GPR27 expression correlates with prognosis and tumor progression in gliomas.

Backgrounds: Glioma is a highly aggressive type of brain tumor, and its prognosis is still poor despite recent progress in treatment strategies. G protein-coupled receptor 27 (GPR27) is a member of the G protein-coupled receptor family and has been reported to be involved in various cellular processes, including tumor progression. Nevertheless, the clinical potential and tumor-related role of GPR27 in glioma remain unknown. Here we aimed to explore the function and role of GPR27 in gliomas. Methods: In the current study, we evaluated the expression and clinical significance of GPR27 in gliomas using data from The Cancer Genome Atlas (TCGA) datasets. We also conducted cellular experiments to evaluate the functional role of GPR27 in glioma cell growth. Results: We found that GPR27 expression level was closely associated with disease status of glioma. Of note, GPR27 was negatively correlated with WHO grade, with grade IV samples showing the lowest GPR27 levels, while grade II samples showed the highest levels. Patients with IDH mutation or 1p/19q co-deletion exhibited higher GPR27 levels. In addition, lower GPR27 levels were correlated with higher death possibilities. In cellular experiments, we confirmed that GPR27 inhibited glioma cell growth. Conclusions: Our results indicate that GPR27 may function as a potential prognostic biomarker and therapeutic target in gliomas. Further studies are needed to illustrate the signaling mechanism and clinical implications of GPR27 in gliomas.

Transmembrane and Ubiquitin-Like Domain-Containing 1 Promotes Glioma Growth and Indicates Unfavorable Prognosis.

Background: Ubiquitin-related proteins have garnered increasing attention for their roles in tumorigenesis. Transmembrane and ubiquitin-like domain-containing 1 (TMUB1) is a recently discovered protein in the ubiquitin-like domain family, yet its involvement in glioma remains poorly understood. This study is aimed at investigating the functional significance and clinical relevance of TMUB1 in glioma. Methods: We conducted a comprehensive analysis using two cohorts: a retrospective glioma cohort from our hospital and The Cancer Genome Atlas (TCGA) cohort. The mRNA levels of TMUB1 were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Clinical associations of TMUB1 in these cohorts were evaluated using correlation tests, chi-square tests, and survival analyses. Additionally, we performed TMUB1 knockdown in U87 and LN-229 human glioma cell lines, and cellular growth was assessed through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Results: Our results revealed that TMUB1 expression was elevated in glioma tissues compared to normal brain tissues. Notably, lower TMUB1 expression correlated with favorable characteristics such as lower World Health Organization (WHO) grade and 1p/19q codeletion. Moreover, patients with higher TMUB1 levels in glioma tissues exhibited worse prognosis in both TCGA cohort and our retrospective cohort, underscoring its prognostic significance in gliomas. Cellular experiments demonstrated that TMUB1 silencing suppressed the growth of glioma cells. Conclusions: TMUB1 emerges as a novel and clinically relevant prognostic biomarker for gliomas. Targeting TMUB1 holds promise as a potential strategy for glioma treatment. This study contributes valuable insights into the multifaceted role of TMUB1 in glioma pathogenesis and its potential as a diagnostic and therapeutic target.

Clinical Analysis of Ear Congestion after Balloon Eustachian Tuboplasty (BET) with or without Tympanostomy Tube Insertion.

Objective: To explore the clinical analysis of ear congestion after balloon Eustachian tuboplasty (BET) with or without tympanostomy tube insertion. Methods: A total of 35patients (49 affected ears) with ear congestion following BET with or without tympanostomy tube insertion were recruited from the hospitalized patients from January 2015 to December 2017. The score of Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) 15, visual analogue scale (VAS), and Valsalva scores were recorded before and after operation, and the influencing factors of prognosis were analyzed. The duration of follow-up was 1-4 years. Results: All patients showed significantly decreased average preoperative ETDQ-7 score, VAS, and Valsalva score after operation (p < 0.05). The significance of the surgery types, course of disease, severity of tympanic membrane retraction, and tympanogram tracings classification as influencing factors of prognosis did not come up to the statistical standard (p > 0.05). Conclusion: The patients showed relatively stable postoperative conditions after 3 years, and there were variations in the range of ETDQ-7 scores at 5 years postoperatively. Patients with levels I and II tympanic membrane retraction showed more favorable surgical effects. Surgical interventions are required for patients diagnosed with obstructive Eustachian tube dysfunction (ETD) after three months of conservative treatment without satisfactory results.

