Liu X.-J.,Peking University |
Wu W.-T.,Peking University |
Wu W.-H.,Peking University |
Yin F.,The Navy General Hospital of PLA China |
And 11 more authors.
CNS Neuroscience and Therapeutics | Year: 2013
Aims: To study the contribution of epidermal growth factor receptor variant III (EGFRvIII) to glioblastoma multiforme (GBM) stemness and gefitinib resistance. Methods: CD133+ and CD133- cells were separated from EGFRvIII+ clinical specimens of three patients with newly diagnosed GBM. Then, RT-PCR was performed to evaluate EGFRvIII and EGFR expression in CD133+ and CD133- cells. The tumorigenicity and stemness of CD133+ cells was verified by intracranial implantation of 5 × 103 cells into immunodeficient NOD/SCID mice. Finally, cells were evaluated for their sensitivity to EGFR tyrosine kinase inhibition by gefitinib. Results: RT-PCR results showed that the sorted CD133+ cells expressed EGFRvIII exclusively, while the CD133- cells expressed both EGFRvIII and EGFR. At 6-8 weeks postimplantation, CD133+/EGFRvIII+/EGFR- cells formed intracranial tumors. Cell counting kit-8 results showed that the IC50 values of the three isolated EGFRvIII+ cell lines treated with gefitinib were 14.44, 16.00, and 14.66 μM, respectively, whereas the IC50 value of an isolated EGFRvIII- cell line was 8.57 μM. Conclusions: EGFRvIII contributes to the stemness of cancer stem cells through coexpression with CD133 in GBMs. Furthermore, CD133+/EGFRvIII+/EGFR- cells have the ability to initiate tumor formation and may contribute to gefitinib resistance. © 2013 John Wiley & Sons Ltd.
Cui X.,Capital Medical University |
Xu Z.,Peking Union Medical College |
Zhao Z.,Capital Medical University |
Sui D.,Capital Medical University |
And 7 more authors.
International Journal of Biological Sciences | Year: 2013
Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability and unpredictable clinical behavior. GBM is marked by an extremely poor prognosis with median overall survival of 12~14 months. In this study, we detected the CD137L-expressing cells and IL-17-expressing cells in tumor tissues resected from patients with GBM. Expression of CD137L and IL-17 were assessed by immunohistochemistry, and the prognostic value of CD137L and IL-17 expression within the tumor tissues were assessed by Cox regression and Kaplan-Meier analysis. Immunohistochemical detection showed that positive cells of CD137L and IL-17 in glioblastoma tissue samples were 46.3% (19/ 41) and 73.2% (30/41) respectively. Expression of CD137L was not correlated with overall survival of GBM patients (P=0.594), while significantly longer survival rate was seen in patients with high expression of IL-17, compared to those with low expression of IL-17 (P=0.007). In addition, we also found that IL-17 expression was significantly correlated with Progression-free survival (PFS) (P=0.016) and death rate (P=0.01). Furthermore, multivariate Cox proportional hazard analyses revealed that IL-17 (P=0.018) and PFS (P=0.028) were independent factors affecting the overall survival probability. Kaplan-Meier analysis showed that PFS of high expression of IL-17 group were significantly longer (P=0.004) than low expression group with GBM. It is concluded that high levels of IL-17 expression in the tumor tissues may be a good prognostic marker for patients with GBM. © Ivyspring International Publisher.
Jiao J.,China National Institute of Biological Sciences |
Jiao J.,Beijing Normal University |
Yang Y.,Guangzhou Medical College |
Yang Y.,China National Institute of Biological Sciences |
And 9 more authors.
