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"Song, Laijun"
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LncRNA FTX Involves in the Nogo-66-Induced Inhibition of Neurite Outgrowth Through Regulating PDK1/PKB/GSK-3β Pathway
2020
Nogo-66 can inhibit neurite outgrowth, while its regulation mechanisms have not been fully elucidated. Recent studies prove that lncRNAs are involved in neurite outgrowth. This study was aimed to investigate whether lncRNA FTX was involved in Nogo-66-induced inhibition of neurite outgrowth and explore the potential mechanism. The expression of relative genes was detected by qRT-PCR and western blot. The function of FTX was determined by overexpression and knockdown techniques. The interaction between FTX and PDK1 was evaluated by RIP and RNA pull-down assays. FTX expression was downregulated by Nogo-66 in PC12 cells. Nogo-66-induced inhibition of neurite outgrowth was relieved by FTX overexpression. FTX bound to PDK1 protein to disturb the interaction between PDK1 and E3 ubiquitin ligase RNF126, thereby blocked the ubiquitination degradation of PDK1 and elevated PDK1 protein level. Mechanically, FTX involved in the Nogo-66-induced inhibition of neurite outgrowth through the PDK1/PKB/GSK-3β pathway. In SCI rats, FTX knockdown inhibited neurite outgrowth induced by the receptor antagonist of Nogo-66. The present results suggested that FTX took part in Nogo-66-inhibited neurite outgrowth, and FTX exerted its function through regulating PDK1/PKB/GSK-3β pathway.
Journal Article
HAX-1 Protects Glioblastoma Cells from Apoptosis through the Akt1 Pathway
2017
Glioblastoma is the most common malignant tumor in central nervous system (CNS), and it is still insurmountable and has a poor prognosis. The proliferation and survival mechanism of glioma cells needs to be explored further for the development of glioma treatment. Hematopoietic-substrate-1 associated protein X-1 (HAX-1) has been reported as an anti-apoptosis protein that plays an important role in several malignant tumors. However, the effect and mechanism of HAX-1 in glioblastomas remains unknown. This study aimed to investigate the effect of HAX-1 in glioblastoma cells and explore the mechanism. The results of clone formation and Edu proliferation assay showed slower multiplication in HAX-1 knock-out cells. Flow cytometry showed cell cycle arrest mainly in G0/G1 phase. Apoptosis due to oxidative stress was increased after HAX-1 was knocked out. Western-blot assay exhibited that the levels of p21, Bax, and p53 proteins were significantly raised, and that the activation of the caspase cascade was enhanced in the absence of HAX-1. The degradation rate and ubiquitination of p53 declined because of the decrease in phosphorylation of proteins MDM2 and Akt1. Co-immunoprecipitation (Co-IP) and immunefluorescent co-localization assays were performed to test the influence of HAX-1 on the interaction between Akt1 and Hsp90, which is crucial for the activity of Akt1. In conclusion, this novel study suggested that HAX-1 could affect the Akt1 pathway through Hsp90. The knock-out of HAX-1 leads to the inactivity of the Ak1t/MDM2 axis, which leads to increased levels of p53, and finally generates cell cycle arrest and results in the apoptosis of glioblastoma cells.
Journal Article
Clinical analysis of syringomyelia resulting from spinal hemangioblastoma in a single series of 38 consecutive patients
by
Suresh, Vigneyshwar
,
Song, Laijun
,
Wang, Guoqing
in
Brain
,
Clinical features
,
Clinical outcomes
2019
•Patients with Middle duration of 6–12 months have a better prognosis.•The syringomyelia caused by SH were easily ignored because of its infrequency.•Improvement of spinal function grade may attribute to syringomyelia reduction.•SH accompanying syringomyelia should consider microsurgery as the first treatment.•It is a relatively large cohort of sporadic SH in a single center.
Syringomyelia was predominantly caused by Chiari malformation or intramedullary ependymoma. The goal of this study was to identify factors related to clinical outcomes and spinal hemangioblastoma (SH)-induced syringomyelia formation in a single series of patients.
Thirty-eight patients with SH were treated with microsurgery from January 2013 to December 2018. Clinical features and related factors were retrospectively analyzed in SH patients with and without syringomyelia.
