Non-apoptotic regulated cell death mediates reprogramming of the tumour immune microenvironment by macrophages.

Tumour immune microenvironment (TIME) plays an indispensable role in tumour progression, and tumour-associated macrophages (TAMs) are the most abundant immune cells in TIME. Non-apoptotic regulated cell death (RCD) can avoid the influence of tumour apoptosis resistance on anti-tumour immune response. Specifically, autophagy, ferroptosis, pyroptosis and necroptosis mediate the crosstalk between TAMs and tumour cells in TIME, thus reprogram TIME and affect the progress of tumour. In addition, although some achievements have been made in immune checkpoint inhibitors (ICIs), there is still defect that ICIs are only effective for some people because non-apoptotic RCD can bypass the apoptosis resistance of tumour. As a result, ICIs combined with targeting non-apoptotic RCD may be a promising solution. In this paper, the basic molecular mechanism of non-apoptotic RCD, the way in which non-apoptotic RCD mediates crosstalk between TAMs and tumour cells to reprogram TIME, and the latest research progress in targeting non-apoptotic RCD and ICIs are reviewed.

Carbon quantum dots of ginsenoside Rb1 for application in a mouse model of intracerebral Hemorrhage.

After intracerebral hemorrhage (ICH) occurs, the overproduction of reactive oxygen species (ROS) and iron ion overload are the leading causes of secondary damage. Removing excess iron ions and ROS in the meningeal system can effectively alleviate the secondary damage after ICH. This study synthesized ginsenoside Rb1 carbon quantum dots (RBCQDs) using ginsenoside Rb1 and ethylenediamine via a hydrothermal method. RBCQDs exhibit potent capabilities in scavenging ABTS + free radicals and iron ions in solution. After intrathecal injection, the distribution of RBCQDs is predominantly localized in the subarachnoid space. RBCQDs can eliminate ROS and chelate iron ions within the meningeal system. Treatment with RBCQDs significantly improves blood flow in the meningeal system, effectively protecting dying neurons, improving neurological function, and providing a new therapeutic approach for the clinical treatment of ICH.

Deep learning-assisted identification and quantification of aneurysmal subarachnoid hemorrhage in non-contrast CT scans: Development and external validation of Hybrid 2D/3D UNet.

Accurate stroke assessment and consequent favorable clinical outcomes rely on the early identification and quantification of aneurysmal subarachnoid hemorrhage (aSAH) in non-contrast computed tomography (NCCT) images. However, hemorrhagic lesions can be complex and difficult to distinguish manually. To solve these problems, here we propose a novel Hybrid 2D/3D UNet deep-learning framework for automatic aSAH identification and quantification in NCCT images. We evaluated 1824 consecutive patients admitted with aSAH to four hospitals in China between June 2018 and May 2022. Accuracy and precision, Dice scores and intersection over union (IoU), and interclass correlation coefficients (ICC) were calculated to assess model performance, segmentation performance, and correlations between automatic and manual segmentation, respectively. A total of 1355 patients with aSAH were enrolled: 931, 101, 179, and 144 in four datasets, of whom 326 were scanned with Siemens, 640 with Philips, and 389 with GE Medical Systems scanners. Our proposed deep-learning method accurately identified (accuracies 0.993-0.999) and segmented (Dice scores 0.550-0.897) hemorrhage in both the internal and external datasets, even combinations of hemorrhage subtypes. We further developed a convenient AI-assisted platform based on our algorithm to assist clinical workflows, whose performance was comparable to manual measurements by experienced neurosurgeons (ICCs 0.815-0.957) but with greater efficiency and reduced cost. While this tool has not yet been prospectively tested in clinical practice, our innovative hybrid network algorithm and platform can accurately identify and quantify aSAH, paving the way for fast and cheap NCCT interpretation and a reliable AI-based approach to expedite clinical decision-making for aSAH patients.

Pan-cancer analysis: predictive role of TAP1 in cancer prognosis and response to immunotherapy.

