MiR-760 exerts a critical regulatory role in glioma proliferation, migration, and invasion by modulating MMP2 expression.

Background: Glioma represents the predominant subtype of brain tumor, characterized by an unfavorable prognosis. Current evidence indicates the involvement of microRNAs (miRNAs) in the initiation and progression of glioma malignancies. While miR-760 has been recognized in the context of tumorigenesis, its precise role in gliomas remains insufficiently explored. Methods: In this investigation, we harnessed the GSE25631 database to scrutinize the aberrant expression profiles of microRNAs, whereby the diminished expression of miR-760 in glioblastoma was validated. Our aim was to delineate the expression patterns of microRNA-760 (miR-760) and probe its prognostic significance within the realm of glioma. Employing quantitative real-time polymerase chain reaction, we ascertained the relative expression levels of miR-760 and MMP2 in glioma cell lines. The impact of miR-760 on cell proliferation, migration, and invasion was assessed through Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assays. Bioinformatics analysis corroborated the downstream target gene of miR-760. Furthermore, a luciferase reporter experiment was conducted to pinpoint MMP2 as the direct target gene of miR-760. The assessment of MMP2 protein levels was accomplished through Western blotting and immunofluorescence techniques. Result: Our data unequivocally revealed a substantial reduction in miR-760 expression within glioma tissues and cell lines. Heightened miR-760 levels exerted a restraining influence on the proliferation, migration, and invasion capabilities of glioma cell lines. The outcomes of our bioinformatics analysis unveiled the ability of miR-760 to engage with and curtail MMP2 expression. Collectively, these findings posit that miR-760 exerts a restraining influence on glioma growth by orchestrating the upregulation of miR-760 along the miR-760/MMP2 axis. Conclusion: The delineation of the miR-760/MMP2 axis promises to broaden our comprehension of the intricate molecular mechanisms underpinning glioma proliferation and may unveil prospective therapeutic avenues for the management of glioma.

Sinomenine Protects against Early Brain Injury by Inhibiting Microglial Inflammatory Response via Nrf2-Dependent Pathway after Subarachnoid Hemorrhage.

Microglial activation and sustained inflammation plays an important role in the processes of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Sinomenine (SIN) has been demonstrated to have neuroprotective effects in the traumatic brain injury (TBI) model. However, the role of SIN in SAH-induced EBI and its latent mechanisms remain unclear. This study was carried out to explore the role of SIN on SAH-induced EBI and its effects on the microglial inflammatory response following SAH. In this study, a model of SAH in rats was established. Modified neurological severity scores (mNSS), encephaledema, and Nissl staining were employed to determine the effects of SIN. Western blot and immunofluorescence analysis were performed to evaluate nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Nrf2-related downstream proteins, including heme oxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO-1), were detected with immunohistochemistry analyses and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Microglia activation and associated inflammatory factors, factor-kappa B (NF-κB), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), were assessed after SAH. The results showed that SIN administration improved neurobehavior function, and attenuated neural apoptosis and brain edema after SAH. In addition, SIN inhibited microglial action and the subsequent inflammatory response after SAH through the upregulated expression of HO-1 and NQO-1 via activation of the Nrf2 pathway. These results demonstrated that SIN supplementation provided protection against SAH-induced neuronal apoptosis by microglial inflammatory response regulation and possible involvement of the Nrf2 pathway.

Preliminary clinical application of multimodal imaging combined with frameless robotic stereotactic biopsy in the diagnosis of primary central nervous system lymphoma.

Objective: To evaluate the clinical application of multimodal imaging combined with frameless robotic stereotactic biopsy in the diagnosis of primary central nervous system lymphoma (PCNSL). Methods: We retrospectively reviewed the clinical data of 8 patients who were considered suspected cases of PCNSL by multimodal imaging techniques. The final pathologic diagnosis were determined by the frameless robotic stereotactic biopsy. The postoperative related complications and pathological results were analyzed. Results: All patients underwent biopsies under general anesthesia with an average surgery time of 29.5 ± 4.5 min. The final pathological diagnostic accordant rate with the preoperative ones was 100%, and the pathologic examination of our patients showed features of diffuse large B-cell lymphoma. During the surgery, one patient suffered intratumoral hemorrhage without leading to serious cerebral edema, and conservative treatment was given. There was no death occurring during the study, and there were no significant differences in the Karnofsky Performance Scale Scores of all patients before and after surgery. Finally, they were transferred to the hematology department for standardized chemoradiotherapy according to the pathological results of PCNSL. Conclusion: This study shows that it may play a vital role in the early diagnosis of PCNSL with the technique of multimodal imaging. The technique of frameless robotic stereotactic biopsy for obtaining the pathology outcomes in suspected PCNSL patients has the advantages of safety, efficiency, and minimally invasiveness.