Prognostic Role of EYA4 in Lower Grade Glioma with IDH1 Mutation and 1p19q Co-Deletion.

BACKGROUND: Eyes absent 4 (EYA4) participates in an important role in various cancers. Patients with low EYA4 expression have significantly favorable prognosis compared with those with high EYA4 expression. However, the expression and role of EYA4 in lower grade glioma (LGG) has not been fully elucidated. METHODS: The R2 and UCSC Xena browser based on data from 284 cases in GSE16011 from Gene Expression Omnibus datasets and 530 cases of patients with LGG in The Cancer Genome Atlas database were extracted for bioinformatic analyses. The EYA4 expression in different subtypes of LGG was detected. Kaplan-Meier survival curves were generated to explore the association between EYA4 expression and overall survival (OS) in both datasets. RESULTS: Patients with LGG with lower EYA4 expression had significantly longer 5- and 10-year OS in 2 datasets (P < 0.001). By matching histological subtypes and gene expression profiles of patients with LGG, oligoastrocytoma and oligodendroglioma groups had lower EYA4 expression and longer OS compared with the astrocytoma group (P < 0.05). Patients with IDH1 mutations and 1p19q co-deletion had longer 5- and 10-year OS (P < 0.001), and EYA4 expression was significantly downregulated in these patients (P < 0.001). CONCLUSIONS: This study suggests that EYA4 can be used as a prognostic marker and provide a potential therapeutic target in patients with LGG with IDH1 mutation and 1p19q co-deletion.

Identification of Hub Genes in Atypical Teratoid/Rhabdoid Tumor by Bioinformatics Analyses.

Atypical teratoid/rhabdoid tumor (ATRT) is a devastating intracranial tumor in children. Currently, its molecular mechanisms cannot be studied effectively because patient samples are limited, and many factors are involved in its pathogenesis. In this study, we analyzed three gene expression profile data sets obtained from the Gene Expression Omnibus (GEO) database to identify genes that participate in ATRT. The datasets were integrated and analyzed using the RobustRankAggreg method to screen for differentially expressed genes (DEGs). We identified 197 DEGs, including 94 downregulated and 103 upregulated genes which were then used for gene set enrichment analysis. The results showed that the downregulated genes were mainly enriched in synaptic vesicle cycle, nicotine addiction, and GABAergic synapse, whereas the upregulated genes were enriched in the cell cycle, p53 signaling pathway, and cellular senescence. Consistent with these results, gene set enrichment analysis showed that E2F targets, G2M checkpoints, and MYC targets were significantly enriched in datasets. Protein-protein interaction (PPI) network revealed that CDK1, CCNA2, BUB1B, CDC20, KIF11, KIF20A, KIF2C, NCAPG, NDC80, NUSAP1, PBK, RRM2, TPX2, TOP2A, and TTK were hub genes. NetworkAnalyst algorithm was used to predict the transcription factor (TF), and the results showed that MYC, SOX2, and KDM5B could regulate these hub genes. In conclusion, the present study brings a new perspective of ATRT pathogenesis and the strategy targeted to cell cycle related gene may be promising treatments for the disease.

Polyphyllin VI Induces Apoptosis and Autophagy via Reactive Oxygen Species Mediated JNK and P38 Activation in Glioma.

