Polycomb group proteins Bmi-1 is the core subunits of the PRC1 complex,and also plays important roles in the regulation of neural development. This review introduces the construction of Bmi-1 and the recent study for ...Polycomb group proteins Bmi-1 is the core subunits of the PRC1 complex,and also plays important roles in the regulation of neural development. This review introduces the construction of Bmi-1 and the recent study for Bmi-1 in the nervous system development and tumor generation. The important roles of Bmi-1 for sustain of the neural stem cell proliferation,regulation mechanism of neural development and tumor generation are discussed.展开更多
The Sonic hedgehog (SHH) signaling pathway plays a pivotal role in neurogenesis and brain damage repair. Our previous work demonstrated that the SHH signaling pathway was involved in the neuroprotection of cortical ne...The Sonic hedgehog (SHH) signaling pathway plays a pivotal role in neurogenesis and brain damage repair. Our previous work demonstrated that the SHH signaling pathway was involved in the neuroprotection of cortical neurons against oxidative stress. The present study was aimed to further examine the underlying mechanism. The cortical neurons were obtained from one-day old Sprague-Dawley neonate rats. Hydrogen peroxide (H2O2, 100 μmol/L) was used to treat neurons for 24h to induce oxidative stress. Exogenous SHH (3μg/mL) was employed to activate the SHH pathway, and cyclopamine (20 μmol/L), a specific SHH signal inhibitor, to block SHH pathway. LY294002 (20 μmol/L) were used to pretreat the neurons 30 min before H2O2 treatment and selectively inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. The cell viability was measured by MTT and apoptosis rate by flow cytometry analysis. The expression of p38, p-p38, ERK, p-ERK, Akt, p-Akt, Bcl-2, and Bax in neurons was detected by immunoblotting. The results showed that as compared with H2O2 treatment, exogenous SHH could increase the expression of p-Akt by 20% and decrease the expression of p-ERK by 33%. SHH exerted no significant effect on p38 mitogen-activated protein kinase (p38 MAPK) pathway. Blockade of PI3K/Akt pathway by LY294002 decreased the cell viability by 17% and increased the cell apoptosis rate by 2-fold. LY294002 treatment could up-regulate the expression of the proapoptotic gene Bax by 12% and down-regulate the expression of the antiapoptotic gene Bcl-2 by 54%. In conclusion, SHH pathway may activate PI3K/Akt pathway and inhibit the activation of the ERK pathway in neurons under oxidative stress. The PI3K/Akt pathway plays a key role in the neuroprotection of SHH. SHH/PI3K/Bcl-2 pathway may be implicated in the protection of neurons against H2O2-induced apoptosis.展开更多
Mild encephalopathy/encephalitis with a reversible splenial(MERS) lesion is a clinic-radiological entity. The clinical features of MERS in neonates are still not systemically reported. This paper presents five cases o...Mild encephalopathy/encephalitis with a reversible splenial(MERS) lesion is a clinic-radiological entity. The clinical features of MERS in neonates are still not systemically reported. This paper presents five cases of MERS, and the up-to-date reviews of previously reported cases were collected and analyzed in the literature. Here we describe five cases clinically diagnosed with MERS. All of them were neonates and the average age was about 4 days. They were admitted for the common neurological symptoms such as hyperspasmia, poor reactivity and delirium. Auxiliary examinations during hospitalization also exhibited features in common. In this report, we reached following conclusions. Firstly, magnetic resonance imaging revealed solitary or comprehensive lesions in the splenium of corpus callosum, some of them extending to almost the whole corpus callosum. The lesions showed low intensity signal on T1-weighted images, homogeneously hyperintense signal on T2-weighted images, fluid-attenuated inversion recovery and diffusion-weighted images, and exhibited an obvious reduced diffusion on apparent diffusion coefficient map. Moreover, the lesions in the magnetic resonance imaging disappeared very quickly even prior to the clinical recovery. Secondly, all the cases depicted here suffered electrolyte disturbances especially hyponatremia which could be easily corrected. Lastly, all of the cases recovered quickly over one week to one month and majority of them exhibited signs of infections and normal electroencephalography.展开更多