Clinical Study on a Modified Hematoma Puncture Drainage Treatment in Patients with Hypertensive Basal Ganglia Hemorrhage.

OBJECTIVE: We aim to investigate the clinical efficacy and safety of a modified hematoma puncture drainage treatment through the burr hole lateral to Kocher's point from the frontal lobe in patients with hypertensive basal ganglia hemorrhage. METHODS: Twenty-six patients were enrolled in the retrospective study. The volume of hematoma in those patients was between 25 and 35 mL, and the Glasgow Coma Scale scores were between 9 and 11; they were divided into a hematoma puncture drainage treatment group and a traditional conservative treatment group. The volume of remaining hematoma, neurological function defect scores, and life quality after treatment, duration of hospitalization, and cost of hospitalization were analyzed in these 2 groups. RESULTS: The volume of remaining hematoma was significantly less in the drainage group than that in the traditional group on the first day and the third day after treatment (P < 0.05). Posttreatment neurological function defect scores in the drainage group were statistically lower than those in the traditional group (P < 0.05). The duration of hospitalization was significantly shorter and the cost of hospitalization was also significantly less in the drainage group than that in the traditional group (P < 0.05). The Extended Glasgow Outcome Scale and Barthel Index scores were significantly higher in the drainage group than those in the traditional group (P < 0.05). There were no significant differences between the 2 groups in the complication rates (P > 0.05). CONCLUSIONS: The modified hematoma puncture drainage treatment represents an effective and safe way to treat hypertensive basal ganglia hemorrhage.

Sirtuin 1 alleviates microglia-induced inflammation by modulating the PGC-1α/Nrf2 pathway after traumatic brain injury in male rats.

Microglial activation and the subsequent inflammatory response play important roles in the central nervous system after traumatic brain injury (TBI). Activation of the PGC-1α pathway is responsible for microglial activation after TBI. Our previous study demonstrated that SIRT1 alleviates neuroinflammation-induced apoptosis after TBI, and activation of the PGC-1α/Nrf2 pathway extenuates TBI-induced neuronal apoptosis. However, no study has investigated whether SIRT1 can affect the PGC-1α/Nrf2 pathway to induce microglial excitation and the subsequent neuroinflammatory response. Microglial activation and the levels of pro-inflammatory factors, namely, tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were assessed to evaluate the neuroinflammatory response after TBI. To examine the effects of SIRT1, immunohistochemical staining and western blot analysis were used to observe the nuclear translocation and secretion of PGC-1α, as well as the activation of the PGC-1α/Nrf2 pathway. Treatment with the SIRT1 inhibitor sirtinol promoted microglial activation and pro-inflammatory factor expression (TNF-α, IL-6, and IL-1ß) and inhibited PGC-1α and Nrf2 nuclear translocation and secretion after TBI, while treatment with the SIRT1 activator A3 had the opposite effects. The results of this study suggest that microglial activation, the subsequent neuroinflammatory response, and the PGC-1α/Nrf2 pathway play essential roles in secondary injury after TBI. These results indicate that SIRT1 protects neurons after TBI by inhibiting microglial activation and the subsequent inflammatory response, possibly by activating the PGC-1α/Nrf2 pathway.

LncRNA WEE2-AS1 Knockdown Inhibits the Proliferation, Migration and 3 Invasion of Glioma Cells via Regulating miR-29b-2-5p/TPM3 Axis.

