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Background: Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve tissue. Honokiol is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae plants. It also has anti-infection, antitumor, and immunomodulatory effects. In this study, we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and U251-MG. However, the mechanism through which honokiol regulates glioma cell apoptosis is still unknown. Methods: We performed RNAseq analysis of U251-MG cells treated with honokiol and control cells. Protein-protein interaction (PPI) network analysis was performed, and the 10 top hub unigenes were examined via real-time quantitative PCR. Furthermore, MAPK signaling and ferroptosis were detected via western blotting. Results: 332 differentially expressed genes (DEGs) were found, comprising 163 increased and 169 decreased genes. Analysis of the DEGs revealed that various biological processes were enriched, including 'response to hypoxia', 'cerebellum development cellular response to hypoxia,' 'iron ion binding,' 'oxygen transporter activity,' 'oxygen binding,' 'ferric iron binding,' and 'structural constituent of cytoskeleton.' Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs were enriched in the following pathways: 'mitogen-activated protein kinases (MAPK)', 'Hypoxia-inducible factor 1 (HIF-1)', 'ferroptosis,' 'Peroxisome proliferator-activated receptor (PPAR),' 'Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)- protein kinase B (Akt),' and 'phagosome.' Among these pathways, the MAPK signaling pathway and ferroptosis were verified. Conclusion: This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling pathways. These data could lead to new ideas for future research and therapy for patients with glioma. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between isocitrate dehydrogenase (IDH) 1/2 mutation, telomerase reverse transcriptase (TERT) gene promoter mutation and the prognosis of human glioma patients. Methods: One hundred fifteen patients with human glioma, treated surgically in The First Affiliated Hospital of Hebei North University from January 2019 to January 2020, were included. All patients were followed up until January 31, 2022. The mutations of IDH1/2 and TERT promoter were analyzed, and risk factors affecting survival of the patients with glioma were assessed. Results: IDH1 gene mutation occurred in 82 cases, IDH2 gene mutation occurred in five cases and TERT promoter mutation occurred in 54 cases. Univariate analysis showed that tumor WHO grade, resection range, preoperative Karnofsky performance status score, postoperative radiotherapy and chemotherapy, IDH1/2 gene and TERT promoter mutation influenced postoperative survival of patients with glioma (P<0.05). Kaplan-Meier survival curve showed that IDH1/2 gene and TERT promoter mutation were significantly different from those of wild-type patients (P<0.05). Conclusion: IDH1/2 gene and TERT promoter mutations are more frequent in patients with human glioma. These related factors can be used as molecular markers to aid in the prognosis of patients with glioma. [ABSTRACT FROM AUTHOR]

Introduction: copaifera is a genus of plants that comprises several species that produce copaiba oil, which is widely used for various purposes, such as healing, antiinflammatory, antimicrobial, wound antiseptic, anti-tumor, among other functions. There are very few chemical studies to characterize copaiba oil. Aim: To characterize 3 different species of copaiba oil Subsequently, the effects of oils were estimated on neoplastic cells in a human glioma protocol (U251). Methods: 2 methods of analysis were used for the chemical characterization, GC-MS and ESI-MS. Results: Through these analytical techniques, 20 types of components were found in the oils. Obtaining the cell viability and cytotoxicity of the oil we performed two methods, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Neutral Red (NR), both assays were quantified by spectrophotometry. Concentrations of 1 to 10-5 µg/mL were used for 3 different species of copaiba oil and doxorubicin hydrochloride was used as a positive control. The 3 different species of copaiba oil from Pernambuco (oil 1) and Manaus (oils 2 and 3) were cytotoxic in U251, the IC50 value obtained was 6.171·10-2 μg/mL, 8.344·10-2 μg/mL and 1.385·10-4 μg/mL, respectively. They also presented cytotoxic effect, with IC50, 2.4·10-1 μg/mL, 3.7·10-2 μg/mL and 4.6·10-2 µg/mL, respectively. A high correlation was evidenced between the MTT and Neutral Red studies for the three different species of copaiba oil, with α=0.05 and r values above 0.9, using the Pearson correlation coefficient. All types of resin oils positively affected cell proliferation of in vitro studies with a correspondence between concentration and effect. [ABSTRACT FROM AUTHOR]