BACKGROUND: Transporter associated with antigen processing 1 (TAP1) is a molecule involved in processing and presentation of major histocompatibility complex class I restricted antigens, including tumor-associated antigens. TAP1 participates in tumor immunity, and is aberrantly expressed in multiple cancer types; METHODS: Transcriptome profiles were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Genetic alterations, protein distribution, and interaction information for TAP1 were downloaded from cBioPortal, Human Protein Atlas and Compartmentalized Protein-Protein Interaction, respectively. Single-cell analyses of TAP1 across cancers were conducted via the Tumor Immune Single-cell Hub website. Gene set enrichment analysis was employed to investigate TAP1-associated functional mechanisms and processes. Immune cell infiltration was explored using Tumor Immune Estimation Resource 2.0. Pan-cancer correlations between TAP1 expression and immunotherapy biomarkers were explored using the Spearman's correlation test. Associations with immunotherapy responses were also investigated using clinicopathological and prognostic information from cohorts of patients with cancer receiving immune checkpoint inhibitors. RESULTS: TAP1 expression was elevated in most cancer types and exhibited distinct prognostic value. Immune cells expressed more TAP1 than malignant cells within most tumors. TAP1 expression was significantly correlated with immune-related pathways, T-lymphocyte infiltration, and immunotherapeutic biomarkers. Clinical cohort validation revealed a significant correlation with immune therapeutic effects and verified the prognostic role of TAP1 in immunotherapy. Western blot assay indicated that TAP1 is upregulated in glioblastoma compared with adjacent normal brain tissues. CONCLUSION: TAP1 is a robust tumor prognostic biomarker and a novel predictor of clinical prognosis and immunotherapeutic responses in various cancer types.

Randomized, prospective, multicenter trial assessing the numen coil embolization system in the endovascular treatment of small intracranial aneurysms: outcomes from the CATCH Trial.

BACKGROUND AND PURPOSE: The CATCH (Coil Application Trial in China) trial was designed to assess the safety and efficacy of the Numen Coil Embolization System in the treatment of intracranial aneurysms in comparison with the Axium coil (ev3/Medtronic). Although the endovascular treatment of small (< 5 mm) intracranial aneurysms has been reported with favorable long-term clinical and angiographic outcomes, randomized trials are still lacking. Data for aneurysms smaller than 5 mm were extracted from the CATCH trial. MATERIALS AND METHODS: A randomized, prospective, multicenter trial was conducted at ten centers throughout China. Enrolled subjects with small intracranial aneurysms were randomly assigned to receive treatment with the Numen Coil or the Axium coil. The primary outcome was successful aneurysm occlusion at the 6-month follow-up. In contrast, the secondary outcomes included complete aneurysm occlusion, recurrence rate, clinical deterioration, and safety data at the 6-month and 12-month follow-ups. RESULTS: A total of 124 patients were enrolled in the study. Overall, 58 patients were assigned to the Numen group, and 66 were assigned to the Axium group. At the 6-month follow-up, the successful aneurysm occlusion rate was 93.1% (54/58) in the MicroPort NeuroTech group and 97.0% (64/66) in the Axium group, with a common odds ratio of 0.208 (95% confidence interval, 0.023-1.914; P = 0.184). Complications were comparable between the groups. CONCLUSIONS: Compared with the Aixum coil, the Numen coil is safe and effective in treating small intracranial aneurysms. TRIAL REGISTRATION: (13/12/2016, NCT02990156).

Ferroptosis in tumor immunity and therapy.

Ferroptosis is a type of regulated cell death (RCD), and it plays an important role in the occurrence of diseases, especially the development of tumors. Ferroptosis of tumor cells affects the antitumor immunity and the immune response to treatment to varying degrees. Ferroptosis also plays a key role in immune cells. This review outlines the mechanism of the immune-related effects of ferroptosis pathways in tumor progression and treatment, and it discusses potential methods for improving antitumor immunity and enhancing the efficacy of current cancer treatments by targeting ferroptosis.

Comprehensive analysis of the prognostic implications and functional exploration of PAK gene family in human cancer.

