Autocrine S100B in astrocytes promotes VEGF-dependent inflammation and oxidative stress and causes impaired neuroprotection.

Minimal hepatic encephalopathy (MHE) is strongly associated with neuroinflammation. Nevertheless, the underlying mechanism of the induction of inflammatory response in MHE astrocytes remains not fully understood. In the present study, we investigated the effect and mechanism of S100B, a predominant isoform expressed and released from mature astrocytes, on MHE-like neuropathology in the MHE rat model. We discovered that S100B expressions and autocrine were significantly increased in MHE rat brains and MHE rat brain-derived astrocytes. Furthermore, S100B stimulates VEGF expression via the interaction between TLR2 and RAGE in an autocrine manner. S100B-facilitated VEGF autocrine expression further led to a VEGFR2 and COX-2 interaction, which in turn induced the activation of NFƙB, eventually resulting in inflammation and oxidative stress in MHE astrocytes. MHE astrocytes supported impairment of neuronal survival and growth in a co-culture system. To sum up, a comprehensive understanding of the role of S100B-overexpressed MHE astrocyte in MHE pathogenesis may provide insights into the etiology of MHE.

ACT001 inhibits pituitary tumor growth by inducing autophagic cell death via MEK4/MAPK pathway.

ACT001, derived from traditional herbal medicine, is a novel compound with effective anticancer activity in clinical trials. However, little is known regarding its role in pituitary adenomas. Here, we demonstrated that ACT001 suppressed cell proliferation and induced cell death of pituitary tumor cells in vitro and in vivo. ACT001 was also effective in suppressing the growth of different subtypes of human pituitary adenomas. The cytotoxic mechanism ACT001 employed was mainly related to autophagic cell death (ACD), indicated by autophagosome formation and LC3-II accumulation. In addition, ACT001-mediated inhibitory effect decreased when either ATG7 was downregulated or cells were cotreated with autophagy inhibitor 3-methyladenine (3-MA). RNA-seq analysis showed that mitogen-activated protein kinase (MAPK) pathway was a putative target of ACT001. Specifically, ACT001 treatment promoted the phosphorylation of JNK and P38 by binding to mitogen-activated protein kinase kinase 4 (MEK4). Our study indicated that ACT001-induced ACD of pituitary tumor cells via activating JNK and P38 phosphorylation by binding with MEK4, and it might be a novel and effective anticancer drug for pituitary adenomas.

Lipidomic analysis and diagnosis of glioblastoma multiforme with rapid evaporative ionization mass spectrometry.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in the central nervous system. GBM patients have a very low 5-year survival rate and most of them died within 1 year. Conventional histopathological examination for GBM diagnosis is complicated and time-consuming, which always blocks the development of more precise and effective treatments in resection operation. Rapid evaporative ionization mass spectrometry (REIMS) is a MS technique in clinical medicine research, which combines the common diathermy device with MS to acquire the lipid profiles of tissue specimens for lipidomic analysis and real-time tumor diagnosis. In this study, the REIMS method employing bipolar forceps was optimized and validated for high-throughput lipidomics and diagnosis of GBM for the first time. Total 42 lipid metabolites were tentatively identified and 12 out of 13 lipid biomarkers showed higher intensities in GBM, which were consistent with previous studies. After this, a statistic model was built with the lipidomic data for the diagnosis of GBM tumor in real-time. The diagnostic accuracy (94.74%), sensitivity (95.38%), and specificity (93.33%) were evaluated with histopathology validated brain tissue specimens that were not used in the training set. The proposed REIMS method for the lipidomic-analysis and diagnosis of GBM tumor provides a new direction for MS-based lipidomics and precision medicine and might be used to guide surgeons to precisely resect the GBM tissue and keep the normal brain tissue in operation.

Regenerative Potential of Menstrual Blood-Derived Stem Cells and Platelet-Derived Growth Factor in Endometrial Injury.