Human Molecular Genetics | Year: 2013
Severe myoclonic epilepsy of infancy (SMEI, also known as Dravet syndrome) and genetic epilepsy with febrile seizures plus (mild febrile seizures) can both arise due to mutations of SCN1A, the gene encoding alpha 1 poreforming subunit of the Nav1.1 voltage-gated sodium channel. Owing to the inaccessibility of patient brain neurons, the precise mechanism of mild febrile seizures and SMEI remains elusive, and there is no effective pharmacotherapy. Induced pluripotent stem cells (iPSCs) and induced neurons (iNs) have been successfully generated from patients and applied for modeling various neuronal diseases. In this study, we established iPSC lines from one SMEI patient and one mild febrile seizures patient, respectively. Functional glutamatergic neurons were subsequently differentiated from these iPSCs. Electrophysiological analysis of patient iPSCderived glutamatergic neurons revealed a hyperexcitable state of enlarged and persistent sodium channel activation, more intensive evoked action potentials and typical epileptic spontaneous action potentials. In consistent with the severity of the symptoms, the hyperexcitability of the neurons derived from SMEI patient was more serious than that of mild febrile seizures patient. Furthermore, the hyperexcitability of the neurons can be alleviated by treatment with phenytoin, a conventional antiepileptic drug. In parallel, iNs were directly converted from patient fibroblasts which also showed a delayed inactivation of sodium channels. Our results demonstrate that both iPSC-derived neurons and iNs from mild febrile seizures and SMEI patients exhibited a hyperexcitable state. More importantly, patient iPSC-derived neurons can recapitulate the neuronal pathophysiology and respond to drug treatment, indicating that these neurons can be potentially used for screening appropriate drugs for personalized therapies. © The Author 2013. Published by Oxford University Press. All rights reserved.
PubMed | The affiliated Bayi Brain Hospital and Southern Medical University
Type: Journal Article | Journal: Cellular and molecular neurobiology | Year: 2016
Here, we have investigated the synergistic effect of quercetin administration and transplantation of human umbilical cord mesenchymal stromal cells (HUMSCs) following middle cerebral artery occlusion in rat. Combining quercetin treatment with delayed transplantation of HUMSCs after local cerebral ischemia significantly (i) improved neurological functional recovery; (ii) reduced proinflammatory cytokines (interleukin(IL)-1 and IL-6), increased anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor-1), and reduced ED-1 positive areas; (iii) inhibited cell apoptosis (caspase-3 expression); and (iv) improved the survival rate of HUMSCs in the injury site. Altogether, our results demonstrate that combined HUMSC transplantation and quercetin treatment is a potential strategy for reducing secondary damage and promoting functional recovery following cerebral ischemia.
PubMed | Henan University of Science and Technology, The Affiliated Bayi Brain Hospital and Southern Medical University
Type: Journal Article | Journal: Genetics and molecular research : GMR | Year: 2015
We aimed to investigate the influence of lentiviral-mediated Bcl-2 overexpression in cerebral tissues of rats with acute cerebral infarction. Forty-five rats were randomly divided into sham, model, and treatment groups. The sham and model groups were administered a control lentiviral vector via the intracranial arteries 10 days before surgery, while the treatment group received lentivirus encoding a Bcl-2 overexpression vector. We induced cerebral artery infarction using a suture-occlusion method and analyzed the cerebral expression levels of apoptosis-related genes (caspase-3, Bax), total cerebral apoptosis, range of cerebral tissue infarction, and changes in nerve cell function after 72 h. The Bcl-2-encoding lentivirus was well expressed in rat cerebral tissues. The treatment group had significantly higher expression levels of Bcl-2 than the other two groups. After cerebral infarction, the model group had significantly increased expression levels of caspase-3 and Bax protein in cerebral tissues than the sham (P < 0.05). Expression of these apoptosis-related proteins in the treatment group was obviously lower than that in the model group (P < 0.05), but significantly higher than in the sham group (P < 0.05). Compared to sham, neuronal apoptosis levels and infarction range of cerebral tissues was increased in the model and treatment groups; however, these values in the treatment group were significantly lower than that in the model group (P < 0.05). Importantly, the treatment group had significantly decreased neurological impairment scores (P < 0.05). In conclusion, Bcl-2 over-expression can decrease neuronal apoptosis in rat cerebral tissue, and thus is neuroprotective after cerebral ischemia.
