Invasion and migration of glioblastoma multiforme (GBM) is a multistep process and an important phenotype that causes this disease to invade surrounding tissues in the brain. Recent studies have highlighted that miRNAs play a pivotal role in controlling GBM cell plasticity. In this report, we used wound healing and transwell assays to identify a novel role of miR-139-5p in inhibition of GBM cell migration and invasion. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-139-5p inhibited expression of ZEB1 and ZEB2, which are master regulators of tumor metastasis. MiR-139-5p specifically interacts with the 3'-UTR regions of ZEB1 and ZEB2, attenuating their expression in GBM cells. To corroborate this finding, we rescued ZEB1 and ZEB2 expression and found partial but significant increases in miR-139-5p-suppressed invasion of GBM cells. The biological relevance of our study was validated by analyzing levels of miR-139-5p in GBM tissue. We found that its expression significantly downregulated compared to normal tissue and shorter overall survival rates in patients with lower miR-139-5p expression. These results confirm that miR-139-5p suppresses GBM migration and invasion and highlight its potential as a biomarker and therapeutic target for treating GBM.
Diploid gynogenetic fry of rainbow trout, Salmo guirdnui, were produced by treating eggs activated by UV-irradiated sperm with hydrostatic pressure. Treatments for 10 min at 40 min after activation with 55 000 kPa (8000 psi) pressure resulted in high hatching rates and yields of heterozygous diploid gynogenomes of up to 8 1 Yo. Attempts to produce homozygous diploid gynogenomes by the suppression of the first mitotic division of the eggs failed.Ether treatment alone did not induce diploid gynogenesis.
PurposeDiscuss the clinical efficacy of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal Cerebellar Tonsillar Herniation and reconstruction of Cisterna magna.Methods130 Chiari malformation type I with syringomyelia patients, divided into treatment group, literature group and control group, were collected to be treated under the monitoring of ultrasound in the surgery.Results6 months after operation, the lesions were decreased or disappeared, the symptoms were relieved obviously. According to MRI and Mimics 17.0 software, the volumes of Cisterna magna increased distinctly (P < 0.001), the proportions of brain in foramen magnum region were decreased (P < 0.001). Assessed by CCOS scale and Tator methods, the improvement rates of treatment group were 97.7% and 94.6%, the literature group and control group were 82.2% and 77.8%, respectively.ConclusionThe efficacy of Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal Cerebellar Tonsillar Herniation and reconstruction of Cisterna magna is remarkable, and the complications are fewer. This surgery emphasizes recovery of tonsil of cerebellum and reconstruction of Cisterna magna and the circulation path of cerebrospinal fluid, which is a safe and efficient treatment.
Human glioma is a highly fatal tumor with a significant feature of immune suppression. The functions of PD-L1 refer to co-simulation and immune regulation. To investigate expression and functional activity of PD-L1 in human glioma cell in vivo and in vitro. Expressions of PD-L1mRNA and protein in the human glioma cell line were analyzed with quantitative RT-PCR and flow cytometer; and then expression of PD-L1 in tissue specimens of 10 glioma patients was treated with immunohistochemical analysis; glioma cell and allogeneic CD4 and CD8 T cells were co-cultured, and cytokine IFN-γ, IL-2 and IL-10 in cultured supernatant fluid were determined with ELISA; upon blocking the interaction between glioma cell and the immune cell with PD-L1 monoclonal antibody (5H1), surface markers on immune cells were analyzed using flow cytometer. ll human glioma cell lines constitutively expressed PD-L1, and IFN-γ induced glioma cell to highly express PD-L1. It was shown through immunohistochemical analysis that glioma specimen expressed PD-L1, while expression of PD-L1 was not observed in normal tissue and normal human brain near the tumor location. The release of IFN-γ and IL-2 was inhibited, while IL-10 was increased slightly. Glioma cell may escape from immune recognition and injury with the help of PD-L1, which is a significant pathogenic mechanism of glioma.
In this study, we investigated the therapeutic effects of Human Mesenchymal Stem Cells (hMSCs) cultured by hanging drop and conventional culturing methods on cerebellar repair in hypoxic-ischemic (HI) brain injured mice. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to analyze the expression levels of three stemness genes, Oct4, Sox2 and Nanog, and the migration related gene CXCR4. MSC prepared by hanging drop or conventional techniques were administered intranasally to nine day old mice, and analyzed by MRI at day 28. Results indicate that the MSCs, especially the hanging drop cultured MSCs, significantly improved the mice’s cerebellar damage repair. MSCs derived from the hanging drop culture were smaller than those from the conventional culture. The gene expression levels were significantly increased for the MSCs derived from the hanging drop culture. The mechanism might relate to the fact that the hanging drop cultured MSCs can be kept in an undifferentiated state, resulting in its higher expression level of migration receptor of CXCR4.
Diploid gynogenesis in rainbow trout eggs was induced by a heat shock applied after fertilization with UV irradiated sperm. Survivals were high when the heat treatment was given soon after fertilization at times corresponding to the completion of egg meiosis but were low at all other times. Increases in survival occurred, however, when the heat treatment was given at 4 h 30 min and 5 h after fertilization, with an incubation temperature of 10" C, and at 9 h after fertilization, with an incubation temperature of 5" C. Electrophoretic analysis at three enzyme loci demonstrated a significant increase in homozygous offspring from eggs given these later heat treatments when compared to offspring from eggs treated between 40 and 70 min after fertilization, again with an incubation temperature of lo" C. There was still a significant frequency of heterozygotes in these groups, however, probably of spontaneous origin via diploidization during meiosis. No tetraploid alevins were observed after normal fertilization and attempted suppression of first mitosis.
Triploid rainbow trout were produced by hydrostatic pressure applied to eggs 40 min after fertilization. Treatment for 10 rnin with or without exposure to 2% ether produced high hatching rates. Nuclear measurements from serial section of 40-day-old fry and from blood smears of 5-month-old juveniles showed that the proportion of triploid individuals was 80-90°/o. Ether treatment alone did not induce triploidy. Attempts to produce tetraploids by hydrostatic pressure treatment of eggs at 8 h after fertilization failed. Parallel results were also obtained with heat shock.
N1-methyladenosine (m1A) is ubiquitous in eukaryotic RNA and regulates mRNA translation. However, little is known about its regulatory role in glioma. Here, we identified 4 m1A modification-related patterns based on m1A regulators in the TCGA (The Cancer Genome Atlas) and CGGA (Chinese Glioma Genome Atlas) cohorts. The differences in survival prognosis between different clusters were striking. In addition, stemness, genomic heterogeneity, tumor microenvironment (TME), and immune cell infiltration were also significantly different between the poor and best prognostic clusters. To reveal the underlying mechanism, differentially expressed genes (DEGs) between the poor and best prognostic clusters were identified, and then were integrated for weighted correlation network analysis (WGCNA). After Univariate Cox-LASSO-Multivariate Cox analyses, DEGs PLEK2 and ABCC3 were screened as the risk-hub genes and were selected to construct an m1A-related signature. Moreover, ABCC3 exacerbated glioma proliferation and was associated with temozolomide (TMZ) resistance. Overall, our study provided new insights into the function and potential therapeutic role of m1A in glioma.
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