The purpose of this study was to observe the expression of LINGO-1 after cerebral ischemia, investigate the effects of retinoic acid（RA） on the expression of LINGO-1 and GAP-43, and the number of synapses, and to em...The purpose of this study was to observe the expression of LINGO-1 after cerebral ischemia, investigate the effects of retinoic acid（RA） on the expression of LINGO-1 and GAP-43, and the number of synapses, and to emplore the repressive effect of LINGO-1 on neural regeneration after cerebral ischemia. The model of permanent focal cerebral ischemia was established by the modified suture method of middle cerebral artery occlusion（MCAO） in Sprague-Dawley（SD） rats. The expression of LINGO-1 was detected by Western blotting and that of GAP-43 by immunohistochemistry. The number of synapses was observed by transmission electron microscopy. The SD rats were divided into three groups： sham operation（sham） group, cerebral ischemia（CI） group and RA treatment（RA） group. The results showed that the expression level of LINGO-1 at 7th day after MCAO in sham, CI and RA groups was 0.266±0.019, 1.215±0.063 and 0.702±0.081, respectively（P〈0.01）. The number of Gap-43-positive nerve cells at 7th day after MCAO in sham, CI and RA group was 0, 59.08±1.76 and 76.20±3.12 per high power field, respectively（P〈0.05）. The number of synapses at 7th day after MCAO was 8.42±0.13, 1.74±0.37 and 5.39±0.26 per μm2, respectively（P〈0.05）. It is concluded that LINGO-1 expression is up-regulated after cerebral ischemia, and RA inhibits the expression of LINGO-1, promotes the expression of GAP-43 and increases the number of synapses. It suggests that LINGO-1 may be involved in the pathogenesis of cerebral ischemia, which may provide an experimenal basis for LINGO-1 antogonist, RA, for the treatment of cerebral ischemia.展开更多
Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asia...Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease（CAD） treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention（PCI）. The primary outcome of our interest was the recurrence of major adverse cardiovascular events（MACE） in those CAD patients. Firstly, we found that the distribution of reduced-function CYP2C19 allele varied between Westerners and Asians. Among Asians, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 42.5% and 10%, respectively. While among Westerners, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 25.5% and 2.4%, respectively. Secondly, the impact of CYP2C19 polymorphism on clinical outcomes of patients treated with clopidogrel varied with races. Among Asians, only 2 reduced-function CYP2C19 mutant allele carriers had the reduced effect of clopidogrel. And the reduced effect was significant only after the 30 th day of treatment. While among Westerners, both 1 and 2 reduced-function CYP2C19 allele carriers had the reduced effect, and it mainly occurred within the first 30 days. Thirdly, the safety of clopidogrel was almost the same among races. Reduced-function allele non-carriers had higher risk for total bleeding but did not have higher risk for major bleeding. It is suggested that CYP2C19 polymorphism affects the efficacy of clopidogrel differently among Westerners and Asians.展开更多
The effects of Sonic hedgehog(Shh) signaling pathway activation on S-type neuroblastoma(NB) cell lines and its role in NB tumorigenesis were investigated.Immunohistochemistry was used to detect the expression of Shh p...The effects of Sonic hedgehog(Shh) signaling pathway activation on S-type neuroblastoma(NB) cell lines and its role in NB tumorigenesis were investigated.Immunohistochemistry was used to detect the expression of Shh pathway components— Patched1(PTCH1) and Gli1 in 40 human primary NB samples.Western blotting and RT-PCR were used to examine the protein expression and mRNA levels of PTCH1 and Gli1 in three kinds of S-type NB cell lines(SK-N-AS,SK-N-SH and SHEP1),respectively.Exogenous Shh was administrated to activate Shh signaling pathway while cyclopamine was used as a selective antagonist of Shh pathway.S-type NB cell lines were treated with different concentrations of Shh or/and cyclopamine for different durations.Cell viability was measured by using MTT method.Apoptosis rate and cell cycle were assayed by flow cytometry.The xenograft experiments were used to evaluate the role of Shh pathway in tumor growth in immunodeficient mice.High-level expression of PTCH1 and Gli1 was detected in both NB samples and S-type NB cell lines.Cyclopamine decreased the survival rate of the three cell lines while Shh increased it,and the inhibition effects of cyclopamine could be partially reversed by shh pre-treatment.Cyclopamine induced the cell apoptosis and the cell cycle arrest in G0/G1 phase,while Shh induced the reverse effects and could partially prevent effects of cyclopamine.Cyclopamine could also inhibit the growth of NB in vivo.Our studies revealed that activation of the Shh pathway is important for survival and proliferation of S-type NB cells in vivo and in vitro through affecting cell apoptosis and cell cycle,suggesting a new therapeutic approach to NB.展开更多
文摘Polycomb group proteins Bmi-1 is the core subunits of the PRC1 complex,and also plays important roles in the regulation of neural development. This review introduces the construction of Bmi-1 and the recent study for Bmi-1 in the nervous system development and tumor generation. The important roles of Bmi-1 for sustain of the neural stem cell proliferation,regulation mechanism of neural development and tumor generation are discussed.