PubMed | Fudan University, CAS Institute of Genetics and Developmental Biology and The Affiliated Bayi Brain Hospital
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2014
The search for effective strategies for peripheral nerve regeneration has attracted much attention in recent years. In this study, ordered collagen fibers were used as intraluminal fibers after nerve injury in rats. Vascular endothelial growth factor (VEGF) plays an important role in nerve regeneration, but its very fast initial burst of activity within a short time has largely limited its clinical use. For the stable binding of VEGF to ordered collagen fibers, we fused a collagen-binding domain (CBD) to VEGF through recombinant DNA technology. Then, we filled the ordered collagen fibers-CBD-VEGF targeting delivery system in a collagen tube to construct natural neural scaffolds, which were then used to bridge transected nerve stumps in a rat sciatic nerve transection model. After transplantation, the natural neural scaffolds showed minimal foreign body reactions and good integration into the host tissue. Oriented collagen fibers in the collagen tube could guide regenerating axons in an oriented manner to the distal, degenerating nerve segment, maximizing the chance of target reinnervation. Functional and histological analyses indicated that the recovery of nerve function in the natural neural scaffolds-treated group was superior to the other grafted groups. The guiding of oriented axonal regeneration and effective delivery systems surmounting the otherwise rapid and short-lived diffusion of growth factors in body fluids are two important strategies in promoting peripheral nerve regeneration. The natural neural scaffolds described take advantage of these two aspects and may produce synergistic effects. These properties qualified the artificial nerve conduits as a putative candidate system for the fabrication of peripheral nerve reconstruction devices.
Jiang L.,Qingdao University |
Zhang Z.,The Affiliated Bayi Brain Hospital |
Li Z.,Qingdao University |
Yang S.,Qingdao University
International Journal of Clinical and Experimental Medicine | Year: 2016
Background: TNF induces inflammation in endothelial cells (ECs) but the mechanism at post-transcriptional levels is not fully understood. The purpose of this study is to elucidate the post-transcriptional factors regulating TNF-induced injury in HUVECs. Methods: To confirm the predicted miR-9500 is matched with AKT-1, 3’UTR luciferase activity of AKT-1 was used to assess. Then, HUVECs were exposed to TNF in the presence or absence of miR-9500, its mimics or inhibitors. The NF-κB signaling pathway is involved in TNF-induced chronic EC inflammation was investigated. Results: Luciferase reporter analysis showed that miR-9500 over-expression leads to decreased activity of luciferase gene fused with AKT1 3’-UTR as well as reduced AKT-1 expression in human HUVECs. Therefore, AKT-1 is direct targets of miR-9500. TNF resulted in markedly increased the up-expression of MMP-9, sICAM-1, and intercellular adhesion molecule 1 (ICAM-1) in HUVECS, whereas miR-9500 reduced expression of MMP-9, ICAM-1, and sICAM-1. Furthermore, miR-9500 substantially attenuated TNF-induced up-regulation expression of AKT-1 and NF-κB in HUVECs, respectively. But transfection with inhibitors of miR-9500, antagomiR-9500, overtly accentuated TNF-induced up-expression level of AKT-1 and NF-κB in HUVECs. MiR-9500 exerts effects on cell proliferation or viability of HUVECS, and accentuates caspase-dependent apoptosis. Conclusions: We identified miR-9500, which specifically bind to AKT1 mRNA 3’-UTR. MiR-9500 is a crucial mediator of endothelial inflammatory damage, and regulating expression of ICAM-1, sICAM-1, and MMP-9 at post-transcriptional levels, protecting against endothelial inflammatory damage through inhibiting the NF-κB signaling pathway. Moreover, it exerts effects on controlling viability and apoptosis of HUVECS. Our findings suggest that targeting miR-9500, being involved in chronic EC inflammation, is a promising strategy for the prevention and treatment of chronic inflammation associated diseases, including non-healing wound. © 2016, E-Century Publishing Corporation. All rights reserved.