Gliomas are considered one of the most malignant tumors in the body. The immune system has the ability to control the initiation and development of tumors, including gliomas. Thus, immune cells find themselves controlled by various molecular pathways, inhibiting their activation, such as the immunosuppressive adenosine 2A receptor (A2AR). Our objective was to establish the expression profile and role of A2AR at the transcriptomic level, using real-time RT-PCR in Moroccan glioma patients, in addition to TCGA and CGGA cohorts. The real-time RT-PCR results in Moroccan patients showed that high expression of this gene was associated with poor survival in males. Our study on the CGGA cohort corroborated these results. In addition, there was a positive association of A2AR with T-cell exhaustion genes. A2AR also correlated strongly with genes that are primarily enriched in focal adhesion and extracellular matrix interactions, inducing epithelial mesenchymal transition, angiogenesis, and glioma growth. However, in the TCGA cohort, the A2AR showed results that were different from the two previously examined cohorts. In fact, this gene was instead linked to a good prognosis in patients with the astrocytoma histological type. The correlation and enrichment results reinforced the prognostic role of A2AR in this TCGA cohort, in which its high expression was shown to be related to lymphocyte differentiation and a successful cytolytic response, suggesting a more efficient anti-tumor immune response. Correlations and differential analyses based on A2AR gene expression, to understand the cause of the association of this gene with two different prognoses (CGGA males and TCGA Astrocytoma), showed that the overexpression of A2AR in Chinese male patients could be associated with the overexpression of extracellular adenosine, which binds to A2AR to induce immunosuppression and consequently a poor prognosis. However, in the second group (TCGA astrocytomas), the overexpression of the gene could be associated with an adenosine deficiency, and therefore this receptor does not undergo activation. The absence of A2AR activation in these patients may have protected them from immunosuppression, which could reflect the good prognosis. A2AR can be considered a promising therapeutic target in male CGGA and Moroccan patients with gliomas. [ABSTRACT FROM AUTHOR]

Zixi Yang,1 Feng Ling,1 Sibei Ruan,1 Jiajia Hu,2 Mingxi Tang,1 Xingwang Sun,1 Wenbo Long1 1Pathology Department of the First Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Wenbo Long Email wenbolong@swmu.edu.cnBackground and Objective: Genetic alterations, including IDH, BRAF, and TERT promoter mutations (IDH-mu, BRAF-mu, TERTp-mu, respectively), 1p/19q co-deletion (1p/19q-codel), and MGMT promoter methylation (MGMTp-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diagnosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood.Methods: We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II–IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry.Results: In the 103 cases, MGMTp-M was the most common alteration (70.9%), followed by TERTp-mu (58.3%), IDH-mu (46.6%), 1p/19q-codel (34.0%), and BRAF-mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (IDH-mu/TERTp-mu/MGMTp-M/1p/19q-codel). The percentage of TERTp-mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of IDH-mu and 1p/19q-codel cases decreased with Ki-67 expression. IDH-mu, MGMTp-M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while TERTp-mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, IDH-mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis.Conclusion: IDH-mu only and quadruple-positivity were associated with good OS in glioma patients, while TERTp-mu only, TERTp-mu/MGMTp-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.Keywords: human glioma, biomarker, correlation analysis, genetic alteration, survival rate

Gliomas are considered one of the most malignant tumors in the body. The immune system has the ability to control the initiation and development of tumors, including gliomas. Thus, immune cells find themselves controlled by various molecular pathways, inhibiting their activation, such as the immunosuppressive adenosine 2A receptor (A2AR). Our objective was to establish the expression profile and role of A2AR at the transcriptomic level, using real-time RT-PCR in Moroccan glioma patients, in addition to TCGA and CGGA cohorts. The real-time RT-PCR results in Moroccan patients showed that high expression of this gene was associated with poor survival in males. Our study on the CGGA cohort corroborated these results. In addition, there was a positive association of A2AR with T-cell exhaustion genes. A2AR also correlated strongly with genes that are primarily enriched in focal adhesion and extracellular matrix interactions, inducing epithelial mesenchymal transition, angiogenesis, and glioma growth. However, in the TCGA cohort, the A2AR showed results that were different from the two previously examined cohorts. In fact, this gene was instead linked to a good prognosis in patients with the astrocytoma histological type. The correlation and enrichment results reinforced the prognostic role of A2AR in this TCGA cohort, in which its high expression was shown to be related to lymphocyte differentiation and a successful cytolytic response, suggesting a more efficient anti-tumor immune response. Correlations and differential analyses based on A2AR gene expression, to understand the cause of the association of this gene with two different prognoses (CGGA males and TCGA Astrocytoma), showed that the overexpression of A2AR in Chinese male patients could be associated with the overexpression of extracellular adenosine, which binds to A2AR to induce immunosuppression and consequently a poor prognosis. However, in the second group (TCGA astrocytomas), the overexpression of the gene could be associated with an adenosine deficiency, and therefore this receptor does not undergo activation. The absence of A2AR activation in these patients may have protected them from immunosuppression, which could reflect the good prognosis. A2AR can be considered a promising therapeutic target in male CGGA and Moroccan patients with gliomas.

