers were compared by the ROC curves. Distributions of elastography scores of different pathological nodules were compared by one-way ANOVA. Results Interobserver agreements on scoring the nodules were moderate. Mean value of benign nodules was obvious lower than that of the malignant ones. The mean score of nodular goiters was 2.67 ± 0.89, range from 1 to 3. Most of the adenomas got score of 2, but the score of thyroiditis was quite high. No significant differences were found between the comparison of thyroiditis and thyroid cancers. Areas under the ROC curve (AUC) of the five readers were 0.82,0.81,0.79,0.73 and 0.83 respectively. When 3.5 was choosen as the cut-off point, the sensitivity of elastography was 82.4%, and specificity was 71.6%. Conclusions Elastography was really a useful technique for it can provide a new index for the differential diagnosis of thyroid nodules. However, the 4-point score system is not comprehensive enough.
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<p><b>OBJECTIVE</b>To study effects of polysaccharide of Radix Ranunculi Ternati (PRT) on immunological function and anti-oxidation activity of mouse.</p><p><b>METHOD</b>Cell proliferations of splenocyte, thymocyte and peritoneal macrophage were measured by MTT colorimetry. The phagocytic function of peritoneal macrophage was measured by neutral red colorimetric method. The disoxidation power of PRT was measured by Prussian blue method. The clearing effect of PRT on hydroxyl radical was measured by salicylic acid capture method. The clearing effect of PRT on superoxide anion free radical was measured by pyrogallol auto oxidation method.</p><p><b>RESULT</b>PRT among 25-400 mg x L(-1) could enhance thymocytes and spleen lymphocyte proliferation and macrophage phagocytosis. PRT(200 mg x L(-1)) has the strongest macrophage proliferation. PRT in different concentration has shown some disoxidation effects. PRT in 8 g x L(-1) has nearly the same ability of clearing x OH by Vit C with the same concentration. The clearance rate of PRT on O2*- is 95.39%.</p><p><b>CONCLUSION</b>PRT can enhance the cell proliferation capability of thymocytes, spleen lymphocytes and peritoneal macrophages. PRT can enhance macrophage phagocytosis in a dose-response relationship. PRT has saome disoxidation power and strong ability of clearing x OH and O2*-.</p>