BACKGROUND: The p21-activated kinase (PAK) family (PAKs) plays a key role in the formation and development of human tumors. However, a systematic analysis of PAKs in human cancers is lacking and the potential role of PAKs in cancer immunity has not been explored. METHODS: We used datasets from in The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression database (GTEx). RESULTS: Based on TCGA datasets most PAKs show noteworthy differences in expression between tumors and corresponding normal tissues or across different tumor tissues. Patients with high expression of PAKs often show a worse prognosis. However, copy number variation, mutation, and DNA methylation of PAKs have limited impact on tumor development. Further analysis showed that the impact of PAKs on immunity varies with the type of tumor and the respective tumor microenvironment. PAK1 and PAK4 may be stronger predictors of immune characteristics, and are more suitable as drugs and molecular therapeutic targets. Furthermore, Cox regression analysis revealed that a PAK gene signature could be used as an independent prognostic factor for lower grade glioma (LGG) and glioblastoma (GBM). Gene set enrichment analysis (GSEA) analysis indicated that PAK genes may affect the occurrence and development of GBM through the PI3K signaling pathway. Further experiments verified that PAK1 and AKT1 have a significant interaction in GBM cells, and inhibiting the overactivation of PAK1 can significantly inhibit the proliferation of GBM cells. CONCLUSIONS: Our study provides a rationale for further research on the prognostic and therapeutic potential of PAKs in human tumors.

Intrinsic immune evasion patterns predict temozolomide sensitivity and immunotherapy response in lower-grade gliomas.

BACKGROUND: Although intrinsic immune-evasion is important in cancer proliferation, metastasis and response to treatment, it is unclear whether intrinsic immune-evasion patterns of gliomas can aid in predicting clinical prognosis and determining treatment. METHODS: A total of 182 immune-evasion genes intrinsic to cancer were subjected to consensus clustering to identify immune-evasion patterns in 1421 patients with lower-grade glioma (LGG). The levels of each cancer hallmark were determined by the Gene Set Variant Analysis (GSVA) method, and immune cell infiltrations were quantified using two algorithms, the single-sample Gene Set Enrichment Analysis (ssGSEA) and the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) methods. IEVscore was determined by a method that combined univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression and principal component analysis (PCA). RESULTS: Transcriptional and genomic analysis showed that most immune evasion genes (IEVGs) were upregulated in LGGs, with aberrant expression driven by alterations in copy number variants (CNV). Based on the mRNA expression profiles of cancer-intrinsic IEVGs could be divided into three LGG subgroups with distinct prognosis, clinicopathological features and immune infiltrations. A combined scoring scheme designed to assess the immune-evasion levels of LGGs divided these 1421 patients into two subgroups that differed in IEVscores. LGG patients with low-IEVscore had a better prognosis, would be more likely to benefit from immune check-point inhibitors and would be more susceptible to temozolomide (TMZ) chemotherapy. CONCLUSION: Intrinsic immune evasion in the tumor microenvironment (TME) has a crucial effect on glioma formation. Quantitatively assessing the IEV scores of individual LGG patients could enhance knowledge about the intra-glioma microenvironment and lead to the development of individualized therapeutic strategies for patients with LGG.

Circ_CLIP2 promotes glioma progression through targeting the miR-195-5p/HMGB3 axis.

