新世纪大学生的特点在医学教育中的应用

高等教育正从以教授者为中心向以学习者为中心转化,在此过程中要充分考虑新世纪大学生的特点。如今医科院校的大学生不仅具备新世纪大学生的个性特点与时代特点,而且同时具备医科院校学生独具的成绩优异生集体的特点。本文从新世纪大学生的个性特点、时代特点、医科院校学生特点等三方面入手,对新世纪医科院校大学生的特点进行了分析研究,并以此为基础对医科院校在进行教育教学改革时需要关注的内容提出了启示。

医学药理学教考分离实践对教学的指导意义

教考分离是高等教育改革的重要一环,本文通过建立药理学标准化试题库,并在学生中进行了与教考合一制度的对比研究,初步证实其评价结果更客观、真实,是更科学严谨的评价体系。

Small-molecule inhibitor of smoothend suppress neuroinflammation through hedgehog signaling independent mechanisms

OBJECTIVE Microglial activation mediated neuroinflammation plays an important role in the progression of neurodegerative diseases.The purpose of this study was to investigate the effect of small-molecule inhibitors of smoothend(Smo) on microglial activation mediate neuroinflammation.METHODS To search for the novel anti-neuroinflammatory agents,the BV-2 cel-based nitric oxide(NO) assay was used to screen a series of small-molecule inhibitors of Smo.The production of NO and cell viability were detected by Griess and MTT assay respectively.The expression of inflammatory factors were evaluated by Real-time quantitative PCR or Western blotting or ELISA assay,and activation of signal molecules were detected by Western blotting.The dopaminergic neuronal cell apoptosis were measured by flow cytometry.The stereotaxic injection of LPS into the mice Substantia Nigra(SN) were employed to establish animal model of neuroinflammation and immunofluorescence staining on brain slices sections were used to verify microglial activation and dopaminergic cell loss.RESULTS To search for the compounds that inhibit microglial activation,we have screened a series of Smo inhibitors(0.01-40 μmol·L^(-1)) for the activity to inhibit NO production in BV-2 microglia cells.Among the Smo inhibitors tested,Hh-079 strongly inhibited LPS-induced microglial NO production without affecting the cell viability.Hh-079 significantly inhibited the expression of proinflammatory factors in LPSstimulated BV-2 microglial cells.Hh-079 inhibited phosphorylation of IKKα/β,phosphorylation and degradation of IκBα,phosphorylation of P65 subunit of NF-κB and NF-κB transcriptional activity in LPS-stimulated BV-2 microglial cells.Hh-079 reduced cytotoxicity of conditioned media of activated microglia toward HT-22 neuroblastoma cells in a co-culture system.Mechanistic studies demonstrated that among the Shh-Ptch-Gli pathway,microglia cells did not express detectable levels of Shh,Smo and Gli.Furthermore,neither Smo inhibitor cyclopamine no Gli inhibitor GANT61 exhibited inhibitory properties on proinflammatory genes expression in LPS activated microglia cells.In addition,co-treatment of recombinant Shh or Smo agonist SAG did not block inhibitory effects of Hh-079 on proinflammatory gene expression in LPS activated microglia cells.In vivo study demonstrated that pretreatment of Hh-079(25 and 50 mg·kg-1) significantly reduced TH-positive cells loss and microglia cells activation in the LPS induced neuroinflammation mouse model.CONCLUSION Smo inhibitor Hh-079 suppress neuroinflammation through hedgehog signaling independent mechanisms.

Inhibition of glycolysis mitigate microglial-activation mediated neuroinflammation in vitro and in vivo

OBJECTIVE Microglial activation-mediated neuroinflammation plays an important pathological basis in the progression of many neurodegenerative diseases.Activated microglia cells show a metabolic shift from oxidative phos⁃phorylation to aerobic glycolysis.However,the molecular mechanism underlying the role of glycolysis in microglial activation and progres⁃sion of neuroinflammatory diseases have not yet been fully understood.METHODS The anti-inflammatory effects and its underlying mecha⁃nisms of glycolytic inhibition in vitro were exam⁃ined in lipopolysaccharide(LPS)activated BV-2 microglial cells or primary microglial cells by enzyme-linked immunosorbent assay(ELISA),quantitative reverse transcriptase polymerase chain reaction(RT-PCR),Western blotting,immunoprecipitation,Flow cytometry and nuclear factor kappa B(NF-κB)luciferase reporter assays.In vivo,the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-or LPS-induced Par⁃kinson disease(PD)models were constructed to explored the anti-inflammatory and neuropro⁃tective effects of glycolytic inhibitor.RESULTS Inhibition of glycolysis by specific inhibitors[2-DG and 3-bromopyruvic acid(3-BPA)],knockdown of glucose transporter type 1(Glut-1)or hexoki⁃nase(HK)Ⅱabolished LPS-induced expres⁃sion of proinflammatory genes in microglia cells.Mechanistic studies demonstrated that glyco⁃lytic inhibitors significantly inhibited LPS-induced mTOR phosphorylation,IKKβphosphorylation,IκB phosphorylation,IκB degradation,nuclear translocation of P65 and NF-κB luciferase activity.Furthermore,LPS-induced P65 acetyla⁃tion on lysine 310,which is mediated by NAD-dependent protein deacetylase sirtuin-1 and is critical for NF-kB activation,were inhibited by glycolytic inhibitors.A coculture study revealed that 2-DG reduced the cytotoxicity of activated microglia toward MES23.5 dopaminergic neuron cells with no direct protective effect.In vivo,2-DG significantly ameliorated MPTP or LPS induced DA neuron loss and glial cell activation.CONCLUSION Glycolysis is actively involved in microglial activation.Inhibition of glycolysis can ameliorate microglial activation-related neuroinflammatory diseases.