NRF1 Alleviated Oxidative Stress of Glioblastoma Cells by Regulating NOR1.

Oxidored-nitro domain-containing protein 1 (NOR1) is a critical tumour suppressor gene, though its regulatory mechanism in oxidative stress of glioblastoma (GBM) remains unclear. Hence, further study is needed to unravel the function of NOR1 in the progression of oxidative stress in GBM. In this study, we evaluated the expression of NOR1 and nuclear respiratory factor 1 (NRF1) in GBM tissue and normal brain tissue (NBT) using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB), and investigated their relationship. We then induced oxidative stress in U251 cells through H2O2 treatment and conducted Cell Count-ing Kit-8, Transwell and wound healing assays to analyse cell proliferation, invasion and migration. Cell apoptosis was assessed by flow cytometry and TUNEL staining. We also measured the activities of superoxide dismutase and catalase, as well as the level of reactive oxygen species (ROS) using biochemical techniques. Via qRT-PCR and WB, the mRNA and protein expression levels of NOR1 and NRF1 were determined. Chromatin immunoprecipitation (ChIP) assays were applied to validate NRF1's interaction with NOR1. Our results showed that the expression of NOR1 and NRF1 was low in GBM, and their expression levels were positively correlated. H2O2-induced oxidative stress reduced NRF1 and NOR1 expression levels and increased the ROS level. The ChIP assay confirmed the binding of NRF1 to NOR1. Over-expression of NRF1 attenuated the inhibitory effect of oxidative stress on the proliferation, migration and invasion of U251 cells, which was reversed by knockdown of NOR1.

Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1.

Glioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim of the present study was to examine the pathogenesis and potential molecular markers of glioma by comparing the differential expression of miRNA and mRNA between glioma tissue and peritumor brain tissue. We explored the impact of screened core miRNA and mRNA on cell proliferation, invasion, and migration of glioma. An miRNA expression profile dataset (GSE90603) and a transcriptome profile dataset (GSE90598) were downloaded from combined miRNA-mRNA microarray chips in the Gene Expression Omnibus (GEO) database. Overall, 59 differentially expressed miRNAs (DEMs) and 419 differentially expressed genes (DEGs) were identified using the R limma software package. FunRich software was used to predict DEM target genes and miRNA-gene pairs, and Perl software was used to find overlapping genes between DEGs and DEM target genes. There were 129 overlapping genes regulated by nine miRNAs between target genes of the DEMs and DEGs. The Chinese Glioma Genome Atlas(CGGA) was analyzed in order to identify miRNAs with diagnostic and prognostic significance. MiR-139-5p, miR-137, and miR-338-3p were validated to be significantly linked to prognosis in glioma patients. Finally, we validated that miR-139-5p affected glioma malignant biological behavior via targeting gamma-aminobutyric acid A receptor alpha 1(GABRA1) through rescue experiments. Low miR-139-5p expression was correlated with survival probability and World Health Organization (WHO) grade. MiR-139-5p overexpression inhibited cell proliferation, migration, and invasion of glioma in vitro. GABRA1 was identified as a functional downstream target of miR-139-5p. Decreased GABRA1 expression was related to similar biological roles as miR-139-5p overexpression while upregulation of GABRA1 effectively reversed the inhibition effects of miR-139-5p. These results demonstrate a novel axis for miR-139-5p/GABRA1 in glioma progression and provide potential prognostic predictors and therapeutic target for glioma patients.

Treatment of hard-to-heal wound after huge scalp tumor resection and reconstruction: a case report.

Introduction and importance: Free skin flap transplantation and titanium mesh reconstruction can effectively repair the scalp and skull defects caused by massive scalp tumour resection. Postoperative flap infection is a common complication. Due to the presence of titanium mesh, once infection occurs, a second operation is required to remove the titanium mesh, which brings a great physical and economic burden to the patient. Case presentation: In this case of postoperative infection, the authors used a conservative treatment based on dressing change, preserved the titanium mesh and flap, avoided secondary surgery, and successfully controlled the infection. Clinical discussion: The treatment strategy is mainly divided into three steps: the first stage is to control infection, the authors use complexed iodine to repeatedly disinfect wounds, subcutaneous dead space, exposed titanium mesh, and antibiotic treatment for bacterial culture results; the second stage is to promote granulation growth, After infection control, the authors remove old granulation after each wound disinfection, and then instill fibroblast growth factor to promote subcutaneous granulation growth to fill dead space, and also provide a base platform for epidermal growth; the third stage is mainly epidermal healing, Change the dressing every day to observe the growth of the epidermis. Conclusion: This case suggests that conservative treatment strategy based on dressing change is also a potential treatment option for postoperative infection of the flap with exposure of the titanium plate.

miR-138-5p Inhibits the Growth and Invasion of Glioma Cells by Regulating WEE1.