BACKGROUND: Circular RNA (circRNA) has been demonstrated to play key roles in regulating glioma progression. Understanding the regulatory mechanism of circRNA in glioma is vital to reveal the pathogenesis of glioma and develop novel therapeutic strategies. Therefore, our study focuses on the role and underlying mechanism of Circ_CLIP2 in glioma. METHODS: The expression of Circ_CLIP2, miR-195-5p and HMGB3 in glioma cells and tissues were analyzed using qRT-PCR. Cell proliferation was determined with colony formation and MTT assays. Cell cycle and apoptosis were examined by flow cytometry. Western blot was conducted for analyzing HMGB3, PCNA, Bax, Bcl-2, cleaved-caspase 3, Wnt-1 and ß-catenin. Dual-luciferase reporter assay was measured to investigate the interaction among Circ_CLIP2, miR-195-5p and HMGB3. RESULTS: The expression of Circ_CLIP2 and HMGB3 were increased while miR-195-5p was down-regulated in glioma cells and patients. Silencing of Circ_CLIP2 inhibited cell proliferation, enhanced cell apoptosis and inhibited the Wnt/ß-catenin signaling pathway. Circ_CLIP2 suppressed miR-195-5p expression by directly sponging miR-195-5p. MiR-195-5p inhibited HMGB3 expression via directly targeting HMGB3. Knockdown of miR-195-5p facilitated cell proliferation, inhibited cell apoptosis and activated Wnt/ß-catenin signaling, which were reversed by silencing of HMGB3. CONCLUSION: Knockdown of Circ_CLIP2 suppresses glioma progression by targeting miR-195-5p/HMGB3 thus inhibiting Wnt/ß-catenin signaling. This study may provide potential therapeutic targets against glioma.

Protein disulphide isomerase can predict the clinical prognostic value and contribute to malignant progression in gliomas.

Increasing evidence from structural and functional studies has indicated that protein disulphide isomerase (PDI) has a critical role in the proliferation, survival and metastasis of several types of cancer. However, the molecular mechanisms through which PDI contributes to glioma remain unclear. Here, we aimed to investigate whether the differential expression of 17 PDI family members was closely related to the different clinicopathological features in gliomas from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas data sets. Additionally, four subgroups of gliomas (cluster 1/2/3/4) were identified based on consensus clustering of the PDI gene family. These findings not only demonstrated that a poorer prognosis, higher WHO grade, lower frequency of isocitrate dehydrogenase mutation and higher 1p/19q non-codeletion status were significantly correlated with cluster 4 compared with the other clusters, but also indicated that the malignant progression of glioma was closely correlated with the expression of PDI family members. Moreover, we also constructed an independent prognostic marker that can predict the clinicopathological features of gliomas. Overall, the results indicated that PDI family members may serve as possible diagnostic markers in gliomas.

Clinical characteristics of 276 hospitalized patients with coronavirus disease 2019 in Zengdu District, Hubei Province: a single-center descriptive study.

BACKGROUND: We aimed to report the epidemiological and clinical characteristics of hospitalized patients with coronavirus disease-19 (COVID-19) in Zengdu District, Hubei Province, China. METHODS: Clinical data on COVID-19 inpatients in Zengdu Hospital from January 27 to March 11, 2020 were collected; this is a community hospital in an area surrounding Wuhan and supported by volunteer doctors. All hospitalized patients with COVID-19 were included in this study. The epidemiological findings, clinical features, laboratory findings, radiologic manifestations, and clinical outcomes of these patients were analyzed. The patients were followed up for clinical outcomes until March 22, 2020. Severe COVID-19 cases include severe and critical cases diagnosed according to the seventh edition of China's COVID-19 diagnostic guidelines. Severe and critical COVID-19 cases were diagnosed according to the seventh edition of China's COVID-19 diagnostic guidelines. RESULTS: All hospitalized COVID-19 patients, 276 (median age: 51.0 years), were enrolled, including 262 non-severe and 14 severe patients. The proportion of patients aged over 60 years was higher in the severe group (78.6%) than in the non-severe group (18.7%, p < 0.01). Approximately a quarter of the patients (24.6%) had at least one comorbidity, such as hypertension, diabetes, or cancer, and the proportion of patients with comorbidities was higher in the severe group (85.7%) than in the non-severe group (21.4%, p < 0.01). Common symptoms included fever (82.2% [227/276]) and cough (78.0% [218/276]). 38.4% (106/276) of the patients had a fever at the time of admission. Most patients (94.9% [204/276]) were cured and discharged; 3.6% (10/276) deteriorated to a critical condition and were transferred to another hospital. The median COVID-19 treatment duration and hospital stay were 14.0 and 18.0 days, respectively. CONCLUSIONS: Most of the COVID-19 patients in Zengdu had mild disease. Older patients with underlying diseases were at a higher risk of progression to severe disease. The length of hospital-stay and antiviral treatment duration for COVID-19 were slightly longer than those in Wuhan. This work will contribute toward an understanding of COVID-19 characteristics in the areas around the core COVID-19 outbreak region and serve as a reference for decision-making for epidemic prevention and control in similar areas.