基金supported by a grant from the National Natural Science Foundation of China(No.81070938)
文摘The Sonic hedgehog (SHH) signaling pathway plays a pivotal role in neurogenesis and brain damage repair. Our previous work demonstrated that the SHH signaling pathway was involved in the neuroprotection of cortical neurons against oxidative stress. The present study was aimed to further examine the underlying mechanism. The cortical neurons were obtained from one-day old Sprague-Dawley neonate rats. Hydrogen peroxide (H2O2, 100 μmol/L) was used to treat neurons for 24h to induce oxidative stress. Exogenous SHH (3μg/mL) was employed to activate the SHH pathway, and cyclopamine (20 μmol/L), a specific SHH signal inhibitor, to block SHH pathway. LY294002 (20 μmol/L) were used to pretreat the neurons 30 min before H2O2 treatment and selectively inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. The cell viability was measured by MTT and apoptosis rate by flow cytometry analysis. The expression of p38, p-p38, ERK, p-ERK, Akt, p-Akt, Bcl-2, and Bax in neurons was detected by immunoblotting. The results showed that as compared with H2O2 treatment, exogenous SHH could increase the expression of p-Akt by 20% and decrease the expression of p-ERK by 33%. SHH exerted no significant effect on p38 mitogen-activated protein kinase (p38 MAPK) pathway. Blockade of PI3K/Akt pathway by LY294002 decreased the cell viability by 17% and increased the cell apoptosis rate by 2-fold. LY294002 treatment could up-regulate the expression of the proapoptotic gene Bax by 12% and down-regulate the expression of the antiapoptotic gene Bcl-2 by 54%. In conclusion, SHH pathway may activate PI3K/Akt pathway and inhibit the activation of the ERK pathway in neurons under oxidative stress. The PI3K/Akt pathway plays a key role in the neuroprotection of SHH. SHH/PI3K/Bcl-2 pathway may be implicated in the protection of neurons against H2O2-induced apoptosis.
基金supported by Wuhan Clinical Medical Research Center for Children’s Neural Disease(No.2014-160)
文摘Mild encephalopathy/encephalitis with a reversible splenial(MERS) lesion is a clinic-radiological entity. The clinical features of MERS in neonates are still not systemically reported. This paper presents five cases of MERS, and the up-to-date reviews of previously reported cases were collected and analyzed in the literature. Here we describe five cases clinically diagnosed with MERS. All of them were neonates and the average age was about 4 days. They were admitted for the common neurological symptoms such as hyperspasmia, poor reactivity and delirium. Auxiliary examinations during hospitalization also exhibited features in common. In this report, we reached following conclusions. Firstly, magnetic resonance imaging revealed solitary or comprehensive lesions in the splenium of corpus callosum, some of them extending to almost the whole corpus callosum. The lesions showed low intensity signal on T1-weighted images, homogeneously hyperintense signal on T2-weighted images, fluid-attenuated inversion recovery and diffusion-weighted images, and exhibited an obvious reduced diffusion on apparent diffusion coefficient map. Moreover, the lesions in the magnetic resonance imaging disappeared very quickly even prior to the clinical recovery. Secondly, all the cases depicted here suffered electrolyte disturbances especially hyponatremia which could be easily corrected. Lastly, all of the cases recovered quickly over one week to one month and majority of them exhibited signs of infections and normal electroencephalography.