Glioma is a general malignant tumor with a dismal prognosis. Long noncoding RNAs (lncRNAs) have been implicated in the initiation and processes of tumors. An investigation of the GEPIA database revealed that long noncoding RNA WEE2 antisense RNA 1 (WEE2-AS1) is upregulated in glioma tissues compared to normal brain tissues, and validation with quantitative real-time polymerase chain reaction (qRT-PCR) revealed that WEE2-AS1 expression was consistent with the database prediction. Fluorescence in situ hybridization (FISH) assays revealed that WEE2-AS1 was localized primarily in the cytoplasm. Clone formation experiment and EDU assay were used to detect cell proliferation ability, and Transwell assay was used to detect cell migration and invasion ability, Western-blot assay and immunofluorescence were used to determine TPM3 protein level. Functional experiments revealed that the downregulation of WEE2-AS1 impeded cell proliferation, migration, and invasion in glioma cell lines. Furthermore, downregulation of WEE2-AS1 suppressed tumor growth in vivo. Bioinformatics predictions and integrated experiments indicated that WEE2-AS1 promoted tropomyosin 3 (TPM3) expression by sponging miR-29b-2-5p. A dual-luciferase reporter assay was conducted to uncover the binding of WEE2-AS1 and miR-29b-2-5p and that of miR-29b-2-5p and TPM3. Additionally, a series of rescue assays showed that WEE2-AS1 promotes proliferation, migration, and invasion by targeting miR-29b-2-5p to regulate TPM3 expression. Ultimately, the results of this study indicate that WEE2-AS1 plays an oncogenic role in glioma and may promote further investigations of the diagnostic and prognostic value of WEE2-AS1 in glioma.

LncRNA WEE2-AS1 knockdown inhibits the proliferation, migration and invasion of glioma cells via regulating miR-29b-2-5p/TPM3 axis.

Glioma is a general malignant tumor with a dismal prognosis. Long noncoding RNAs (lncRNAs) have been implicated in the initiation and processes of tumors. An investigation of the GEPIA database revealed that long noncoding RNA WEE2 antisense RNA 1 (WEE2-AS1) is upregulated in glioma tissues compared to normal brain tissues, and validation with quantitative real-time polymerase chain reaction (qRT-PCR) revealed that WEE2-AS1 expression was consistent with the database prediction. Fluorescence in situ hybridization (FISH) assays revealed that WEE2-AS1 was localized primarily in the cytoplasm. Clone formation experiment and EDU assay were used to detect cell proliferation ability, and Transwell assay was used to detect cell migration and invasion ability, Western-blot assay and immunofluorescence were used to determine TPM3 protein level. Functional experiments revealed that the downregulation of WEE2-AS1 impeded cell proliferation, migration, and invasion in glioma cell lines. Furthermore, downregulation of WEE2-AS1 suppressed tumor growth in vivo. Bioinformatics predictions and integrated experiments indicated that WEE2-AS1 promoted tropomyosin 3 (TPM3) expression by sponging miR-29b-2-5p. A dual-luciferase reporter assay was conducted to uncover the binding of WEE2-AS1 and miR-29b-2-5p and that of miR-29b-2-5p and TPM3. Additionally, a series of rescue assays showed that WEE2-AS1 promotes proliferation, migration, and invasion by targeting miR-29b-2-5p to regulate TPM3 expression. Ultimately, the results of this study indicate that WEE2-AS1 plays an oncogenic role in glioma and may promote further investigations of the diagnostic and prognostic value of WEE2-AS1 in glioma.

Preliminary results of posterior contralateral cervical 7 nerve transposition in the treatment of upper limb plegia after a stroke.

OBJECTIVE: This study aimed to explore a shorter and safer contralateral C7 transposition pathway for the treatment of central upper limb paralysis. METHODS: From July 2018 to March 2019, 10 patients with central upper limb paralysis underwent posterior cervical 7 nerve transposition. The age of these patients ranged within 31-58 years old (average: 44 years old). These patients comprised of eight male patients and two female patients. Nine patients had cerebral hemorrhage, and one patient had a cerebral infarction. Furthermore, nine patients presented with spastic paralysis of the upper limbs and one patient presented with nonspastic paralysis. The duration of plegia before the operation ranged from 6 to 60 months (average: 26 months). The surgical procedure included transposition of the contralateral cervical 7 nerve root via a posterior vertebral approach under general anesthesia, and the distal part of the contralateral cervical 7 nerve was anastomosed with the proximal part of the ipsilateral cervical 7 nerve. RESULTS: The length of the contralateral cervical 7 nerve was 5.16 ± 0.21 cm, which was directly anastomosed with the ipsilateral cervical 7 nerve. Neither case needed nerve transplantation. Most patients had temporary numbness in their healthy fingers, which all disappeared within three months. Up to now, the follow-up results are as follows: The spasticity of the affected upper limbs in five patients is lower than that before the operation, the pain and temperature sensation of the affected upper limbs in six patients are better than before the operation. CONCLUSION: The distance of nerve transposition can be shortened by a posterior vertebral approach operation, where the contralateral C7 nerve can be anastomosed directly with the ipsilateral C7 nerve which may be effective for nerve regeneration and functional recovery. However, this conclusion still needs further research and verification.