Out of the total number of SH patients, 21 presented with remarkable syringomyelia, resulting in an incidence of 55.26% (21/38).Gross total resection was achieved in 36 cases (94.73%), and subtotal resection was obtained in 2 patients (5.27%). Neurological symptoms improved in 34 patients, remained stable in 2 patients and were aggravated in 2 cases during follow-up. In addition, there was a notable difference between the location of tumors and syringomyelia (P < 0.05). Syringomyelia occurred more frequently in the cervical segment than in any other spinal segment. Moreover, there was an association between symptom duration and clinical prognosis (P < 0.05). Ordinal regression analysis showed that the prognosis of middle duration groups (6–12 months) was better than early groups (0–6 months, p < 0.05, OR 20.21, 95%CI 2.34–336.97) and late groups (>12 months, p < 0.05, OR 11.54, 95%CI 1.30–102.21). Syringomyelia collapse or reduction occurred between two weeks and 15 months after surgery. An improvement of spinal function grade after surgery was more significant in syringomyelia reduction groups (p < 0.05).
The prevalence of syringomyelia due to SH is considerably high, and the initial clinical presentation of syringomyelia resulting from SH should be emphasized. Satisfactory outcomes were achieved by effective surgery in affected patients.
Journal Article
Corrigendum: HAX-1 Protects Glioblastoma Cells From Apoptosis Through the Akt1 Pathway
2019
[This corrects the article DOI: 10.3389/fncel.2017.00420.].
Journal Article
Successful treatment for giant pituitary adenomas through diverse transcranial approaches in a series of 15 consecutive patients
2012
Giant pituitary adenomas (GPAs) remain a therapeutic challenge with high mortality and morbidity. We described our experience in a consecutive series of GPAs with extensive suprasellar extension.
A series of 15 consecutive patients with maximum dimension of more than 4cm was enrolled in present study. These cases were microsurgically treated through diverse transcranial approach in our neurosurgical department from January 2006 to January 2011. Four different transcranial microsurgical approaches were selected based on tumor localization and expansion as well as neurosurgeon's experience.
Gross total removal (GTR) was achieved in 10 of all patients (67%), subtotal removal was achieved in 5 of 15 (33%). Nine patients experienced visual improvement postoperatively compared with those of preoperative symptom (82%), no intraoperative or postoperative death was observed in present series. The most striking features of this study indicate that an experienced team can reach 67% with no mortality, no panhypopituitarism and no permanent diabetes insipidus dealing with GPAs. No recurrent tumor was found in the GPAs with GTR, adjuvant radiation therapy had been performed in 5 patients and the continuous shrinkage of the residual adenomas was achieved in 2 out of 5 with radiotherapy.
Transcranial approach was still a relatively reliable and safe management for complex GPAs with extensive suprasellar extension.
Journal Article
Clinical study on microsurgical treatment for craniopharyngioma in a single consecutive institutional series of 335 patients
2018
•Low morbidity and mortality and the favorable outcomes were achieved in this study.•Tumor recurrence and surgical times contribute to negative resection.•Radiotherapy was considered when patients with disadvantageous removal factors.
The optimal management of craniopharyngioma is still controversial. The aim of this study is to explore microsurgical outcomes of craniopharyngioma in 335 cases.
Clinical data of 335 consecutive patients with craniopharyngioma between March 2011 and March 2017 were retrospectively analyzed.
Gross total resection (GTR) was achieved in 265 cases (79.1%), subtotal resection (STR) was obtained in 70 cases (20.9%). The GTR rate was 81.93% in pediatric group and 78.17% in adult group respectively, no significant difference regarding the GTR rate was found in adult group compared with in pediatric group (p > 0.05). However, there was a noticeable difference in the elevated hypothalamic obesity in children group compared with in adult group after operation (p < 0.05). Multivariate analysis indicated that the tumor recurrence and surgical times played a negative role in the resection extent, the odds ratio and 95% confidence interval of the tumor recurrence and surgical times is [0.306 (0.155–0.603), (p < 0.01)] and [2.135 (1.101–4.142), (p < 0.05)] respectively. There was significant difference on panhypopituitarism between GTR and STR group (p < 0.05). However, No significant difference regarding the postoperative visual dysfunction and indepent quality of life respectively between GTR and STR group was found (p > 0.05). Additionally, there were no statistically significant differences for recurrence-free curves between GTR and STR plus adjuvant radiotherapy (p > 0.05).
Present findings demonstrated that tumor recurrence and surgical times contribute to negative total resection for craniopharyngioma. Postoperative precise adjuvant radiotherapy was considered in selected cases if pursuit of GTR was rather dangerous under disadvantageous removal factors.