BACKGROUND Endometrial regeneration is essential for normal endometrial function; however, it is unclear whether and how menstrual blood-derived stem cells (MenSCs) and platelet-derived growth factor (PGDF) are associated with this phenomenon. The present study explored this topic. MATERIAL AND METHODS EM-E6/E7/hTERT cells were divided into 5 groups: control group, NC group, PDGF group, MenSCs group, and PDGF+MenSCs group. The effects of MenSCs and PDGF on cell proliferation, invasion, and microvascular formation of endometrial epithelium were investigated by CCK-8, Transwell, and tube formation assays, respectively. Mouse endometrial injury models were established and mice were randomly divided into control, model, PDGF, MenSCs, and PDGF+MenSCs groups. Pathological change was examined with hematoxylin and eosin (H&E) staining. Microvessel formation of endometrial epithelium was estimated by detecting the expression of CD34 protein with immunohistochemical (IHC) staining. Western blot analysis was used to detect the activation of Akt and Bad proteins in endometrial tissue. RESULTS MenSCs, PDGF, and the combination treatments significantly promoted the proliferation, migration, and tube formation of endometrial epithelium compared to the control and NC group. The combination of MenSCs and PDGF remarkably promoted re-epithelialization and endometrial repair. IHC staining analysis showed significant increases in CD34 expression of the endometrial tissue following treatment with PDGF and MenSCs. The combination treatments also markedly enhanced the phosphorylation of Akt and Bad in endometrial tissue. CONCLUSIONS These results suggest that MenSCs and PDGF may be candidate substances for endometrial injury repair.

Calpain suppresses cell growth and invasion of glioblastoma multiforme by producing the cleavage of filamin A.

BACKGROUND: Filamin A is the most widely expressed isoform of filamin in mammalian tissues. It can be hydrolyzed by Calpain, producing a 90-kDa carboxyl-terminal fragment (ABP90). Calpeptin is a chemical inhibitor of Calpain, which can inhibit this effect. It has been shown that ABP90 acts as a transcription factor which is involved in mediating cell signaling. However, the significance of ABP90 and its clinical signature with underlying mechanisms have not been well studied in glioblastoma multiforme (GBM). METHODS: ABP90 protein was measured in 36 glioma patients by Western blot. Human GBM cell lines U87 and A172 were used to clarify the precise role of ABP90. CCK-8 assay was used to analyze the cell viability. Transwell invasion assay and wound healing assay were used to analyze the migration and invasion. Expression of matrix metalloproteinase 2/tissue inhibitors of metalloproteinase 2 (MMP2/TIMP2) protein was analyzed by Western blot. RESULTS: ABP90 protein expression was lower in GBM tissues. The patients with low ABP90 protein expression had a shorter OS time (p = 0.046). After being treated with Calpain, the expression of ABP90 was upregulated, which led to a decline of cell viability, enhanced the efficacy of temozolomide and restrained the cell invasion. Calpeptin could inhibit the effect. The mechanism might be involved in the balance of MMP2/TIMP2. CONCLUSIONS: Our present data suggest that ABP90 expression is a significant prognostic factor and may play an important role in cell viability, chemotherapeutic sensitivity and invasion of GBM.

Long non-coding RNA LOC730100 enhances proliferation and invasion of glioma cells through competitively sponging miR-760 from FOXA1 mRNA.

Glioma is the most malignant cancer in central nervous system. And researchers have indicated that long noncoding RNAs (lncRNAs) are closely related with glioma progression. Nevertheless, LOC730100 function in glioma is ill studied. In the current research, we showed that LOC730100 expression was increased in glioma tissues and cell lines. Furthermore, LOC730100 upregulation is linked to a poor prognosis in glioma patients. Loss-of-function assays showed that LOC730100 knockdown inhibited proliferation, migration and invasion of glioma cells, but increasing apoptosis. Notably, we found that LOC730100 was mainly localized in the cytoplasm of glioma cells. We demonstrated that LOC730100 was a competing endogenous RNA (ceRNA) for miR-760 and promoted the expression of FOXA1. We proved that miR-760 suppresses glioma progression and FOXA1 overexpression reversed it. In conclusion, our findings revealed that LOC730100 promoted glioma progression through regulating miR-760/FOXA1 axis.

RBM17 controls apoptosis and proliferation to promote Glioma progression.