Neuroprotection by quercetin via mitochondrial function adaptation in traumatic brain injury: PGC-1α pathway as a potential mechanism.

The aim of this study was to investigate the neuroprotective effects of quercetin in mouse models of traumatic brain injury (TBI) and the potential role of the PGC-1α pathway in putative neuroprotection. Wild-type mice were randomly assigned to four groups: the sham group, the TBI group, the TBI+vehicle group and the TBI+quercetin group. Quercetin, a dietary flavonoid used as a food supplement, significantly reduced TBI-induced neuronal apoptosis and ameliorated mitochondrial lesions. It significantly accelerated the translocation of PGC-1α protein from the cytoplasm to the nucleus. In addition, quercetin restored the level of cytochrome c, malondialdehyde and superoxide dismutase in mitochondria. Therefore, quercetin administration can potentially attenuate brain injury in a TBI model by increasing the activities of mitochondrial biogenesis via the mediation of the PGC-1α pathway.

Fucoxanthin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE and Nrf2-autophagy pathways.

Fucoxanthin is abundant in seaweed and is considered as a powerful antioxidant. It has been proposed to possess anti-cancer, anti-obesity and anti-diabetes effects. However, its roles in brain injury models have not been fully understood. The objective of this study was to investigate the neuroprotection of fucoxanthin in models of traumatic brain injury (TBI) and the role of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant-response element (ARE) and Nrf2-autophagy pathways in the putative neuroprotection. We found that fucoxanthin alleviated TBI-induced secondary brain injury, including neurological deficits, cerebral edema, brain lesion and neuronal apoptosis. Moreover, the up-regulation of malondialdehyde (MDA) and the activity of glutathione peroxidase (GPx) were reversed by fucoxanthin treatment. Furthermore, our in vitro studies demonstrated that fucoxanthin increased the neuron survival and reduced the reactive oxygen species (ROS) level. In addition, fucoxanthin activated the Nrf2-ARE pathway and autophagy both in vivo and in vitro, which was proven by the results of immunohistochemistry, western blot and electrophoretic mobility shift assay (EMSA). However, fucoxanthin failed to provide neuroprotection and activated autophagy following TBI in Nrf2-/- mice. In conclusion, our studies indicated that fucoxanthin provided neuroprotective effects in models of TBI, potentially via regulation of the Nrf2-ARE and Nrf2-autophagy pathways.

Protective Effects of Quercetin on Mitochondrial Biogenesis in Experimental Traumatic Brain Injury via the Nrf2 Signaling Pathway.

The present investigation was carried out to elucidate a possible molecular mechanism related to the protective effect of quercetin administration against oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in mitochondrial biogenesis. Recently, quercetin has been proved to have a protective effect against mitochondria damage after traumatic brain injury (TBI). However, its precise role and underlying mechanisms in traumatic brain injury are not yet fully understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism of these effects in a weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administrated 30 min after TBI. In this experiment, ICR mice were divided into four groups: A sham group, TBI group, TBI + vehicle group, and TBI + quercetin group. Brain samples were collected 24 h later for analysis. Quercetin treatment resulted in an upregulation of Nrf2 expression and cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were restored by quercetin treatment. Quercetin markedly promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus. These observations suggest that quercetin improves mitochondrial function in TBI models, possibly by activating the Nrf2 pathway.

Quercetin induces mitochondrial biogenesis in experimental traumatic brain injury via the PGC-1α signaling pathway.