基金supported by grants from the Key Programs for Science and Technology Development of Hubei Province,China(No.2007AA301B34-2)the Openning Fund for Key Laboratory of Molecular Imaging of Hubei Province,China(No.2008-74)
文摘The purpose of this study was to observe the expression of LINGO-1 after cerebral ischemia, investigate the effects of retinoic acid（RA） on the expression of LINGO-1 and GAP-43, and the number of synapses, and to emplore the repressive effect of LINGO-1 on neural regeneration after cerebral ischemia. The model of permanent focal cerebral ischemia was established by the modified suture method of middle cerebral artery occlusion（MCAO） in Sprague-Dawley（SD） rats. The expression of LINGO-1 was detected by Western blotting and that of GAP-43 by immunohistochemistry. The number of synapses was observed by transmission electron microscopy. The SD rats were divided into three groups： sham operation（sham） group, cerebral ischemia（CI） group and RA treatment（RA） group. The results showed that the expression level of LINGO-1 at 7th day after MCAO in sham, CI and RA groups was 0.266±0.019, 1.215±0.063 and 0.702±0.081, respectively（P〈0.01）. The number of Gap-43-positive nerve cells at 7th day after MCAO in sham, CI and RA group was 0, 59.08±1.76 and 76.20±3.12 per high power field, respectively（P〈0.05）. The number of synapses at 7th day after MCAO was 8.42±0.13, 1.74±0.37 and 5.39±0.26 per μm2, respectively（P〈0.05）. It is concluded that LINGO-1 expression is up-regulated after cerebral ischemia, and RA inhibits the expression of LINGO-1, promotes the expression of GAP-43 and increases the number of synapses. It suggests that LINGO-1 may be involved in the pathogenesis of cerebral ischemia, which may provide an experimenal basis for LINGO-1 antogonist, RA, for the treatment of cerebral ischemia.
基金supported by grants from National Natural Science Foundation of China(Nos.81371311 and 81101905)New Century Excellent Talents in University of China(No.NCET-10-0406)
文摘Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease（CAD） treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention（PCI）. The primary outcome of our interest was the recurrence of major adverse cardiovascular events（MACE） in those CAD patients. Firstly, we found that the distribution of reduced-function CYP2C19 allele varied between Westerners and Asians. Among Asians, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 42.5% and 10%, respectively. While among Westerners, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 25.5% and 2.4%, respectively. Secondly, the impact of CYP2C19 polymorphism on clinical outcomes of patients treated with clopidogrel varied with races. Among Asians, only 2 reduced-function CYP2C19 mutant allele carriers had the reduced effect of clopidogrel. And the reduced effect was significant only after the 30 th day of treatment. While among Westerners, both 1 and 2 reduced-function CYP2C19 allele carriers had the reduced effect, and it mainly occurred within the first 30 days. Thirdly, the safety of clopidogrel was almost the same among races. Reduced-function allele non-carriers had higher risk for total bleeding but did not have higher risk for major bleeding. It is suggested that CYP2C19 polymorphism affects the efficacy of clopidogrel differently among Westerners and Asians.
基金supported by a grant from the National Natural Sciences Foundation of China (No.30600189)
文摘The effects of Sonic hedgehog(Shh) signaling pathway activation on S-type neuroblastoma(NB) cell lines and its role in NB tumorigenesis were investigated.Immunohistochemistry was used to detect the expression of Shh pathway components— Patched1(PTCH1) and Gli1 in 40 human primary NB samples.Western blotting and RT-PCR were used to examine the protein expression and mRNA levels of PTCH1 and Gli1 in three kinds of S-type NB cell lines(SK-N-AS,SK-N-SH and SHEP1),respectively.Exogenous Shh was administrated to activate Shh signaling pathway while cyclopamine was used as a selective antagonist of Shh pathway.S-type NB cell lines were treated with different concentrations of Shh or/and cyclopamine for different durations.Cell viability was measured by using MTT method.Apoptosis rate and cell cycle were assayed by flow cytometry.The xenograft experiments were used to evaluate the role of Shh pathway in tumor growth in immunodeficient mice.High-level expression of PTCH1 and Gli1 was detected in both NB samples and S-type NB cell lines.Cyclopamine decreased the survival rate of the three cell lines while Shh increased it,and the inhibition effects of cyclopamine could be partially reversed by shh pre-treatment.Cyclopamine induced the cell apoptosis and the cell cycle arrest in G0/G1 phase,while Shh induced the reverse effects and could partially prevent effects of cyclopamine.Cyclopamine could also inhibit the growth of NB in vivo.Our studies revealed that activation of the Shh pathway is important for survival and proliferation of S-type NB cells in vivo and in vitro through affecting cell apoptosis and cell cycle,suggesting a new therapeutic approach to NB.