Gambogic acid (GA) is a highly effective antitumor agent, and it is used for the treatment of a wide range of cancers. It is challenging to deliver drugs to the central nervous system due to the inability of GA to cross the blood–brain barrier (BBB). Studies have shown that ultrasound-targeted microbubble destruction can be used for transient and reversible BBB disruption, significantly facilitating intracerebral drug delivery. We first prepared GA–loaded porous-lipid microbubbles (GA porous-lipid/PLGA MBs), and an in vitro BBB model was established. The cell viability was detected by CCK-8 assay and flow cytometry. The results indicate that U251 human glioma cells were killed by focused ultrasound (FUS) combined with GA/PLGA microbubbles. FUS combined with GA/PLGA microbubbles was capable of locally and transiently enhancing the permeability of BBB under certain conditions. This conformational change allows the release of GA to extracellular space. This study provides novel targets for the treatment of glioma.

Plasmacytoma variability translocation 1 (PVT1), an oncogene, has been reported to be highly expressed in many tumors, including human glioma, gastric cancer, and non-small cell lung cancer. Functionally, it could also regulate the development of tumor cells. However, its specific roles and pathogenesis in human gliomas are still not clear. This study investigated the function and mechanism of PVT1 knockdown in the proliferation and malignant transformation of human gliomas. We first examined the expression levels of PVT1 and miR- 424 in human glioma tissues and cell lines. We also used gene manipulation techniques to explore the effects of PVT1 knockdown on cell viability, migration, invasion, and miR-424. We found that PVT1 knockdown effectively inhibited cell viability, migration, and invasion of human glioma cells and increased miR-424 expression. Based on the negative correlation between PVT1 and miR-424, we then confirmed the direct interaction between PVT1 and miR-424 using RNA immunoprecipitation (RIP) and luciferase reporter assays. Further, we established a xenograft nude mouse model to determine the role and mechanism of PVT1 on tumor growth in vivo. In addition, PVT1 knockdown was shown to promote miR-424 in vivo. In summary, the present study demonstrated that PVT1 knockdown could negatively regulate miR-424 to inhibit human glioma cell activity, migration, and invasiveness. PVT1 knockdown could negatively regulate miR-424 to inhibit cellular activity, migration, and invasiveness in human gliomas, which explained the oncogenic mechanism of PVT1 in human gliomas. It also suggested that PVT1 might be a novel therapeutic target for human gliomas. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the location, expression and clinical significance of Iroquois homeobox gene (IRX1) in human glioma. The expression of IRX1 gene in glioma cell lines (U87, U373, LN229 and T98G) and normal brain tissue was detected via reverse transcription-polymerase chain reaction. The IRX1 protein in fresh glioma specimens, with the adjacent normal brain tissue, was quantified through western blotting. The archived glioma only specimens from the present hospital and glioma specimens with adjacent normal brain tissue, from Alenabio biotechnology, were subjected to immunohistochemistry and tissue microarray analysis, respectively. The Kaplan-Meier method was employed to assess the correlation between the IRX1 level and the overall survival time of the patients. IRX1 gene was demonstrated to be expressed at varying levels in U373, LN229 and T98G cells, however not in U87 cells and normal brain tissue. Western blotting revealed increased IRX1 expression in glioma tissue compared with adjacent normal brain tissue. Furthermore, a direct correlation was observed between the IRX1 expression and the clinical glioma grade, with a significant difference in the gene expression between high grade and low grade glioma (P<0.05). Notably, IRX1 was identified to be localized to the cytoplasm in the adjacent normal brain and World Health Organization grade I glioma, whereas was identified to be present in the nucleus in higher grade glioma. In addition to being established as a significant prognostic variable, IRX1 expression was positively correlated with the overall survival of glioma patients. IRX1 gene may therefore exhibit an oncogenic role in glioma condition, and thus may be of clinical importance as a future therapeutic target. [ABSTRACT FROM AUTHOR]

Several known sesquiterpenoid quinones and quinols (1−9), and kauamide (10), a new polyketide-peptide containing an 11-membered heterocycle, were isolated from the extracts of the Hawaiian marine sponge Dactylospongia elegans. The planar structure of 10 was determined from spectroscopic analyses, and its relative and absolute configurations were established from density functional theory (DFT) calculations of the GIAO NMR shielding tensors, and advanced Marfey’s analysis of the N-MeLeu residue, respectively. Compounds 1 and 3 showed moderate inhibition of β-secretase 1 (BACE1), whereas 1−9 exhibited moderate to potent inhibition of growth of human glioma (U251) cells. Compounds 1−2 and 4−7 were also active against human pancreatic carcinoma (Panc-1) cells.