Quercetin, a dietary flavonoid used as a food supplement, has been found to have protective effect against mitochondria damage after traumatic brain injury (TBI) in mice. However, the mechanisms underlying these effects are still not well understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism mediating these effects in the weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administration 30 min after TBI. Brain samples were collected 24 h later for analysis. Quercetin treatment upregulated the expression of PGC-1α and restored the level of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD). These results demonstrate that quercetin improves mitochondrial function in mice by improving the level of PGC-1α following TBI.

Quercetin blocks t-AUCB-induced autophagy by Hsp27 and Atg7 inhibition in glioblastoma cells in vitro.

We previously demonstrated that the acquired resistance because of Hsp27 activation weakens the cytotoxic effect of t-AUCB on glioblastoma cells. Since autophagy is regarded as a survival mechanism for cells exposed to cytotoxic agents, the aim of this study is to investigate whether t-AUCB induces autophagy and whether Hsp27 and autophagy are interacted with each other. Our data demonstrated that t-AUCB induces autophagy in glioblastoma cells and regulates multiple autophagy related-gene expression. t-AUCB induces overexpression of Atg7, which is downstream of Hsp27 and participates in the resistance of glioblastoma cells to t-AUCB treatment. Hsp27 inhibitor quercetin suppresses Atg7 expression and strengthens t-AUCB-induced cell death by autophagy blockage. We concluded that combination of quercetin and t-AUCB might be a potential strategy for glioblastoma treatment.

Quercetin sensitizes glioblastoma to t-AUCB by dual inhibition of Hsp27 and COX-2 in vitro and in vivo.

BACKGROUND: Evidences indicate that inflammatory process plays pivotal role in tumor disease. Soluble epoxide hydrolase inhibitors (sEHIs) have been shown to participate in anti-inflammation and tumorigenesis by protecting epoxyeicosatrienoic acids (EETs). Although we have previously revealed some effects of t-AUCB on glioma in vitro, further investigations are needed to demonstrate its effects on glioblastoma growth in vivo and how to strengthen its antitumor effect. METHODS: CCK-8 kit was used to test cell growth. Cell migration capacity was performed by wound healing assays. Transwell assay was used to test cell invasion potency. Cell-cycle analysis and cell apoptosis was performed by flow cytometry. The activity of caspase-3 in cells was measured using caspase-3 activity assay kits. Total RNA was extracted from cells lysated by TRIzol reagent. qRT-PCR was performed by ABI 7500 fast RT- PCR system. Lipofectamine RNAiMAX Transfection Reagent (Invitrogen) was used for siRNA transfection. Western blootting was used to test protein expression. Tumor cell xenograft mouse models were used for in vivo study. The SPSS version 17.0 software was applied for statistical analysis. RESULTS: Our data shown that t-AUCB inhibits cell proliferation, migration and invasion and induces cell cycle G1 phase arrest in vitro but induces no cell apoptosis; increased Hsp27 activation and following COX-2 overexpression confer resistance to t-AUCB treatment in glioblastoma both in vitro and in vivo; quercetin sensitizes glioblastoma to t-AUCB by dual inhibition of Hsp27 and COX-2 in vitro and in vivo. CONCLUSIONS: These results indicate that combination of t-AUCB and quercetin may be a potential approach to treating glioblastoma.

Huge Frontal-Temporal Lobe Arachnoid Cyst Presenting as an Weariness Migraine.

To the authors' knowledge, most of intracranial arachnoid cyst located in middle cranial fossa and lateral fissure cistern. So, huge frontal-temporal lobe arachnoid cyst is rare. Symptoms of arachnoid cyst may be atypical, including headache, nausea, vomiting, epilepsy, poor memory, and so on. Of course, migraine related to weariness is a rare benign headache disorder. The authors reported a patient presenting with weariness migraine associated with large frontal-temporal lobe arachnoid cyst.

Lentivirus-Mediated Knockdown of TCTN1 Inhibits Glioma Cell Proliferation.

