Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most lethal primary malignant brain tumor in adults with poor survival due to acquired therapeutic resistance and rapid recurrence. Currently, the standard clinical strategy for glioma includes maximum surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy; however, the median survival of patients with GBM remains poor despite these comprehensive therapies. Therefore, the identification of new prognostic biomarkers is urgently needed to evaluate the malignancy and long-term outcome of glioma. AIMS: To further investigate prognostic biomarkers and potential therapeutic targets for GBM. RESULTS: In this study, we identified tribbles pseudokinase 2 (TRIB2) as one of the genes that is most correlated with pathological classification, radioresistance, and TMZ resistance in glioma. Additionally, the expression of mitogen-activated protein kinase kinase kinase 1 (MAP3K1) showed a strong correlation with TRIB2. Moreover, a combined increase in TRIB2 and MAP3K1 was observed in GBM and indicated a poor prognosis of patients with glioma. Finally, enriched TRIB2 expression and MAP3K1 expression were shown to be associated with resistance to TMZ and radiotherapy. CONCLUSION: Combined elevation of TRIB2 and MAP3K1 could be novel prognostic biomarkers and potential therapeutic targets to evaluate the malignancy and long-term outcomes of GBM.

Retraction: Receptor tyrosine kinase AXL is correlated with poor prognosis and induces temozolomide resistance in glioblastoma.

Retraction: Receptor tyrosine kinase AXL is correlated with poor prognosis and induces temozolomide resistance in glioblastoma, CNS Neuroscience & Therapeutics 2019, (https://doi.org/10.1111/cns.13227). The above article published online on 02 October 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief Jun Chen, and John Wiley & Sons Ltd. The retraction has been agreed due to unreliable data and consequently its misleading results and conclusions.

DAPT suppresses the proliferation of human glioma cell line SHG-44.

OBJECTIVE: To explore the suppressing effect of γ-secretase inhibitor DAPT on proliferation of human glioma cell line SHG-44 in vitro and its mechanism. METHODS: The SHG-44 cell was treated by DAPT with different concentration. The proliferation of cells was detected by MTT assay; cell cycle and TSC of CD133(+) were determined by flow cytometry analysis technique; the key factor in Notch signaling pathway (Notch-1, Delta-1, Hes-1) was measured by reverse transcriptase-polymerase chain reaction and western blotting. RESULTS: DAPT inhibited the growth and proliferation of SHG-44 cells significantly(P<0.05). And the inhibiting effect on SHG-44 cells produced by DAPT showed a dose-dependent manner. DAPT increased the rate of cells in G0/G1 phase of SHG-44 cells, while it decreased the rate of cells in S phase. TSC of CD133(+) was significantly reduced after DAPT treated SHG-44 cells. The expression of protein and mRNA of Notch-1, Delta-1 and Hes-1 were gradually downregulated with the increase of DAPT doses. CONCLUSIONS: DAPT can downregulate these key factor in Notch signaling pathway, reduce the TSC of CD133+ and inhibit the proliferation of SHG-44 cells.

Neuroprotective effect of allicin against traumatic brain injury via Akt/endothelial nitric oxide synthase pathway-mediated anti-inflammatory and anti-oxidative activities.

Allicin, one of the main biologically active compounds derived from garlic, has been shown to exert various anti-oxidative and anti-inflammatory activities in in vitro and in vivo studies. Here, we sought to investigate the potential neuroprotective effects of allicin against traumatic brain injury (TBI) in rats. We found that allicin treatment (10 and 50mg/kg, not 1mg/kg) significantly reduced brain edema and motor functional deficits, as well as apoptotic neuronal cell death in injured cortex. These protective effects could be observed even if the administration was delayed to 4h after injury. Moreover, allicin treatment decreased the expression levels of MDA and protein carbonyl, preserved the endogenous antioxidant enzyme activities, and suppressed the expression of inflammatory cytokines. The results of Western blot analysis showed that allicin increased the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). Blocking Akt/eNOS pathway activation by specific inhibitor LY294002 (10µL, 10mmol/L) or L-NIO (0.5mg/kg) partly reversed the protective effects of allicin and its anti-inflammatory activities. The allicin induced anti-oxidative activity was partly prevented by LY294002, but not L-NIO. In summary, our data strongly suggested that allicin treatment at an appropriate dose can exert protective effect against TBI through Akt/eNOS pathway-mediated anti-inflammatory and anti-oxidative activities.

Effect of ERBB2 expression on invasiveness of glioma TJ905 cells.

OBJECTIVE: To investigate the influence and possible mechanism of ERBB2 expression on the invasiveness of glioma cells. METHODS: Glioma TJ905 cells were separated and cultured. ERBB2 shRNA and overexpressing vectors were constructed, which were then transfected. The ERBB2 expression was up-regulated or down-regulated. Changes of invasiveness of TJ905 cells were detected by Transwell assay, and the expressions of matrix metalloprotease (MMP)-2 and MMP-9 were measured by Western blot. RESULTS: ERBB2 shRNA transfection vector could effectively inhibit expression of ERBB2; while ERBB2 overexpressing vector transfection could significantly improve the expression of ERBB2 in TJ905 cells. Transwell assay showed that when ERBB2 expression was down-regulated, the invasiveness of TJ905 cells was notably decreased; when ERBB2 expression was up-regulated, the invasiveness of TJ905 cells was markedly increased. Meanwhile, Western blot indicated that down-regulating ERBB2 inhibited the expression of MMP-2 and MMP-9, while up-regulating ERBB2 enhanced their expressions. CONCLUSIONS: ERBB2 expression is closely related to the invasiveness of glioma TJ905 cells.

[The early diagnosis and therapy of aneurismal subarachnoid hemorrhage].

OBJECTIVE: To discuss the early diagnostic methods and therapeutic principles of aneurysmal subarachnoid hemorrhage (SAH), and evaluate the therapeutic efficacy objectively. METHODS: Using neuro-imaging examinations combined with case history and clinical symptoms to make the early diagnosis of 96 case with aneurysmal SAH, and Guglielmi detachable microcoil (GDC) was utilized for early intracapsular embolization in the ruptured aneurysms. Efficient symptomatic treatment was done early after operation. RESULTS: All of 96 cases were early diagnosed and successfully embolized; Among them, the aneurysmal lumen was 100% occluded in 83 cases, 95% in 8 cases, 90% in 5 cases. There were 3 cases complicating with aneurysms rupture during operation, 5 cases with cerebral vasospasm. One case was affected by microcoil terminal escape after operation, 3 recurrent cases were all cured with secondary GDC embolization. There were 9 complications associated with embolization techniques and 13 cases (13.5%) occurring permanent sequelae associated with SAH. According to the Glasgow prognosis score, 77 patients got grade I, 7 grade II, 6 grade III, 3 grade IV, and 3 grade V. The mortality rate was 3.1%. CONCLUSIONS: To make early etiological diagnosis of the SAH patients, using GDC to embolize the aneurysms, and earlier efficient symptomatic treatment are important methods to improve the curative rate and reduce the mortality rate.