The present study aimed to investigate the associations of tumor inhibitor of growth 4 (ING4) with tumor cell proliferation and microvessel density (MVD) in human glioma. Semi-quantitative reverse transcription polymerase chain reaction, western blotting and immunohistochemistry (IHC) were used to detect the level of ING4 expression in normal brain tissues and glioma tissues of different pathological grades. The cell proliferation index (PI) and the level of MVD were detected using IHC, facilitating the analysis of the correlation between ING4 and cellular proliferation and MVD in human glioma. The expression levels of ING4 mRNA and protein were significantly lower in the glioma tissues compared with the normal brain tissues (P<0.05) and decreased as the pathological grade of the glioma tissue increased (P<0.05). PI was reduced in the ING4 protein positively expressed (ING4+) glioma tissues compared with the ING4 protein negatively expressed (ING4-) glioma tissues (P=0.01). The level of MVD was significantly higher in the glioma tissues than that in the normal brain tissues (P=0.01), while the level of MVD decreased in the ING4+ glioma tissue compared with the ING4- glioma tissue (P=0.001). A Spearman's rank correlation test revealed that ING4 protein expression was negatively correlated with PI and MVD. ING4 might inhibit tumor proliferation and angiogenesis in human glioma. The expression of ING4 was also associated with the pathological grading of the glioma tissue and negatively correlated with cellular proliferation and MVD in human glioma. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression and clinical significance of Iroquois homeobox gene IRX1 in human glioma. Methods: 4 groups of glioma tissues and adjacent normal brain tissues form the same patient were collected, respectively. Another 54 glioma tissue samples were prepared too, of which 21 were classified as low-grade [5 pilocytic astrocytomas (WHO I) and 16 diffuse astrocytomas (WHO II)] and 33 were classified as high-grade gliomas [14 anaplasia astrocytomas (WHO III) and 19 primary glioblastomas (WHO IV)]. The expression of IRX1 gene in glioma cells (U87, U373, LN229 and T98G) was detected by PCR. And the expression of IRX1 protein in glioma tissues was verified by western blot and IHC. Results: IRX1 gene was expressed in U373, LN229 and T98G cells, but no expression in U87 cells and adjacent normal brain tissues. Furthermore, the results of western blot and IHC showed that the expression levels of IRX1 protein was higher in glioma tissues than in normal tissues (P＜0.05), and a high level of IRX1 expression was significantly more common in glioma tissues of more advanced grade than those of lower grade (P＜0.05). Conclusion: IRX1 might involve in the regulation of onset and progress of glioma, of which the expression was related to the grade of carcinoma, indicating that IRX1 might be used as an indicator for evaluation of prognosis and malignancy level as well as targeted molecular therapy of human malignant glioma. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between isocitrate dehydrogenase (IDH) 1/2 mutation, telomerase reverse transcriptase (TERT) gene promoter mutation and the prognosis of human glioma patients., Methods: One hundred fifteen patients with human glioma, treated surgically in The First Affiliated Hospital of Hebei North University from January 2019 to January 2020, were included. All patients were followed up until January 31, 2022. The mutations of IDH1/2 and TERT promoter were analyzed, and risk factors affecting survival of the patients with glioma were assessed., Results: IDH1 gene mutation occurred in 82 cases, IDH2 gene mutation occurred in five cases and TERT promoter mutation occurred in 54 cases. Univariate analysis showed that tumor WHO grade, resection range, preoperative Karnofsky performance status score, postoperative radiotherapy and chemotherapy, IDH1/2 gene and TERT promoter mutation influenced postoperative survival of patients with glioma (P<0.05). Kaplan-Meier survival curve showed that IDH1/2 gene and TERT promoter mutation were significantly different from those of wild-type patients (P<0.05)., Conclusion: IDH1/2 gene and TERT promoter mutations are more frequent in patients with human glioma. These related factors can be used as molecular markers to aid in the prognosis of patients with glioma., (Copyright: © Pakistan Journal of Medical Sciences.)

Our previous findings performed in rat tissues demonstrated that intermediate filament nestin is expressed in endothelial cells of newly formed blood vessels of developing organs and neural transplants. The aim of the present study was to identify other cellular markers expressed in nestin-positive (nestin+) blood vessels. To reach this goal we performed double immunofluorescent study to co-localize nestin with endothelium-specific markers (CD31, CD34 II, vimentin) or markers of perivascular cells (GFAP, SMA) in paraffin-embedded sections of normal human brain tissue, low- and high-grade gliomas, postinfarcted heart and samples of non-neural tumours. Our findings documented that all the samples examined contained blood vessels with different ratio of nestin+ endothelial cells. Double immunostaining provided unambiguous evidence that endothelial cells expressed nestin and allowed them to distinguish from other nestin+ elements (perivascular astrocytic endfeet, undifferentiated tumour cells, smooth muscle cells and pericytes). Nestin+ endothelium was not confined only to newly formed capillaries but was also observed in blood vessels of larger calibres, frequently in arterioles and venules. We conclude that nestin represents a reliable vascular marker that is expressed in endothelial cells. Elevation of nestin expression likely corresponds to reorganization of intermediate filament network in the cytoskeleton of endothelial cells in the course of their maturation or adaptation to changes in growing tissues.