Tectonic-1, also named as TCTN1 or TECT1, which belongs to a family of signal-sequence-containing secreted and transmembrane proteins evolutionarily conserved among eukaryotes, was reported to be involved in central nervous system development and ciliogenesis. In this paper, we found that TCTN1 is extensively expressed in human glioma cell lines. To clarify the role of TCTN1 in glioma, we employed lentivirus-mediated short hairpin RNA to knock down TCTN1 expression in U251 and U87MG glioma cells. Knockdown of TCTN1 potently inhibited cell proliferation, as determined by MTT and colony formation assays. Cell cycle analysis showed depletion of TCTN1 led to both U251 and U87MG cells arrested in the G0/G1 phase. These data suggest TCTN1 is essential for glioma cell viability, and dysregulation of TCTN1 may play a key role in glioma tumorigenesis.

Differential expression of microRNAs in postoperative radiotherapy sensitive and resistant patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and more resistant to radiotherapy. However, hetero-radiosensitivity occurs in different patients. MicroRNAs (miRNAs) play important roles in the initiation and progression of a multitude of tumors. The study aims to examine the different microRNAs expression profiles of postoperative radiotherapy sensitive and resistant patients with GBM, to make an inquiry about their potential role and discover a certain set of radio-sensitivity markers. Three paired samples from six GBM patients who had only been treated with postoperative radiotherapy were selected, and then, they were divided into radiotherapy sensitive group and resistant group according to their overall survivals, local recurrence rates, and Karnofsky Performance Scale scores. Expression profiles of miRNAs in these two groups were determined by the method of microarray assay. Comparing with resistant patients, 13 miRNAs were significantly upregulated and 10 miRNAs were greatly downregulated in sensitive group. Among them, four miRNAs were validated by quantitative RT-PCR. The differentially expressed miRNAs and their putative target genes were revealed by bioformatic analysis to play a role in cell signaling, proliferation, aging, and death. High-enrichment pathway analysis identified that some classical pathways participated in numerous metabolic processes, especially in cell cycle regulation, such as mTOR, MAPK, TGF-beta, and PI3K-Akt signaling pathways. Our research will contribute to identifying clinical diagnostic markers and therapeutic targets in the treatment of GBM by postoperative radiotherapy.

Knockdown of nuclear factor erythroid 2-related factor 2 by lentivirus induces differentiation of glioma stem-like cells.

Glioma stem cells (GSCs) are key in the progression and recurrence of glioblastoma. Inducing the differentiation of GSCs is an important therapeutic target for glioblastoma. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been reported to be important in maintaining the stem cell status of GSCs; however, its association with differentiation has not been studied. Herein, we knocked down Nrf2 from GSCs to investigate the role of Nrf2 in the differentiation of GSCs. First, Nrf2 expression was observed at different stages of differentiation; then, Nrf2 was knocked down and the association of Nrf2 with differentiation degree was observed in vitro. Finally, GSCs were planted in nude mice to study the association of Nrf2 with differentiation in vivo. The expression of Nrf2 decreased with the differentiation process. Following Nrf2 knockdown, the proportion of sphere-like colonies decreased and the dendritic cells in spheres increased; the expression of Nrf2 significantly decreased while the expression of differentiation marker glial fibrillary acidic protein (GFAP) and ßIII-tubulin increased both at the protein and the gene level. In the xenografts of nude mice, the differentiation of tumor cells was improved. These results suggest that Nrf2 is a key factor inhibiting the differentiation of GSCs, and knockdown of Nrf2 may promote the differentiation process, providing a therapy target for GSCs.

Targeting the NF-E2-related factor 2 pathway: a novel strategy for glioblastoma (review).

Glioblastoma is the most common and malignant subtype among all brain tumors. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential component of cellular defense against a variety of endogenous and exogenous stresses. A marked increase in research over the past few decades focusing on Nrf2 and its role in regulating glioblastoma has revealed the potential value of Nrf2 in the treatment of glioblastoma. In the present review, we discuss a novel framework of Nrf2 in the regulation of glioblastoma and the mechanisms regarding the downregulation of Nrf2 in treating glioblastoma. The candidate mechanisms include direct and indirect means. Direct mechanisms target tumor molecular pathways in order to overcome resistance to chemotherapy and radiotherapy, to inhibit proliferation, to block invasion and migration, to induce apoptosis, to promote differentiation, to enhance autophagy and to target glioblastoma stem cells. Indirect mechanisms target the reaction between glioblastoma cells and the surrounding microenvironment. Overall, the value of the Nrf2 pathway in glioblastoma provides a promising opportunity for new approaches by which to treat glioblastoma.