黑色素瘤是一种能产生黑色素的高度恶性肿瘤,占皮肤肿瘤死亡病例的绝大部分,多发生于皮肤或接近皮肤的粘膜,也见于软脑膜和脉络膜。该病以白种人的发病率最高,中国虽然不属于高发地区,但是在进入21世纪后呈现逐年上升的趋势。手术切除是其首选治疗方法,尽管术后辅以放疗等辅助治疗,但其远期效果欠佳。采用免疫疗法等新的治

黄疸是由于血清中胆红素升高导致皮肤巩膜发黄的症状和体征。在正常情况下,胆红素进入和离开血液循环保持动态平衡,因其代谢异常导致血清中胆红素升高而出现黄疸。引起黄疸的原因很多,按病因可分为溶血性黄疸、胆汁淤积性黄疸、肝细胞性黄疸、先天性非溶血性黄疸等。而心功能不全患者由于严重心脏疾病导致有效循环血量减少、肝

Background. This study aims to develop novel signatures for glioblastoma multiforme (GBM). Methods. GBM expression profiles from The Cancer Genome Atlas (TCGA) were downloaded and DEGs between tumor and normal samples were identified by differential expression analysis (DEA). A risk signature was developed by applying weighted gene coexpression network analysis (WGCNA) and Cox regression analysis. Patients were divided into high and low risk group, followed by evaluating the performance of the signature via Kaplan-Meier curve analysis. In addition, the prognostic significance of the signature was further validated using an independent validation dataset from Chinese Glioma Genome Atlas (CGGA). DEGs between high and low risk group were subjected to functional annotation. Results. A total of 748 DEGs were identified between primary tumor and normal samples. Following WGCNA and Cox regression analysis, 6 DEGs were identified and used to construct a risk signature. The signature showed high performance in both training and validation dataset. Subsequently, 397 DEGs were identified between high and low risk group. These DEGs were mainly enriched in terms related to calcium signaling, cAMP-mediated signaling, and synaptic transmission. Conclusions. The risk signature may contribute to GBM diagnosis in future clinical practice.

This study aimed to explore more gene markers associated with glioma or its prognosis. The glioma-related RNAseq data from the Gene Expression Omnibus database and The Cancer Genome Atlas dataset in UCSC Xena database were downloaded. There was a total of 971 tumor samples and 102 normal samples in the 2 datasets. The differentially expressed genes (DEGs) data between tumor and normal samples were analyzed, on which were then performed function and pathway enrichment analyses. Pearson correlation coefficient between DEGs was calculated to construct the coexpression network. Finally, prognostic genes were screened. A total of 634 upregulated and 769 downregulated DEGs were identified between tumor and control groups. These DEGs were significantly involved in 15 upregulated pathways, such as p53 signaling pathway, and 16 downregulated pathways, such as neuroactive ligand-receptor interaction, and cell adhesion molecules. In the coexpression network, pseudouridine synthase 7 (PUS7), EFR3 homolog B (EFR3B), and neuronal cell adhesion molecule (NRCAM) had the top three highest degrees. Additionally, 17 prognostic genes were selected, such as thrombospondin-1 (THBS1), caspase-8 (CASP8), glutamate ionotropic receptor AMPA type subunit 2 (GRIA2), GRIA4, and ADCYAP receptor type I (ADCYAP1R1). Pathways of p53 signaling pathway and neuroactive ligand-receptor interaction may play important roles in glioma progression. PUS7, EFR3B, and NRCAM may be potential biomarkers of glioma. THBS1, CASP8, GRIA2, GRIA4, and ADCYAP1R1 may serve as prognostic markers in glioma.

Glioblastoma (GBM) is a most aggressive primary cancer in brain with poor prognosis. This study aimed to identify novel tumor biomarkers with independent prognostic values in GBMs. The DNA methylation profiles were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus database. Differential methylated genes (DMGs) were screened from recurrent GBM samples using limma package in R software. Functional enrichment analysis was performed to identify major biological processes and signaling pathways. Furthermore, critical DMGs associated with the prognosis of GBM were screened according to univariate and multivariate cox regression analysis. A risk score-based prognostic model was constructed for these DMGs and prediction ability of this model was validated in training and validation data set. In total, 495 DMGs were identified between recurrent samples and disease-free samples, including 356 significantly hypermethylated and 139 hypomethylated genes. Functional and pathway items for these DMGs were mainly related to sensory organ development, neuroactive ligand-receptor interaction, pathways in cancer, etc. Five genes with abnormal methylation level were significantly correlated with prognosis according to survival analysis, such as ALX1, KANK1, NUDT12, SNED1, and SVOP. Finally, the risk model provided an effective ability for prognosis prediction both in training and validation data set. We constructed a novel prognostic model for survival prediction of GBMs. In addition, we identified five DMGs as critical prognostic biomarkers in GBM progression.