BACKGROUND: Accumulating evidence has demonstrated the role of differentially expressed miRNAs in glioma progression. Our previous bioinformatics analyses revealed a role of miR-138-5p in glioma. miR-138-5p was decreased in various tumors, and He et al. found that miR-138-5p had an inhibitory effect on glioma cells in 2021. However, the role of miR-138-5p in the development of glioma and the underlying mechanism is unknown. In this study, we explored whether miR-138-5p affects the biology of glioma by regulating WEE1 expression. METHODS: miR-138-5p and WEE1 G2 checkpoint kinase (WEE1) RNA and protein expression levels in glioma tissues were detected with qRT-PCR and western blotting, respectively. The effects of miR-138-5p and WEE1 on glioma cell migration and invasion were investigated using Transwell assays. CCK-8 assay was used to measure the effects of miR-138-5p and WEE1 on glioma cell proliferation. The mortality of glioma cells transfected with miR-138-5p and WEE1 was measured with flow cytometry. The relationship between miR-138-5p and WEE1 was explored using a luciferase reporter analysis. RESULTS: Functional studies indicated that overexpression of miR-138-5p suppressed cell proliferation, migration, and invasion and promoted death in glioma cell lines. WEE1 was identified as a target of miR-138-5p, and overexpression of miR-138-5p significantly suppressed the levels of WEE1. Moreover, reintroduction of WEE1 partially abrogated miR-138-5p-induced suppression of motility and invasion in glioma cells. CONCLUSION: The low expression of miR-138-5p in glioma suggests a tumor suppressor role for this miRNA. miR-138-5p suppresses glioma progression by regulating WEE1. These data provide new insights into the molecular mechanism of glioma.

Genomic comparison between cerebrospinal fluid and primary tumor revealed the genetic events associated with brain metastasis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is most common pathological type of lung cancer. LUAD with brain metastases (BMs) usually have poor prognosis. To identify the potential genetic factors associated with BM, a genomic comparison for BM cerebrospinal fluid (CSF) and primary lung tumor samples obtained from 1082 early- and late-stage LUAD patients was performed. We found that single nucleotide variation (SNV) of EGFR was highly enriched in CSF (87% of samples). Compared with the other primary lung tissues, copy number gain of EGFR (27%), CDK4 (11%), PMS2 (11%), MET (10%), IL7R (8%), RICTOR (7%), FLT4 (5%), and FGFR4 (4%), and copy number loss of CDKN2A (28%) and CDKN2B (18%) were remarkably more frequent in CSF samples. CSF had significantly lower tumor mutation burden (TMB) level but more abundant copy number variant. It was also found that the relationships among co-occurrent and mutually exclusive genes were dynamically changing with LUAD development. Additionally, CSF (97% of samples) harbored more abundant targeted drugs related driver and fusion genes. The signature 15 associated with defective DNA mismatch repair (dMMR) was only identified in the CSF group. Cancer associated pathway analysis further revealed that ErbB (95%) and cell cycle (84%) were unique pathways in CSF samples. The tumor evolution analysis showed that CSF carried significantly fewer clusters, but subclonal proportion of EGFR was remarkably increased with tumor progression. Collectively, CSF sequencing showed unique genomic characteristics and the intense copy number instability associated with cell cycle disorder and dMMR might be the crucial genetic factors in BM of LUAD.

Exploring the efficacy of tumor electric field therapy against glioblastoma: An in vivo and in vitro study.