The Prognostic Role of Glutathione Peroxidase 1 and Immune Infiltrates in Glioma Investigated Using Public Datasets.

BACKGROUND Glutathione peroxidase 1 (GPX1) is an essential component of the intracellular antioxidant enzyme system, but little is known about the role of GPX1 in the progression of malignancy in gliomas. Using public datasets, this study investigated the prognostic role of GPX1 and immune infiltrates in glioma. MATERIAL AND METHODS We investigated GPX1 expression levels in different cancers using the ONCOMINE and Tumor Immune Estimation Resource (TIMER) datasets. We also explored the prognostic landscape of GPX1 in gliomas based on The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets. Some significant pathways were identified by function enrichment analysis. We then explored the association between GPX1 expression and levels of tumor-infiltrating immune cells based on TIMER and Gene Expression Profiling Interactive Analysis (GEPIA) datasets. RESULTS Expression of GPX1 in brain and central nervous system cancers is at a much high level than in normal tissues, and it is higher in glioblastoma (GBM) than in lower-grade glioma (LGG). We found GPX1 expression to be positively correlated with the malignant clinicopathologic characteristics of gliomas. Univariate analysis and multivariate analysis revealed that overexpression of GPX1 was correlated with a worse prognosis in patients, and a nomogram indicated that GPX1 expression can predict clinical prognosis of glioma. Function enrichment analysis showed that some important pathways are related to glioma malignancy. Expression of GPX1 was positively associated with infiltrating levels of 6 types of immune cells and most of their gene markers in GBM and LGG. CONCLUSIONS These results indicate that GPX1 is an independent prognostic factor and a novel biomarker for predicting the progression of malignancy in gliomas, which is associated with immune infiltration.

Di-2-ethylhexyl phthalate (DEHP) induces apoptosis of mouse HT22 hippocampal neuronal cells via oxidative stress.

Di-2-ethylhexyl phthalate (DEHP) has been widely used as a plasticizer in industry and can affect memory; however, the underlying mechanism remains unclear. In the present study, mouse HT22 cells, an immortalized hippocampal neuronal cell line, was utilized as an in vitro model. We showed that DEHP dramatically inhibited cell viability and increased lactate dehydrogenase (LDH) release from the cells in a dose-dependent manner, suggesting that DEHP could cause cytotoxicity of mouse HT22 cells. The protein levels of cleaved Caspase-8, cleaved Caspase-3, and Bax markedly increased in the DEHP-treated cells, whereas there was a significant decrease in the Bcl-2 protein level, implying that DEHP could induce apoptosis of mouse HT22 cells. DEHP exposure significantly increased the content of malondialdehyde, whereas it markedly decreased the level of glutathione and the activities of glutathione peroxidase and superoxide dismutase, suggesting that DEHP induced oxidative stress of the cells. Compared with the DEHP-treated group, the inhibition of cell viability and the release of LDH were rescued in the N-acetyl-l-cysteine plus DEHP group. Furthermore, inhibition of oxidative stress could rescue the induction of apoptosis by DEHP. Collectively, our results indicated that DEHP could induce apoptosis of mouse HT22 cells via oxidative stress.

Functional requirement of a wild-type allele for mutant IDH1 to suppress anchorage-independent growth through redox homeostasis.