Glioma is the most common form of malignant brain cancer with high mortality rate in human. Therefore, finding effective therapeutic strategy and revealing the underlying molecular mechanism is necessary. Ampelopsin (Amp), an effective component of the traditional Chinese herb of Ampelopsis grossedentata, is reported to have important biological properties, including anti-inflammatory, anti-cancer, and anti-oxidant activity; however, its effects on human glioma are poorly understood. Here, the in vitro and in vivo study was performed to investigate the anti-glioma ability of Ampelopsin. Human glioma cell lines of U251 and A172 were treated with Ampelopsin (0, 25, 50, and 100 uM) for 24 h, followed by various analysis. And human glioma xenograft models were established by injecting U251, accompanied with administration of Ampelopsin at 50 and 100 mg/kg to confirm the anti-cancer role of Ampelopsin. We found that Ampelopsin could suppress the glioma cell proliferation by modulating G1 and S phase arrest. Incubation with Ampelopsin led to the activity of Caspase-8, Caspase-9, Caspase-3 and poly (ADP-ribose) polymerases (PARP), indicating that Ampelopsin induced apoptotic response via both intrinsic and extrinsic signaling pathways. Additionally, autophagy was also observed in Ampelopsin-treated cancer cells, which is evidenced by autophagosome formation and LC3B-II accumulation. Ampelopsin-caused cancer cell death was obviously regained by apoptosis inhibitors. Further, Ampelopsin activated c-Jun N-terminal protein kinase (JNK) expression and enhanced reactive oxygen species (ROS) generation. Suppressing JNK markedly ameliorated Ampelopsin-induced apoptosis and autophagy, and ROS scavenger exhibited similar results. In vivo, Ampelopsin inhibited tumor growth and progression in mouse xenograft models. In conclusion, our findings indicated that Ampelopsin led to G1 and S phase arrest, triggered apoptosis and autophagy through potentiating ROS generation and JNK activation in human glioma cells. Thus, Ampelopsin might be a promising candidate against human glioma.

Glioma, an aggressive tumor in brain, presents a very poor prognosis. Emerging evidence has demonstrated that dysfunction of long noncoding RNAs (lncRNAs) is closely related to giloma development. However, the roles of lncRNA BLACAT1 in glioma are not unknown. In this study, we utilized in vitro and in vivo experiments to explore the effects of BLACAT1 on glioma cells. BLACAT1 levels were increased in glioma tissues. Upregulation of BLACAT1 showed poor prognosis. Silencing of BLACAT1 markedly repressed glioma proliferation, migration, and invasion, and suppressed glioma growth in vivo. We also illustrated that BLACAT1 worked as the sponge for miR-605-3p and promoted VASP expression. miR-605-3p was downregulated in glioma and repressed glioma proliferation, migration, and invasion. And VASP is upregulated and contributed to glioma progression. Summarily, this study highlights the important roles of BLACAT1/miR-605-3p/VASP axis in glioma progression.

The great importance of long noncoding RNAs (lncRNAs) has been acknowledged in tumorigenesis gradually. LncRNA LINC01857 is a novel lncRNA and has been reported to promote breast cancer progression. However, the biological roles of LINC01857 in glioma are not explored. In the present research, LINC01857 levels were found to be upregulated in glioma. In addition, LINC01857 expression is negatively correlated with survival rate in glioma patients. Functional investigation revealed that LINC01857 downregulation impaired glioma proliferation and invasiveness. Furthermore, LINC01857 knockdown led to repressed growth of glioma in vivo. We found that LINC01857 could be a sponge for miR-1281 and inhibits its level to upregulate TRIM65 expression. What's more, we showed that miR-1281 mimics also attenuated tumor cell proliferation, migration, and invasion. And rescue assays demonstrated that LINC01857 promotes glioma progression through modulating miR-1281/TRIM65 pathway. Collectively, this study first demonstrated that a novel LINC01857/miR-1281/TRIM65 signaling regulates glioma progression.