The splicing factor SPF45 (RBM17) is a well-known component of the spliceosome that is involved in alternative splicing. RBM17 is frequently overexpressed in many tumors and plays a crucial role in cancer progression and drug resistance. However, the role of RBM17 in the development of glioma has not been thoroughly elucidated to date. In the present study, we found that RBM17 was overexpressed in glioma and that a high level of expression of RBM17 was closely associated with a poor prognosis in glioma patients. We investigated the effect of RBM17 on apoptosis, cell growth and cell cycle indexes and the activation of apoptosis signaling by shRNA in human U87 and U251 glioma cells. The downregulated expression of RBM17 mRNA was accompanied by the induction of cell cycle arrest, and apoptosis, reduced cell proliferation in the two cell lines, and reduced cell survival, as measured by the increased activation of caspase-3, caspase-9, and PARP (poly ADP-ribose polymerase). Furthermore, in subcutaneous U87 cell xenograft tumors in nude mice, intradermal administration of an shRNA targeting RBM17 significantly downregulated RBM17 expression in vivo and was accompanied by the suppressed growth of glioma. To the best of our knowledge, our results are the first to confirm that RBM17 functions in promoting cell proliferation, affecting the cell cycle, and inducing apoptosis in human glioma cells both in vitro and in vivo. These results indicate that RBM17 may be a therapeutic target in the clinical management of glioma.

Src Promotes Metastasis of Human Non-Small Cell Lung Cancer Cells through Fn14-Mediated NF-κB Signaling.

BACKGROUND Src and Fn14 are implicated in the aggressiveness of non-small cell lung cancer (NSCLC) cells, yet the molecular mechanism is not fully understood. MATERIAL AND METHODS The proliferation, migration, and invasion of HCC827 cells with Src knockdown were examined in vitro. The expression of Fn14 and the activation of NF-κB signaling pathway in Src-silenced HCC827 cells were detected by western blot. The role of Fn14 in Src-regulated cell migration/invasion and activation of NF-κB signaling was investigated by overexpressing Fn14 in Src knockdown NSCLC cells. Furthermore, the pro-metastatic role of Src was validated in a NSCLC metastasis mouse model. RESULTS Knockdown of Src inhibited the proliferation, migration, and invasion of HCC827 cells, which was associated with reduced levels of Fn14, p-IκBα, p-IKKß, and nuclear NF-κB p65. Overexpression of Fn14 restored the potential of migration and invasion as well as the activation of NF-κB signaling in Src-silenced NSCLC cells. In addition, silencing of Src suppressed lung metastasis of HCC827 cells in mice, and inhibited the expression of Fn14 and nuclear translocation of NF-κB p65 in vivo. CONCLUSIONS The data demonstrated that the Src/Fn14/NF-κB axis plays a critical role in NSCLC metastasis.

Global expression profile of tumor stem-like cells isolated from MMQ rat prolactinoma cell.

BACKGROUND: Cancer stem cells (CSCs), which have been isolated from various malignancies, were closely correlated with the occurrence, progression, metastasis and recurrence of the malignant cancer. Little is known about the tumor stem-like cells (TSLCs) isolated from benign tumors. Here we want to explore the global expression profile of RNA of tumor stem-like cells isolated from MMQ rat prolactinoma cells. METHODS: In this study, total RNA was extracted from MMQ cells and MMQ tumor stem-like cells. RNA expression profiles were determined by Agilent Rat 8 × 60 K Microarray. Then we used the qRT-PCR to test the result of Microarray, and found VEGFA had a distinct pattern of expression in MMQ tumor stem-like cells. Then WB and ELISA were used to confirm the VEGFA protein level of tumor sphere cultured from both MMQ cell and human prolactinoma cell. Finally, CCK-8 was used to evaluate the reaction of MMQ tumor stem-like cells to small interfering RNAs intervention and bevacizumab treatment. RESULT: The results of Microarray showed that 566 known RNA were over-expressed and 532 known RNA were low-expressed in the MMQ tumor stem-like cells. These genes were mainly involved in 15 different signaling pathways. In pathway in cancer and cell cycle, Bcl2, VEGFA, PTEN, Jun, Fos, APC2 were up-regulated and Ccna2, Cdc25a, Mcm3, Mcm6, Ccnb2, Mcm5, Cdk1, Gadd45a, Myc were down-regulated in the MMQ tumor stem-like cells. The expression of VEGFA were high in tumor spheres cultured from both MMQ cell and human prolactinomas. Down-regulation of VEGFA by small interfering RNAs partially decreased cell viability of MMQ tumor stem-like cells in vitro. Bevacizumab partially suppressed the proliferation of MMQ tumor stem-like cells. CONCLUSIONS: Our findings characterize the pattern of RNA expression of tumor stem-like cells isolated from MMQ cells. VEGFA may act as a potential therapeutic target for tumor stem-like cells of prolactinomas.

