ABSTRACT
We have previously reported that Cystatin C (CysC) is a pivotal mediator in the neuroprotection induced by hyperbaric oxygen (HBO) preconditioning; however, the underlying mechanism and how CysC changes after stroke are not clear. In the present study, we demonstrated that CysC expression was elevated as early as 3 h after reperfusion, and this was further enhanced by HBO preconditioning. Concurrently, LC3-II and Beclin-1, two positive-markers for autophagy induction, exhibited increases similar to CysC, while knockdown of CysC blocked these elevations. As a marker of autophagy inhibition, p62 was downregulated by HBO preconditioning and this was blocked by CysC knockdown. Besides, the beneficial effects of preserving lysosomal membrane integrity and enhancing autolysosome formation induced by HBO preconditioning were abolished in CysC rats. Furthermore, we demonstrated that exogenous CysC reduced the neurological deficits and infarct volume after brain ischemic injury, while 3-methyladenine partially reversed this neuroprotection. In the present study, we showed that CysC is biochemically and morphologically essential for promoting autophagic flux, and highlighted the translational potential of HBO preconditioning and CysC for stroke treatment.
Subject(s)
Animals , Male , Autophagy , Physiology , Beclin-1 , Metabolism , Brain , Metabolism , Pathology , Brain Ischemia , Metabolism , Pathology , Therapeutics , Cystatin C , Genetics , Metabolism , Disease Models, Animal , Gene Expression , Gene Knockdown Techniques , Hyperbaric Oxygenation , Lysosomes , Metabolism , Pathology , Microtubule-Associated Proteins , Metabolism , Neurons , Metabolism , Pathology , Neuroprotection , Physiology , Oxygen , Therapeutic Uses , Random Allocation , Rats, Sprague-Dawley , Rats, Transgenic , Reperfusion Injury , Metabolism , Pathology , TherapeuticsABSTRACT
Objective To evaluate the effect of TanshinonneⅡA preconditioning on nuclear factor kappa B ( NF-κB ) signaling pathway in N9 cells subjected to oxygen-glucose deprivation and restoration ( OGD∕R) . Methods N9 cells cultured in vitro were divided into 4 groups ( n=16 each) by using a ran-dom number table method: control group ( C group) , OGD∕R group, vehicle group ( V group) and Tanshi-none ⅡA preconditioning group ( TP group) . N9 cells were subjected to O2-glucose deprivation for 4 h fol-lowed by restoration of O2-glucose supply for 24 h to establish the OGD∕R model. Group C receive no treat-ment. In group TP, N9 cells were cultured in medium containing Tanshinone ⅡA ( final concentration 5 mg∕L) for 24 h before the model was established. Dimethyl sulfoxide was added to the culture medium in group V. At the 24 h of reoxygenation, the level of lactate dehydrogenase ( LDH) and nitric oxide ( NO) in culture medium was detected by spectrophotometry, cell apoptosis was assessed by using TUNEL, and the expression of NF-κB in nucleus was detected by Western blot. The apoptosis rate was calculated. Results Compared with group C, the levels of LDH, IL-β, TNF-α and NO in culture medium and apoptosis rate were significantly increased, and the expression of NF-κB in nucleus was up-regulated in OGD∕R, V and TP groups ( P<0. 05) . Compared with group OGD∕R, the levels of LDH, IL-β, TNF-αand NO in culture me-dium and apoptosis rate were significantly decreased, and the expression of NF-κB in nucleus was down-reg-ulated in group TP ( P<0. 05) , and no significant change was found in the parameters mentioned above in group V ( P>0. 05 ) . Conclusion The mechanism by which Tanshinonne ⅡA preconditioning reduces OGD∕R injury to N9 cells is related to inhibiting NF-κB signaling pathway.
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Objective To study the nation-wide cooperation network of bio-genomics for major disease clinical samples and the development of bio-genomics database.Methods The clinical phenotypes and genomics data of disease cohort were investigated,the cooperation network of bio-genomics for major disease clinical samples and the development of bio-genomics database were analyzed,the key technologies for different tasks were studied.Results The key contents and technologies involving the development of bio-genomics database for major disease clinical samples were proposed and how to solve the following problems was pointed out,including the integration of phenotypes and new technologies in the genomics field,multi-granular and multi-modular retrieval,and computing service.Conclusion It is of great importance to establish the standards for data cooperation process and data security management,to research and develop platform for cooperation network and database,to study the service model for the integration of big data in precision medicine based on data cooperation network.