Chang Li* Guozhang Hu* Bo Wei Le Wang Naijie Liu 1Department of VIP Unit, China-Japan Union Hospital of Jilin University, Changchun 130031, People’s Republic of China; 2Department of First-aid Medicine, China-Japan Union Hospital of Jilin University, Changchun 130031, People’s Republic of China; 3Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130031, People’s Republic of China; 4Department of Ophthalmology, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China

This study was aimed to identify hub genes associated with the development of glioblastoma (GBM) by conducting a bioinformatic analysis. The raw gene expression data were downloaded from the Gene Expression Omnibus database and The Cancer Genome Atlas project. After the differentially expressed genes (DEGs) were identified, the functional enrichment analysis of DEGs was conducted. Subsequently, the protein-protein interaction (PPI) network, molecular complex detection clusters, and transcriptional factor (TF)-miRNA-target regulatory network were constructed, respectively. Furthermore, the survival analysis of prognostic outcomes and genes was analyzed. In addition, the expression of key genes was validated by quantitative real-time PCR (qRT-PCR) analysis. A total of 884 DEGs, including 418 upregulated and downregulated genes, were identified between GBM and normal samples. The PPI network comprised a set of 3418 pairs involving 751 nodes, and AKT1 and CDK2 were the critical genes in the network. A total of seven clusters were identified, the genes in which were intensively associated with cell cycle, cholinergic synapse, and extracellular matrix (ECM)-receptor interaction. qRT-PCR analysis indicated that AKT1 and CDK2 were significantly upregulated, and NRXN3 and NPTX2 were significantly downregulated in GBM samples. The TF-miRNA-target regulatory networks were built, in which CCNB1, RFC5, microRNA524, and microRNA34b were key regulators. There were 43 genes, including NPTX2 and NRXN3, significantly related to the prognostic outcomes of GBM patients. These crucial genes might be promising options for GBM treatment.

Background: Long noncoding RNAs (lncRNAs) are recognized as key effectors in tumor, including glioma. LINC01494 is an uncharacterized novel lncRNA. In this research, we aimed to investigate the function of LINC01494 in glioma. Methods: Gene relative expression was analyzed by qRT-PCR method. CCK8, colony formation and Transwell assay was used to determine cell proliferation, migration and invasion. Bioinformatics analyses were used to predict the target of LINC01494 and miR-122-5p. Luciferase reporter assay was utilized to validate the interactions between LINC01494 and miR-122-5p or CCNG1 and miR-122-5p. Results: LINC01494 was identified as a significantly upregulated IncRNA in glioma through bioinformatics analysis. Furthermore, LINC01494 upregulation indicated poor prognosis. Meanwhile, in vitro investigation indicated that silencing LINC01494 with siRNAs obviously inhibited the proliferation, cell cycle, migration and invasion of glioma cells. Besides, it is found that LINC01494 expression was negatively correlated with miR-122-5p. We demonstrated that LINC01494 inhibited miR-122-5p to upregulate CCNG1 expression through direct interaction. Rescue assay further demonstrated that LINC01494/miR-122-5p/CCNG1 signaling cascade plays a critical role in regulating glioma cell proliferation, migration and invasion. Conclusion: Taken together, our findings demonstrated the essential function and molecular mechanism of LINC01494 in glioma progression.

A new lead(II)-organic architecture [Pb(HL) (dipyrido[3,2-a:2′,3′-c]phenazine (dppz))](H2O)2 (1) was successfully prepared under hydrothermal conditions by using organic-acid linker 5-((4-carboxyphenoxy)methyl) benzene-1,3-dioic acid (H3L) and N-donor chelating ligand dppz. The as-prepared complex was characterized by single-crystal X-ray structural analysis, powder X-ray diffraction (PXRD), and elemental analyses, which reveals that complex 1 shows a one-dimensional (1D) chain-like structure that is further extended to the 3D supermolecular network through H-bond and π-π interactions. Complex 1 was transformed to the nanoscale regime (ca. 190 nm) by mechanical grinding to yield the nano-1, maintaining its structure and crystallinity. Furthermore, the anticancer activity of the nano-1 toward the human neuroglioma cells (U251, U87, SHG-44, and A172) was evaluated via the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay.

In order to demonstrate the effect of perfusion magnetic resonance (MR) and diffusion tensor magnetic resonance imaging (MRI) in evaluating glioma, arterial spin labeling (ASL) imaging is used to calculate the hemodynamic parameter cerebral blood flow. Diffusion tensor imaging (DTI) is mainly used to analyze the diffusion coefficient of water molecules in the brain, obtaining anisotropic scores, average diffusion coefficients, diffusivity parameters, etc. The separability of these parameters is studied by analyzing the distribution of single parameters, single-model multi-parameters and multi-model multi-parameters. Parameters obtained in this paper are basically consistent with those reported in the previous literature, and the statistical analysis of each parameter is also basically the same as that of predecessors.