Journal Article
Pro-apoptotic effect of TRAIL-transfected endothelial progenitor cells on glioma cells
2018
Glioma is one of the most common aggressive neuroepithelial malignant tumors in the central nervous system. It has a high recurrence rate and poor prognosis, primarily due to the fact that novel therapeutic agents cannot penetrate the blood-brain barrier (BBB). Endothelial progenitor cells (EPCs) have been reported to move across the BBB and access the tumor site. However, whether EPCs expressing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce glioma cell apoptosis requires further investigation. In the present study, EPCs were transfected and stably expressed with TRAIL through lentiviral infection. The pro-apoptotic effect of these TRAIL-expressing EPCs on the SHG44 glioma cell line was investigated. The migration ability of TRAIL-expressing EPCs toward SHG44 cells through the Transwell culture system was investigated via a high-content screening assay. The apoptotic rate and the expression of cleaved caspase-8 and −3 in addition to the cleaved poly(ADP-ribose) polymerase in SHG44 cells significantly increased in the TRAIL-overexpressing EPC treatment group compared with the controls. The increased apoptotic rate was reversed using a caspase inhibitor. The findings suggested that the TRAIL-expressing EPCs induced apoptosis in the SHG44 cells by activating the death receptor pathway, indicating that the TRAIL-expressing EPCs may be a useful strategy for glioma treatment.
Journal Article
Activating transcription factor 3 is overexpressed in human glioma and its knockdown in glioblastoma cells causes growth inhibition both in vitro and in vivo
by
SONG, LAIJUN
,
MA, SIQI
,
GUO, FUYOU
in
activating transcription factor 3
,
Angiogenesis
,
Brain cancer
2015
Glioblastomas are highly malignant gliomas that are extremely invasive with high rates of recurrence and mortality. It has been reported that activating transcription factor 3 (ATF3) is expressed in elevated levels in multiple malignant tumors. The purpose of this study was to investigate the function of ATF3 in the development of glioma and its clinical significance. Immunohistochemical staining, western blot analysis and RT-qPCR revealed that the mRNA and protein levels of ATF3 and matrix metalloproteinase 2 (MMP2) were higher in the glioma than in the normal human brain tissues, and that their levels were proportional to the pathological grades. By contrast, the mRNA and protein levels of mammary serine protease inhibitor (maspin; SERPINB5) were significantly lower in the glioma than in the normal brain tissue, and maspin expression was inversely proportional to the glioma pathological grade. The transfection of U373MG glioblastoma cells with ATF3-siRNA induced a number of changes in cell behavior; the cell proliferative activity was decreased and flow cytometry revealed an increased proportion of cells arrested in the G0/G1 phase of the cell cycle. In addition, TUNEL staining indicated an increased proportion of cells undergoing apoptosis and Transwell assays revealed impaired cell mobility. The sizes of the tumors grown as xenografts in nude mice were also significantly reduced by treatment of host mice with ATF3-siRNA. Taken together, these results suggest that ATF3 promotes the progression of human gliomas.
Journal Article
Clinical features and risk factor analysis for lower extremity deep venous thrombosis in Chinese neurosurgical patients
2015
Background: Deep venous thrombosis (DVT) contributes significantly to the morbidity and mortality of neurosurgical patients; however, no data regarding lower extremity DVT in postoperative Chinese neurosurgical patients have been reported. Materials and Methods: From January 2012 to December 2013, 196 patients without preoperative DVT who underwent neurosurgical operations were evaluated by color Doppler ultrasonography and D-dimer level measurements on the 3rd, 7th, and 14th days after surgery. Follow-up clinical data were recorded to determine the incidence of lower extremity DVT in postoperative neurosurgical patients and to analyze related clinical features. First, a single factor analysis, Chi-square test, was used to select statistically significant factors. Then, a multivariate analysis, binary logistic regression analysis, was used to determine risk factors for lower extremity DVT in postoperative neurosurgical patients. Results: Lower extremity DVT occurred in 61 patients, and the incidence of DVT was 31.1% in the enrolled Chinese neurosurgical patients. The common symptoms of DVT were limb swelling and lower extremity pain as well as increased soft tissue tension. The common sites of venous involvement were the calf muscle and peroneal and posterior tibial veins. The single factor analysis showed statistically significant differences in DVT risk factors, including age, hypertension, smoking status, operation time, a bedridden or paralyzed state, the presence of a tumor, postoperative dehydration, and glucocorticoid treatment, between the two groups (P < 0.05). The binary logistic regression analysis showed that an age greater than 50 years, hypertension, a bedridden or paralyzed state, the presence of a tumor, and postoperative dehydration were risk factors for lower extremity DVT in postoperative neurosurgical patients. Conclusions: Lower extremity DVT was a common complication following craniotomy in the enrolled Chinese neurosurgical patients. Multiple factors were identified as predictive of DVT in neurosurgical patients, including the presence of a tumor, an age greater than 50 years, hypertension, and immobility.
Journal Article