AIMS: Tumor electric fields therapy (TTFields) is emerging as a novel anti-cancer physiotherapy. Despite recent breakthroughs of TTFields in glioma treatment, the average survival time for glioblastoma patients with TTFields is <2 years, even when used in conjugation with traditional anti-cancer therapies. To optimize TTFields-afforded efficacy against glioblastoma, we investigated the cancer cell-killing effects of various TTFields paradigms using in vitro and in vivo models of glioblastoma. METHODS: For in vitro studies, the U251 glioma cell line or primary cell cultures prepared from 20 glioblastoma patients were treated with the tumor electric field treatment (TEFT) system. Cell number, volume, and proliferation were measured after TEFT at different frequencies (100, 150, 180, 200, or 220 kHz), durations (24, 48, or 72 h), field strengths (1.0, 1.5, or 2.2V/cm), and output modes (fixed or random sequence output). A transwell system was used to evaluate the influence of TEFT on the invasiveness of primary glioblastoma cells. For in vivo studies, the therapeutic effect and safety profiles of random sequence electric field therapy in glioblastoma-transplanted rats were assessed by calculating tumor size and survival time and evaluating peripheral immunobiological and blood parameters, respectively. RESULTS: In the in vitro settings, TEFT was robustly effective in suppressing cell proliferation of both the U251 glioma cell line and primary glioblastoma cell cultures. The anti-proliferation effects of TEFT were frequency- and "dose" (field strength and duration)-dependent, and contingent on the field sequence output mode, with the random sequence mode (TEFT-R) being more effective than the fixed sequence mode (TEFT-F). Genetic tests were performed in 11 of 20 primary glioblastoma cultures, and 6 different genetic traits were identified them. However, TEFT exhibited comparable anti-proliferation effects in all primary cultures regardless of their genetic traits. TEFT also inhibited the invasiveness of primary glioblastoma cells in transwell experiments. In the in vivo rat model of glioblastoma brain transplantation, treatment with TEFT-F or TEFT-R at frequency of 200 kHz and field strength of 2.2V/cm for 14 days significantly reduced tumor volume by 42.63% (TEFT-F vs. control, p = 0.0002) and 63.60% (TEFT-R vs. control, p < 0.0001), and prolonged animal survival time by 30.15% (TEFT-F vs. control, p = 0.0415) and 69.85% (TEFT-R vs. control, p = 0.0064), respectively. The tumor-bearing rats appeared to be well tolerable to TEFT therapies, showing only moderate increases in blood levels of creatine and red blood cells. Adverse skin reactions were common for TEFT-treated rats; however, skin reactions were curable by local treatment. CONCLUSION: Tumor electric field treatment at optimal frequency, strength, and output mode markedly inhibits the cell viability, proliferation, and invasiveness of primary glioblastoma cells in vitro independent of different genetic traits of the cells. Moreover, a random sequence electric field output confers considerable anti-cancer effects against glioblastoma in vivo. Thus, TTFields are a promising physiotherapy for glioblastoma and warrants further investigation.

The biological and diagnostic roles of MicroRNAs in meningiomas.

MicroRNAs (miRNAs) refer to a class of small endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level. Emerging studies have shown that miRNAs play critical roles in tumorigenesis and cancer progression. However, roles and mechanisms of miRNA dysregulation in the pathogenesis of meningioma are not fully understood. Here, we first reviewed existing research of aberrantly expressed miRNAs identified by high throughput microarray profiling in meningioma. We also explored the potential of miRNA as biomarkers and therapeutic targets for novel treatment paradigms of meningiomas. In addition, we summarized recent researches that focused on the possible mechanisms involved in miRNA-mediate meningioma occurrence and progression. This review provides an overview of miRNA deregulation in meningioma and indicates the potential of miRNAs to be used as biomarkers or novel therapeutic targets.

Solitary plasmacytoma of the occipital bone: a case report.

Solitary plasmacytoma (SP) of the skull is an uncommon clinical entity that is characterized by a localized proliferation of neoplastic monoclonal plasma cells. This case report describes a 50-year-old male that presented with a headache and an exophytic soft mass on the occiput. The diagnosis of SP was based on the pathological results and imaging examinations. The patient underwent occipital craniotomy, skull reconstruction and lower trapezius myocutaneous flap (LTMF) transplantation under general anaesthesia. The tumour was capsulized and extended to the subcutaneous and the subdural space through the dura mater with skull defects. The neoplasm of the occipital bone involved large areas of scalp and subcutaneous tissue, which resulted in a large postoperative scalp defect that was repaired using LTMF transplantation. All of the tumour was removed and the transplanted flap grew well. Follow-up at 5 months identified an aggressive mass lesion on the right frontal lobe. The patient received six cycles of the PAD chemotherapy regimen (bortezomib, doxorubicin and dexamethasone) and the lesion was significantly reduced. This case demonstrates that LTMF is an alternative approach for the repair of scalp and subcutaneous soft tissue defects caused by the excision of a large malignant tumour of the occipital region. Chemotherapy is the choice of treatment for neoplastic recurrence.