PubMed | Capital Medical University and The Affiliated Bayi Brain Hospital
Type: | Journal: Clinical neurology and neurosurgery | Year: 2014
The purpose of this study is to provide a retrospective review of patients with brain stem cavernous malformation (BSCM) at single institution.Clinical courses were retrospectively reviewed for 38 consecutive patients who underwent microsurgical resection of symptomatic BSCMs in the sub-acute phase between January 2000 and December 2009. Microsurgery was performed with the help of intraoperative neuronavigation and neurophysiological monitoring. The baseline information of patients, lesion characteristics, surgical approaches, and follow-up outcomes were analyzed.All 38 patients received microsurgical resections without surgery-related mortality, and 37 patients were completely extirpated. 21 patients who experienced neurological deficits had functional improvement after surgery, 15 patients had no change in the neurological status over time to their preoperative condition or better, and 2 patients deteriorated. During the follow-up, 28 patients had resumed activities of daily living (KPS=90-100), 8 patients were able to self-care with some efforts (KPS=70-80) and other 2 patients needed considerable assistance. None of the operated patient had recurrent hemorrhage. Postoperative complications included new cranial nerve deficits in 13 patients, motor deficits in 3 patients, and new sensory disturbances in 6 patients.Complete surgical resection could be achieved through careful preoperative planning, selection of the optimal operative approach, a meticulous microsurgical technique and intraoperative navigation. However, taking into account the relatively high postoperative morbidity, complete resection is not always the goal for BSCMs, especially for those deep-seated lesions.
PubMed | The Affiliated Bayi Brain Hospital
Type: Journal Article | Journal: Experimental and therapeutic medicine | Year: 2016
A 62-year-old male suffering from vomiting and mild preceding nausea for 15 days was examined in the present case report. Magnetic resonance imaging revealed a homogeneously enhancing cluster-like lesion involving the lateral, third and fourth ventricles. An endoscopic biopsy was performed, and histopathological examination led to the diagnosis of a high-grade diffuse large B-cell lymphoma. To the best of our knowledge, the present study reports the first case of a primary lymphoma involving the entire ventricular system. Therefore, primary lymphomas should be considered in the list of ventricular tumors. An endoscopic biopsy requires minimal invasion to obtain an adequate tissue sample, and frequently leads to the correct diagnosis and subsequent treatment protocols.
PubMed | Capital Medical University and The Affiliated Bayi Brain Hospital
Type: Journal Article | Journal: PloS one | Year: 2016
Galactose-deficient IgA1 was evaluated in patients with IgA nephropathy(IgAN) and controls in order to determine the predictive value of galactose-deficient IgA1 in cases of IgA nephropathy.PubMed, EMBASE, Cochrane central register of controlled trials, CNKI, CBM disc, and VIP database were searched to identify eligible studies that evaluated a difference in aberrant IgA1 glycosylation in IgAN patients compared with controls. A meta-analysis was conducted to evaluate the impact of galactose-deficient IgA1(Gd-IgA1) levels in different groups.A total of 22 studies (n = 1657) met inclusion criteria. The mean Newcastle-Ottawa Scale (NOS) score was 7.2 and ranged from 6 to 8. The standard mean difference(SMD) in the meta-analysis of 20 studies of the level of Gd-IgA1 in the serum and/or supernatant of cultured cells was higher in the IgAN group compared with healthy controls as well as in those with other renal diseases (SMD = 1.76, 95% CI = 1.18-2.34, P<0.00001; SMD = 1.05, 95% CI = 0.05-2.04, P = 0.04). The data synthesis suggested that IgAN patients had similar levels of serum Gd-IgA1, with no significant differences, compared with first-degree relatives and Henoch-Schonlein purpura nephritis (HSPN) patients (MD = 0.04, 95% CI = 0.00-0.08, P = 0.05; MD = -46.03, 95% CI = -217.70-125.64, P = 0.60). In addition, the combined MD of 5 studies indicated that there were no significant differences in Gd-IgA1 levels among patients with varying severities of IgAN (MD = 0.02, 95% CI = -0.02-0.05, P = 0.28).The pooled evidence suggests that the level of Gd-IgA1 in the serum or supernatant of cultured cells from peripheral blood or tonsils may be a useful biomarker for predicting IgA nephropathy, though the level of Gd-IgA1 was not significantly associated with disease severity.