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Objective To establish a stem cell life-cycle management information system to realize collection,storage,inquiry,processing and statistical analysis of the stem cell and to provide information for the research on stem cell translation medicine.Methods The functional modules of the system were determined based on the analyses on the requirements of stem cell bank management and its operational flow.The system design was explored from the aspects of technical framework,safety control and fuzzy query.Results The system was gifted with a technical architecture and anallocation scheme based on Spring MVC mode,which proved its efficiency by the trial.Conclusion Stem cell resource library can be used as an important supplement to the clinical sample life-group database,providing data and technical basis support for large-scale clinical samples to transform,integrate,manage and share large data resources.
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Objective To explore the solution for regional population health information platform based on the involvement of internet plus and big data.MethodsThe objective and contents of the platform were discussed,and its logic structure and deployment architecture were designed.The functions of a platform-based application system and two information integration platforms were described.The key technical links of the system were demonstrated.Results The solution for regional population health information platform based on internet plus completed population health information service system,and laid a foundation for the application of medical big data.Conclusion The solution contributes to the inter-connection and communication between medical fields in some region,promotes healthcare informatizatoin platform and is thus worthy applying practically.
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Medical big data, an important strategic source of basic data for a country, will be applied in precision clinical diagnosis and treatment, decision-making support, disease monitoring, early warning and management, and public health service. The application of medical big data technology in our country is to be improved at pres-ent. How to realize the smooth transition of traditional medical data to a big data system and the added value of data by data mining and analyzing is an important problem needing to be solved immediately. The key functions, inclu-ding the general frame work and data center frame work of medical big data application information system, were thus planned and designed in this paper by constructing the regional application technology and engineering labora-tory for medical big data.
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The assessment method for pharmacology courses in top-up program of Yanjing medical college was reformed supported by the principal foundation from China capital medical university.The reform specified the assessment content and examination syllabus,formed the multilayer assessing methods and assessing modes and assessed objectively through questionnaires and investigations.The results showed that the students were satisfied with the assessment mode,degree of standardization and the implementation effect. Pharmacology teaching was effectively assessed by the new method and students′ comprehensive ability was improved.
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Objective To investigate the role of N-myc downstream regulated genes 2 (NDRG2) in attenuation of focal cerebral ischemic-reperfusin injury by sevoflurane preconditioning in rats.Methods Forty-eight healthy male SD rats weighing 280-320 g were randomly divided into 3 groups ( n =16 each):sham operation group (group S),ischemia-reperfusion injury group (group I/R) and sevoflurane preconditioning group (group Sev).Focal cerebral ischemia-reperfusion injury was induced by right middle cerebral artery occlusion (MCAO)for 120 min followed by 24 h reperfusion.In group Sev,2.0％ sevoflurane was inhaled 1 h once a day for 5 consecutive days at 24 h before MCAO.The neurologic function was evaluated at 24 h of reperfusion and than the rats were sacrificed,and the brain was removed for determination of infarct volume percentage,NDRG2 and activated Caspase-3 expression in ischemic penumbra by Western Blot and NDRG2 expression and location by immunohistochemistry.Results The infarct volume percentage,NDRG2 and activated Caspase-3 expression were higher,and neurologic function score was lower in groups I/R and Sev then in group S( P ＜ 0.05).The infarct volume percentage,NDRG2 and activated Caspase-3 expression were lower,and neurologic function score was higher in group Sev then in group I/R ( P ＜ 0.05).The intranuclear NDRG2 positive staining was decreased in group Sev than in group I/R.Conclusion Sevoflurane preconditioning can reduce focal cerebral ischemia-reperfusion injury by inhibiting the expression and activity of NDRG2 and apoptosis in rats.
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In the process of development and exploitation of information resources for the medicalsector, business synergy and information exchange/sharing become more and more frequent across departments. How to effectively sort massive information resources involved in the departments has become a bottleneck. The author proposed a complete set of thoughts to sort relations among businesses, from the aspects of functionality layer, service layer, and data layer, in view of the business problems to resolve by the departments.
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Objective:To study the application and clinical significance of autotransfusion hemodilution inlaryngectomy. Method:Autotransfusion hemodilution was adopted in 30 patients with Ⅲ or Ⅳ stage laryngealcarcinoma during operation as the experimental group, and the blood transfusion only was adopted in the patientswith excessively blood loss. The other 30 patients with the same stages of disease and the same kinds ofoperation were performed as the control group, without autotransfusion hemodilution and the blood transfusionwas adopted if necessary. Result: Blood transfusion was necessary to be performed only in 8 patients of theexperimental group, on the contrary,it was necessary in 19 of 30 patients of the control group (P＜0.01).There were no complications during the operations , and the postoperative complications were no significance (P＞0. 05) between two groups. Conclusion:The application of autotransfusion hemodilution may be of help to aplenty of patients with laryngeal carcinoma in advanced stage to keep off the blood transfusion duringlaryngectomy.