Expression of Stem Cell Markers and Dopamine D2 Receptors in Human and Rat Prolactinomas.

BACKGROUND Dopamine agonists (DAs) are the first-line treatment for prolactinomas. DAs primarily target the dopamine D2 receptor (D2R). Tumor stem-like cells (TSLCs) are associated with the tolerance to radiotherapy and chemotherapy. TSLCs have also been identified in pituitary adenomas. We aimed to characterize the expression pattern of stem cell markers and D2R in human and rat prolactinomas. MATERIAL AND METHODS Human prolactinoma specimens (n=14) were obtained from patients with surgical resection. The xenograft model of rat prolactinomas was generated by endermically injecting MMQ cells, HE and PRL were confirmed by immunohistochemical staining of tumor sections, and the expression of serum PRL was measured by ELISA. The expression of stem cell markers (CD133, Nestin, Oct4, and Sox2) and D2R in prolactinomas was detected by immunofluorescence. The proportion of CD133-expressing cells after DA treatment was evaluated by flow cytometry in vitro. RESULTS We found that a small subpopulation of cells expressing stem cell markers existed both in human and rat prolactinomas. Furthermore, the CD133-expressing cells showed negative D2R expression. Conversely, the D2R-expressing cells showed negative CD133 expression. The proportion of CD133-expressing cells in surviving tumor cells was significantly increased after DA treatment. CONCLUSIONS Our results confirmed the existence of cells expressing stem cell markers in human and rat prolactinomas. Additionally, the CD133-expressing cells might resist DA therapy due to the lack of D2R expression.

Antiproliferative and apoptosis-inducing activity of schisandrin B against human glioma cells.

BACKGROUND: Malignant glioma is the most devastating and aggressive tumour in the brain and is characterised by high morbidity, high mortality and extremely poor prognosis. The main purpose of the present study was to investigate the effects of schisandrin B (Sch B) on glioma cells both in vitro and in vivo and to explore the possible anticancer mechanism underlying Sch B-induced apoptosis and cell cycle arrest. METHODS: The anti-proliferative ability of Sch B on glioma cells were assessed by MTT and clony formation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by Hoechst 33342 staining and annexin V/PI double-staining assays. The mitochondrial membrane potential was detected by Rhodamine 123 staining. The in vivo efficacy of Sch B was measured using a U87 xenograft model in nude mice. The expressions of the apoptosis-related and cell cycle-related proteins were analysed by western blot. Student's t-test was used to compare differences between treated groups and their controls. RESULTS: We found that Sch B inhibited growth in a dose- and time-dependent manner as assessed by MTT assay. In U87 and U251 cells, the number of clones was strongly suppressed by Sch B. Flow cytometric analysis revealed that Sch B induced cell cycle arrest in glioma cells at the G0/G1 phase. In addition, Sch B induced glioma cell apoptosis and reduced mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Mechanically, western blot analysis indicated that Sch B induced apoptosis by caspase-3, caspase-9, PARP, and Bcl-2 activation. Moreover, Sch B significantly inhibited tumour growth in vivo following the subcutaneous inoculation of U87 cells in athymic nude mice. COCLUSIONS: In summary, Sch B can reduce cell proliferation and induce apoptosis in glioma cells and has potential as a novel anti-tumour therapy to treat gliomas.