Mutations of isocitrate dehydrogenase 1 (IDH1) gene are most common in glioma, arguably preceding all known genetic alterations during tumor development. IDH1 mutations nearly invariably target the enzymatic active site Arg132, giving rise to the predominant IDH1R132H. Cells harboring IDH1 R132H -heterozygous mutation produce 2-hydroxyglutarate (2-HG), which results in histone and DNA hypermethylation. Although exogenous IDH1 R132H transduction has been shown to promote anchorage-independent growth, the biological role of IDH1R132H in glioma remains debatable. In this study, we demonstrate that heterozygous IDH1 R132H suppresses but hemizygous IDH1 R132H promotes anchorage-independent growth. Whereas genetic deletion of the wild-type allele in IDH1 R132H -heterozygous cells resulted in a pronounced increase in neurosphere genesis, restoration of IDH1 expression in IDH1 R132H -hemizygous cells led to the contrary. Conversely, anchorage-independent growth was antagonistic to the mutant IDH1 function by inhibiting gene expression and 2-HG production. Furthermore, we identified that in contrast to IDH1 R132H -hemizygous neurosphere, IDH1 R132H -heterozygous cells maintained a low level of reducing power to suppress neurosphere genesis, which could be bypassed, however, by the addition of reducing agent. Taken together, these results underscore the functional importance of IDH1 mutation heterozygosity in glioma biology and indicate functional loss of mutant IDH1 as an escape mechanism underlying glioma progression and the pathway of redox homeostasis as potential therapeutic targets.

HP1α is highly expressed in glioma cells and facilitates cell proliferation and survival.

Epigenetic alteration plays critical roles in gliomagenesis by regulating gene expression through modifications of Histones and DNA. Trimethylation of H3K9, an essential repressed transcription mark, and one of its methyltransferase, SUV39H1, are implicated in glioma pathogenesis and progression. We find that the protein level of HP1α, a reader of H3K9me3 is elevated in cultured glioma cell lines and glioma tissues. H3K9me3 is also upregulated. Depletion of HP1α and SUV39H1 weakens glioma cell proliferation capacity and results in apoptosis of cells. Furthermore, we find that HP1α and H3K9me3 are enriched in the FAS and PUMA promoters, which suggests that upregulated HP1α and H3K9me3 contribute to cell survival by suppressing apoptotic activators. These data suggests that up-regulated HP1α and H3K9me3 in glioma cells are functionally associated with glioma pathogenesis and progression and may serve as novel biomarkers for diagnostic and therapeutic targeting of brain tumors.

A risk score based on admission characteristics to predict progressive hemorrhagic injury from traumatic brain injury in children.

Traumatic brain injury (TBI) is one of the leading causes of death and disability in children, and progressive hemorrhagic injury (PHI) post TBI is associated with poor outcomes. Therefore, the objective of this study was to develop and validate a prognostic model that uses the information available at admission to determine the likelihood of PHI occurrence after TBI in children. The identified demographic data, cause of injury, clinical predictors on admission, computed tomography scan characteristics, and routine laboratory parameters were collected and used to develop a PHI prognostic model with logistic regression analysis, and the prediction model was validated in 68 children. Eight independent prognostic factors were identified: lower Glasgow coma scale score (3 ~ 8) (6 points), intra-axial bleeding/brain contusion (4 points), midline shift ≥5 mm (9 points), platelets <100 × 109/L (11 points), prothrombin time >14 s (6 points), international normalized ratio >1.25 (7 points), D-dimer ≥5 mg/L (14 points), and glucose ≧10 mmol/L (11 points). We calculated risk scores for each child and defined three risk groups: low risk (0-16 points), intermediate risk (17-36 points), and high risk (37-68 points). In the development cohort, the PHI rates after TBI for the low-, intermediate-, and high-risk groups were 10.1, 47.9, and 84.2%, respectively. In the validation cohort, the corresponding PHI rates were 10.9, 47.5, and 85.4%, respectively. The C-statistic for the point system was 0.873 (p = 0.586 by the Hosmer-Lemeshow test) in the development cohort and 0.877 (p = 0.524 by the Hosmer-Lemeshow test) in the validation cohort. CONCLUSION: Using admission predictors, we developed a relatively simple risk score that accurately predicted the risk of PHI after TBI in children. What is Known: • TBI is one of the leading causes of death and disability in children, and PHI post TBI is associated with poor outcomes. •Prediction of patients at low risk of PHI could help reduce treatment costs, whereas identification of patients at high risk of PHI could direct early medical intervention to improve outcomes. What is New: • This study firstly developed a risk score system by assessing the admission information that could provide an earlier prediction of the occurrence of PHI after acute TBI in children.