BACKGROUND: Polyphyllin VI (PPVI), a bioactive component derived from a traditional Chinese herb Paris polyphylla, exhibits potential antitumor activity against hepatocellular carcinoma, as well as breast and lung cancers. However, its effect on glioma remains unknown. METHODS: Five glioma cell lines (U251, U343, LN229, U87 and HEB) and an animal model were employed in the study. Anti-proliferation effects of PPVI were first determined using CCK-8 cell proliferation and clone formation assays, then reactive oxygen species (ROS), cell cycle progression and apoptosis effects measured by flow cytometry. The effect of PPVI on protein expression was quantified by Western blot analysis. RESULTS: Data showed that PPVI inhibited the proliferation of glioma cell lines by modulating the G2/M phase. Additionally, incubation of cells with PPVI promoted apoptosis, autophagy, increased accumulation of ROS and activated ROS-modulated JNK and p38 pathways. On the other hand, N-acetyl cysteine, a ROS inhibitor, attenuated PPVI-triggered effects. Furthermore, JNK and p38 inhibitors ameliorated PPVI-triggered autophagy and apoptosis in glioma cells. In vivo assays showed that PPVI inhibited tumor growth of U87 cell line in nude mice. CONCLUSION: Overall, these data suggested that PPVI might be an effective therapeutic agent for glioma.

Building addressable libraries: amino acid derived fluorescent linkers.

A new amino acid derived fluorescent linker for attaching molecules to the surface of a microelectrode array has been developed. Molecules to be monitored on an array are attached to the C-terminus of the linker, the N-terminus is then used to attach the linker to the array, and the side chain is used to synthesize a fluorescent tag. The fluorescent group is made with a one-step oxidative cycloaddition reaction starting from a hydroxyindole group. The linker is compatible with site-selective Cu(I)-chemistry on the array, it allows for quality control assessment of the array itself, and it is compatible with the electrochemical impedance experiments used to monitor binding events on the surface of the array.

Building addressable libraries: site-selective use of Pd(0) catalysts on microelectrode arrays.

Site-selective Pd(0)-catalyzed reactions have been developed to functionalize a microelectrode array. Heck, Suzuki, and allylation reactions have all been accomplished. The reactions are compatible with both 1K and 12K arrays and work best when a nonsugar porous reaction layer is used. Suzuki reactions are faster than the Heck reactions and thus require more careful control of the reactions in order to maintain confinement. The allylation reaction requires a different confining agent than the Heck and Suzuki reactions but can be accomplished nicely with quinone as an oxidant for Pd(0).

A new porous reaction layer for developing addressable molecular libraries.

A new diblock copolymer-derived porous reaction layer for microelectrode arrays has been tested for its stability and its compatibility with both site-selective synthesis and electrochemical signaling experiments. The diblock copolymer consisted of a cinnamoyl-substituted polymethacrylate block for attachment to the surface of the array and a bromo-substituted polystyrene block for selective functionalization of the surface proximal to microelectrodes in the array. Site-selective Suzuki, Heck, and Cu(I)-coupling reactions were all performed on the new reaction layer along with electrochemical impedance studies.

Building addressable libraries: site-selective Suzuki reactions on microelectrode arrays.

A site-selective Suzuki reaction has been developed for use on microelectrode arrays. The reaction conditions employed are similar to those used to achieve site-selective Heck reactions. The reaction can be run with either an aryliodide attached to the surface of the array and an arylboronic acid in solution or with an arylboronic acid attached to the surface of the array and an arylbromide in solution. Both allyl acetate and air are effective confining agents for the reaction. The reactions are compatible with arrays containing either 1024 microelectrodes cm(-2) or 12,544 microelectrodes cm(-2).

Efficient synthesis of taurine and structurally diverse substituted taurines from aziridines.

Taurine and substituted taurines were synthesized efficiently from aziridines via ring-opening reaction with thioacetic acid, oxidation with performic acid, and hydrolysis in hydrochloric acid. The current method shows more benefit in purification and efficiency in the preparation of taurine and structurally diverse 2-substituted, 2,2-disubstituted, and 1,2-, 2,2-, and 2,N-alkylene taurines.