Deep learning for rapid virtual H&E staining of label-free glioma tissue from hyperspectral images.

Hematoxylin and eosin (H&E) staining is a crucial technique for diagnosing glioma, allowing direct observation of tissue structures. However, the H&E staining workflow necessitates intricate processing, specialized laboratory infrastructures, and specialist pathologists, rendering it expensive, labor-intensive, and time-consuming. In view of these considerations, we combine the deep learning method and hyperspectral imaging technique, aiming at accurately and rapidly converting the hyperspectral images into virtual H&E staining images. The method overcomes the limitations of H&E staining by capturing tissue information at different wavelengths, providing comprehensive and detailed tissue composition information as the realistic H&E staining. In comparison with various generator structures, the Unet exhibits substantial overall advantages, as evidenced by a mean structure similarity index measure (SSIM) of 0.7731 and a peak signal-to-noise ratio (PSNR) of 23.3120, as well as the shortest training and inference time. A comprehensive software system for virtual H&E staining, which integrates CCD control, microscope control, and virtual H&E staining technology, is developed to facilitate fast intraoperative imaging, promote disease diagnosis, and accelerate the development of medical automation. The platform reconstructs large-scale virtual H&E staining images of gliomas at a high speed of 3.81 mm2/s. This innovative approach will pave the way for a novel, expedited route in histological staining.

Dynamic stratified porosity computation from canopy interaction simulation between airflow and leaves.

The main goal of wind-driven spraying is to use assisted airflow to disrupt the structure of branches and leaves and broaden the air delivery channel, so as to achieve uniform droplet deposition in the middle and lower parts of the canopy. Due to the complex branch and leaf structure inside the canopy, there is currently no effective method to express the dynamic changes of canopy porosity and the law of airflow attenuation under assisted airflow. In this study, based on the two-way fluid-structure interaction numerical simulation method, the relating between the assisted airflow and the structural parameters of the cotton canopy is analyzed, and a new method for predicting and simulating the dynamic porosity of the canopy is proposed. Firstly, a two-way fluid-structure interaction model based on Lattice Boltzmann (LB) solver and Finite Element (FE) solver is developed to simulate the deformation motion of cotton leaves and the spatial distribution of airflow field, and the correctness of the numerical simulation is verified based on indoor measurement data. Secondly, the post-processing method of Computational Fluid Dynamics (CFD) is used to obtain images of leaves at different canopy positions under assisted airflow, and the porosity changes are calculated and analyzed by image processing. The research results show that under different initial wind speeds (5 m·s-1, 10 m·s-1, 15 m·s-1), the maximum normalized mean absolute error (NMAE) between the simulated values and the measured values is 13.99%, 20.72% and 16.08%, respectively. The coefficient of determination (R2) for linear fitting between simulated values and measured values is 0.9221. These validation results indicate the effectiveness of the numerical simulation method. The validated CFD model is applied to predict leaf deformation and porosity changes within the canopy under various wind loads and times. The application results have well revealed the interaction between crop leaves and airflow, and will be beneficial to make a better understanding of the effect of assisted airflow on droplet deposition.

Expression of dopamine 2 receptor subtype mRNA in clinically nonfunctioning pituitary adenomas.

Dopamine receptor agonists (DAs) can reduce hormone release and tumor mass in the majority of prolactinomas, whereas such effects are controversial in clinically nonfunctioning pituitary adenomas (NFPAs). Whether expression of dopamine 2 receptor (D2R) is different in subgroups of NFPAs has not been fully elucidated. We assessed and compared D2R subtype (long: D2L and short: D2S) mRNA levels in subgroups of NFPAs by real-time reverse transcriptase polymerase chain reaction (RT-PCR). For both D2L and D2S mRNA, there were no significant differences among them. Only 21.6% of NFPAs showed relatively high D2R mRNA levels; furthermore, histopathological subtypes of those cases with relatively high D2R expression were gonadotropinomas and null-cell adenomas. These data suggest that DAs are effective only for a small proportion of NFPAs, and relatively high D2R expression may more possibly happen to a subset of gonadotropinomas and null-cell adenomas.