To reveal the potential molecular mechanism of glioblastoma multiforme (GBM) and provide the candidate biomarkers for GBM gene therapy. Microarray dataset GSE50161 was obtained from GEO database. The differentially expressed genes (DEGs) were identified between GBM samples and control samples, followed by the module partition analysis based on WGCNA. Then, the pathway and functional enrichment analyses of DEGs were performed. The hub genes were further investigated, followed by the survival analysis and data validation. A total of 1913 DEGs were investigated between two groups, followed by analysis of 5 modules using WGCNA. These DEGs were mainly enriched in functions like inflammatory response. The hub genes including upregulated N-Myc and STAT Interactor (NMI), Capping Actin Protein-Gelsolin Like (CAPG), and Proteasome Subunit Beta 8 (PSMB8) were revealed as potential liquid biopsy molecules for GBM diagnose. Moreover, Nucleolar and Spindle Associated Protein 1 (NUSAP1) and G Protein-Coupled Receptor 65 (GPR65) were outstanding genes in survival analysis. Our results suggested that CPNE6, HAPLN2, CMTM3, NMI, CAPG, and PSMB8 might be used as potential molecules for liquid biopsy of GBM. NUSAP1 and GPR65 might be novel prognostic targets for GBM gene therapy. Furthermore, the upregulated NMI might play an important role in GBM progression via inflammatory response.

Effects of mir-128a on the proliferation and migration of human glioma U251 cells were explored. The constructed mir-128a-shRNA lentivirus vector (infection group) and scramble shRNA (interference group) were transfected into glioma U251 cells, and uninfected U251 cells as control group. The expression level of mir-128a, the ability of proliferation, invasion, apoptosis and migration of cells in each group were detected by RT-qPCR, MTT assay, Transwell migration in vitro, cell wound scratch assay and TUNEL cell apoptosis assay. The expression level of mir-128a in U251 cells of infection group was significantly higher than that in U251 cells of interference group (P<0.05). Τhe expression level of mir-128a in U251 cells of control group was significantly lower than that in U251 cells of infection group (P<0.05). The OD values of infection and control group were lower than that of interference group at 6, 12, 24, 48 and 72 h, and the OD values of infection were lower than that of control group at 6, 12, 24, 48 and 72 h (P<0.05). Compared with infection and control group, the number of membrane-penetrating cells in U251 cells of interference group increased significantly (P<0.05). The apoptosis rate of U251 cells of infection and control group was significantly higher than that of interference group, and the apoptosis rate of infection was significantly higher than that of control group (P<0.05). The migration distance of U251 cells of infection and interference group was significantly larger than that of control group (P<0.05). Τhe migration distance of U251 cells of interference group was significantly larger than that of infection group (P<0.05). mir-128a may play a role similar to anti-oncogene in glioma, inhibiting the ability of proliferation, invasion and migration of glioma cells, and promoting the apoptosis of glioma cells.

This paper explored the application of RNA in cancer gene therapy. Second, the effect of the recombinant plasmid APE1 siRNA on the expression of APE1 protein was observed. In addition, the proliferation of cells in apoptosis and the radiosensitivity of human glioma U251 cells were also discussed. U251 cells were divided into control group, negative group and APE1siRNA group for culturing. There were two holes in each group, and independent experiments were repeated three times. The expression of APE1 protein in U251 cells was detected by Western blot experiments for siRNA transfection. The siRNA cells were transfected, while another group of FAM fluorescent labeled non-sense sequence siRNA was transfected to determine the transfection rate and extract the total protein of the cell. BCA protein assay kit was used for determining the concentration. Meanwhile, 50g sample and SDS-polypropylene diamine gel were prepared. Coomassie blue staining was used to observe the protein electrophoresis, after which the protein on the gel was transferred to the PVDF membrane and then developed in a chemiluminescent detection system with specific antibodies. The β -action test was used as an internal controller, while the optical density scanner was used to detect the gray value of the target strip. The relative expression of target protein was equal to the target band gray value or the same sample reference value of gray. MTT method was used to detect the cell growth curve experiments, while AO or EB method was used to detect the apoptosis rate of glioma cells. SPSS17.0 was used for statistical analysis. The results show that the APE1 siRNA expression plasmid was successfully introduced into human glioma cells by RNA interference, which can reduce the expression of APE1 in cells. It was confirmed that the reduction of APE1 protein could inhibit proliferation and promote the apoptosis of glioma cells. Third, APE1 targeting interference may be an effective gene therapy strategy for human glioma, which can provide an experimental basis for the clinical gene therapy of glioma.