Annexin A5 promotes invasion and chemoresistance to temozolomide in glioblastoma multiforme cells.

Glioblastoma multiforme (GBM) is the prevalent and most fatal brain tumor in adults. Invasion and a high rate of recurrence largely contribute to the poor prognosis of GBM. The current standard therapy for GBM includes surgery with maximum feasible resection, radiotherapy, and treatment with chemotherapeutic agent temozolomide. Annexin A5 reportedly promotes progression and chemoresistance in a variety of cancers. In the present study, we explored the effects of annexin A5 on GBM cell invasion and chemoresistance to temozolomide. Stable overexpression and knockdown of annexin A5 were performed in both U-87 MG and U-118 MG human GBM cell lines. Overexpression of annexin A5 in both cell lines significantly increased cell invasion, matrix metalloproteinase-2 (MMP-2) expression/activity, Akt phosphorylation at serine 473, and the half maximal inhibitory concentration (IC50) values of temozolomide and markedly decreased temozolomide-induced apoptosis, all of which were abolished by selective PI3K inhibitor BKM120. On the other hand, knockdown of annexin A5 markedly decreased cell invasion, MMP-2 expression/activity, Akt phosphorylation at serine 473, and the IC50 values of temozolomide and significantly increased temozolomide-induced apoptosis. In conclusion, our study provides the first evidence that annexin A5 promotes GBM cell invasion, MMP-2 expression/activity, and chemoresistance to temozolomide through a PI3K-dependent mechanism. It adds new insights not only into the biological function of annexin A5 but also into the molecular mechanisms underlying GBM progression and chemoresistance.

PSMB2 plays an oncogenic role in glioma and correlates to the immune microenvironment.

There has been an upward trend in the incidence of glioma, with high recurrence and high mortality. The beta subunits of the 20S proteasome are encoded by the proteasome beta (PSMB) genes and may affect the proteasome's function in glioma, assembly and inhibitor binding. This study attempted to reveal the function of the proliferation and invasion of glioma cells, which is affected by proteasome 20S subunit beta 2 (PSMB2). We subjected the data downloaded from the TCGA database to ROC, survival, and enrichment analyses. After establishing the stable PSMB2 knockdown glioma cell line. We detect the changes in the proliferation, invasion and migration of glioma cells by plate colony formation assay, transwell assay, wound healing assay and flow cytometry and PSMB2 expression was verified by quantitative PCR and Western blotting to identify the mRNA and protein levels. PSMB2 expression was higher in glioma tissues, and its expression positively correlated with poor prognosis and high tumor grade and after PSMB2 knockdown, the proliferation, invasion and migration of glioma cells were weakened.

Aberrant RBMX expression is relevant for cancer prognosis and immunotherapy response.

Cancer accounts for the highest rates of morbidity and mortality worldwide. RNA binding motif protein X-linked (RBMX) is a nuclear RNA-binding protein, associated with certain types of cancer by participating in the integration of sister chromatids and a combination of ribonucleoprotein complexes. However, the specific role of RBMX in cancer immunity remains unknown. This study presents the aberrant expression levels, single-cell distributions, effective prognostic roles, immune cell infiltration associations, and immunotherapy responses of RBMX as a biomarker in various types of cancer. Moreover, it validates the aberrant expression of RBMX in clinical cancer samples. Furthermore, we also evaluated the relationships between RBMX expression and myeloid-derived suppressor cells in clinical samples by immunofluorescent staining. The results showed that knockdown of RBMX can impair the proliferation, migration, and invasion of liver cancer cells. Finally, we indicated that RBMX may play an immunoregulatory role in cancer progression, affecting the therapeutic effects of immune checkpoint inhibitors in patients with cancer.