[Differential expression analysis of prolactinoma-related microRNAs].

OBJECTIVE: To explore the relationship between the prolactinoma-related microRNAs (miRNA) and the development, growth and hormone secretion of prolactinoma. METHODS: The technique of Solexa sequencing was employed to analyze the differential expressions of prolactinoma and normal anterior pituitary gland samples. And the stem-loop real-time polymerase chain reaction (PCR) was utilized for confirmation. RESULTS: According to the differentially expressed profiles of miRNAs, 4 miRNAs were down-regulated (miR-130a, miR-199b-3p, miR-200b, miR-125b, P < 0.05) and 6 miRNAs up-regulated (miR-342-3p, miR-432, miR-23b, miR-493, miR-493(*), miR-664(*), P < 0.05). The expression levels of miR-493(*) and miR-432 had a significant positive correlation with the serum level of prolactin (r = 0.47, P < 0.05; r = 0.528, P < 0.01) while miR-342-3p a significantly positive correlation with the invasiveness (r = 0.402, P < 0.05). CONCLUSION: miRNAs are differentially expressed between normal anterior pituitary gland and prolactinomas, between invasive and localized prolactinomas and among different hormone secretion levels. It suggests that miRNAs may be involved in the physiological process of development, growth and hormone secretion of prolactinoma.

Mechanism of action of paclitaxel for treating glioblastoma based on single-cell RNA sequencing data and network pharmacology.

Paclitaxel is an herbal active ingredient used in clinical practice that shows anti-tumor effects. However, its biological activity, mechanism, and cancer cell-killing effects remain unknown. Information on the chemical gene interactions of paclitaxel was obtained from the Comparative Toxicogenomics Database, SwishTargetPrediction, Binding DB, and TargetNet databases. Gene expression data were obtained from the GSE4290 dataset. Differential gene analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology analyses were performed. Gene set enrichment analysis was performed to evaluate disease pathway activation; weighted gene co-expression network analysis with diff analysis was used to identify disease-associated genes, analyze differential genes, and identify drug targets via protein-protein interactions. The Molecular Complex Detection (MCODE) analysis of critical subgroup networks was conducted to identify essential genes affected by paclitaxel, assess crucial cluster gene expression differences in glioma versus standard samples, and perform receiver operator characteristic mapping. To evaluate the pharmacological targets and signaling pathways of paclitaxel in glioblastoma, the single-cell GSE148196 dataset was acquired from the Gene Expression Omnibus database and preprocessed using Seurat software. Based on the single-cell RNA-sequencing dataset, 24 cell clusters were identified, along with marker genes for the two different cell types in each cluster. Correlation analysis revealed that the mechanism of paclitaxel treatment involves effects on neurons. Paclitaxel may affect glioblastoma by improving glucose metabolism and processes involved in modulating immune function in the body.

Construction and validation of a glioblastoma prognostic model based on immune-related genes.

Background: Glioblastoma multiforme (GBM) is a common malignant brain tumor with high mortality. It is urgently necessary to develop a new treatment because traditional approaches have plateaued. Purpose: Here, we identified an immune-related gene (IRG)-based prognostic signature to comprehensively define the prognosis of GBM. Methods: Glioblastoma samples were selected from the Chinese Glioma Genome Atlas (CGGA). We retrieved IRGs from the ImmPort data resource. Univariate Cox regression and LASSO Cox regression analyses were used to develop our predictive model. In addition, we constructed a predictive nomogram integrating the independent predictive factors to determine the one-, two-, and 3-year overall survival (OS) probabilities of individuals with GBM. Additionally, the molecular and immune characteristics and benefits of ICI therapy were analyzed in subgroups defined based on our prognostic model. Finally, the proteins encoded by the selected genes were identified with liquid chromatography-tandem mass spectrometry and western blotting (WB). Results: Six IRGs were used to construct the predictive model. The GBM patients were categorized into a high-risk group and a low-risk group. High-risk group patients had worse survival than low-risk group patients, and stronger positive associations with multiple tumor-related pathways, such as angiogenesis and hypoxia pathways, were found in the high-risk group. The high-risk group also had a low IDH1 mutation rate, high PTEN mutation rate, low 1p19q co-deletion rate and low MGMT promoter methylation rate. In addition, patients in the high-risk group showed increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy than those in the low-risk group. Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by protein mass spectrometry and WB. Conclusion: Herein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research.