Glioblastoma is the most frequent and most aggressive brain tumour in adults. Temozolomide is an oral chemotherapy drug and one of the major components of chemotherapy regimens used as a treatment of some brain cancers. We examined the tolerance of stem cells isolated from glioma cell line U87 and U251 to temozolomide (TMZ) and explored the effect of PLK1 (Polo like kinase 1) protein expression on TMZ sensibility. In our results, the inhibitory effects of TMZ on glioma cells U87, U251 and its stem cells were confirmed to be dose dependent and time dependent. Compared with glioma cells, the glioma stem cells showed a greater degree of tolerance. As the concentration of TMZ increased, the expression of PLK1 protein increased in U87 cells, CD133(+) U87 stem cells and CD133- U87 cells. The increase range of PLK1 protein was large in CD133(+) U87 stem cells and small in CD133- U87 cells. TMZ treatment in cells with low PLK1 protein expression efficiently suppressed the cell proliferation and sphere formation, while G2/M arrest was strongly induced. What's more, TMZ and PLK1 inhibitor synergize to inhibit glioma growth in vivo. In conclusion, our results suggest that down-regulation of PLK1 protein enhanced the inhibition of TMZ on glioma stem cells, suggesting its clinical value to adverse TMZ resistance in glioma treatment.

Objective To study the role and mechanism of let-7a in cerebral ischemia-reperfusion injury.Methods Rats were divided into Sham group,Control group,anti-let-7a group and GFP group and 6 rats were in each group.Rats in Control group,anti-let-7a group and GFP group were given saline by tail vein,anti-let-7a expression of AAV-9 plasmid or control empty plasmid experiments respectively,and then establish cerebral ischemia and reperfusion model.Infarct volume was examined using TTC staining and apoptosis was evaluated using Tunel staining and caspase-3 detection.The expression of TNF-α and IL-6 in brain tissue was detected by ELISA and qRT-PCR.The regulation of let-7a on the expression of MKP1 was confirmed by Western blot,qRT-PCR and luciferase assay.Results The infarct volume of anti-let-7a group was significantly smaller than that of GFP group and control group,the number of apoptotic cells,the expression of caspase-3,TNF-α and IL-6 in brain tissue were significantly lower than that of GFP group and Control group.Let-7a binds to the MKP1 mRNA 3''UTR end and down-regulates the expression of MKP1 in PC12 cells.Conclusion Knockout of let-7a can inhibit the activation of MAPK signaling pathway by regulating the expression of MKP1,thus excerting the neuroprotective effect against inflammatory reaction and apoptosis after cerebral ischemia-reperfusion.

阿尔茨海默病( AD)是一种由神经系统变性引起的疾病,又叫老年痴呆症. 近年来,我国AD的发病也逐年上升. 目前药物治疗是治疗AD最主要方式之一. 本文对AD发病机制的各种学说与氧化应激的关系进行综述.

The present study aimed to screen potential target genes for the early diagnosis and treatment of early metastatic clear cell renal cell carcinoma (ccRCC) using the microarray data of early metastatic and non-metastatic ccRCC samples. The DNA microarray dataset GSE47352 was downloaded from Gene Expression Omnibus and included 4 early metastatic and 5 non-metastatic ccRCC samples. Differentially expressed genes (DEGs) were screened using the limma package. Then, pheatmap package was used to conduct two-way clustering for the DEGs. Subsequently, MAPPFinder and GenMAPP were employed separately to perform functional and pathway enrichment analysis for the DEGs. Additionally, a protein-protein interaction (PPI) network was constructed using Cytoscape, and small drug molecules were searched using Connectivity map (cmap). In total, 196 upregulated and 163 downregulated genes were identified. DEGs, including JUN, tumor necrosis factor (TNF), Ras homolog family member B (RHOB) and transforming growth factor beta 2 (TGF beta 2) were significantly enriched in the signaling pathway of renal cell carcinoma. Furthermore, nuclear receptor subfamily 4 group A member 1 (NR4A1) was significantly enriched in the mitogen-activated protein kinase signaling pathway; in addition, laminin subunit a (LAMA) 1, LAMA2 and LAMA4 were significantly enriched in extracellular matrix-receptor interaction. JUN (degree=6) had the highest degree in the PPI network. Thapsigargin (score=-0.913) possessed the highest performance in terms of the treatment of early metastatic ccRCC. In the present study, it was discovered that certain DEGs, including JUN, TNF, RHOB, NR4A1, TGF beta 2, LAMA1, LAMA2 and LAMA4 were potential target genes associated with early metastatic ccRCC. In addition, thapsigargin could be used as an efficient small drug molecule for the treatment of early metastatic ccRCC.