A Multielement Prognostic Nomogram Based on a Peripheral Blood Test, Conventional MRI and Clinical Factors for Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most malignant types of tumors in the central nervous system, and the 5-year survival remains low. Several studies have shown that preoperative peripheral blood tests and preoperative conventional Magnetic Resonance Imaging (MRI) examinations affect the prognosis of GBM patients. Therefore, it is necessary to construct a risk score based on a preoperative peripheral blood test and conventional MRI and develop a multielement prognostic nomogram for GBM. METHODS: This study retrospectively analyzed 131 GBM patients. Determination of the association between peripheral blood test variables and conventional MRI variables and prognosis was performed by univariate Cox regression. The nomogram model, which was internally validated using a cohort of 56 GBM patients, was constructed by multivariate Cox regression. RNA sequencing data from Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA datasets were used to determine peripheral blood test-related genes based on GBM prognosis. RESULTS: The constructed risk score included the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), albumin/fibrinogen (AFR), platelet/lymphocyte ratio (PLR), and center point-to-ventricle distance (CPVD). A final nomogram was developed using factors associated with prognosis, including age, sex, the extent of tumor resection, IDH mutation status, radiotherapy status, chemotherapy status, and risk. The Area Under Curve (AUC) values of the receiver operating characteristic curve (ROC) curve were 0.876 (12-month ROC), 0.834 (24-month ROC) and 0.803 (36-month ROC) in the training set and 0.906 (12-month ROC), 0.800 (18-month ROC) and 0.776 (24-month ROC) in the validation set. In addition, vascular endothelial growth factor A (VEGFA) was closely associated with NLR and LMR and identified as the most central negative gene related to the immune microenvironment and influencing immune activities. CONCLUSION: The risk score was established as an independent predictor of GBM prognosis, and the nomogram model exhibit appropriate predictive power. In addition, VEGFA is the key peripheral blood test-related gene that is significantly associated with poor prognosis.

Ubiquitination of p21 by E3 Ligase TRIM21 Promotes the Proliferation of Human Neuroblastoma Cells.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, which shows great clinical and biomolecule heterogeneity. Currently, surgery is still the main method of neuroblastoma treatment and specific therapeutic drugs are lacking, so useful targets are urgently needed. TRIM21 is a RING-type E3 ligase that its overexpression promotes the progression of human glioma, while whose effects on neuroblastoma have not been illustrated. Firstly, the shRNAs targeting TRIM21 were designed and found that the ablation of TRIM21 inhibits the proliferation of human neuroblastoma cells. Then the molecular mechanism study indicated that TRIM21 interacts with, and mediates p21 degradation by ubiquitination modification. Further study demonstrates that TRIM21 regulates the proliferation of neuroblastoma cells in a p21-dependent manner. These results suggest that TRIM21 might be a potential therapeutic target for neuroblastoma.

Brusatol Inhibits Proliferation and Invasion of Glioblastoma by Down-Regulating the Expression of ECM1.

Brusatol (Bru), a Chinese herbal extract, has a variety of anti-tumor effects. However, little is known regarding its role and underlying mechanism in glioblastoma cells. Here, we found that Bru could inhibit the proliferation of glioblastoma cells in vivo and in vitro. Besides, it also had an inhibitory effect on human primary glioblastoma cells. RNA-seq analysis indicated that Bru possibly achieved these effects through inhibiting the expression of extracellular matrix protein 1 (ECM1). Down-regulating the expression of ECM1 via transfecting siRNA could weaken the proliferation and invasion of glioblastoma cells and promote the inhibitory effect of Bru treatment. Lentivirus-mediated overexpression of ECM1 could effectively reverse this weakening effect. Our findings indicated that Bru could inhibit the proliferation and invasion of glioblastoma cells by suppressing the expression of ECM1, and Bru might be a novel effective anticancer drug for glioblastoma cells.