Objective: To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment. Methods: Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella. Results: Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced (P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella (P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice (P<0.05). Conclusions: Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.
Calbindins , Cerebellum , DNA-Binding Proteins , Hypoxia , Methyltransferases , Mice, Inbred C57BL , Nerve Tissue Proteins , Purkinje Cells , Animals , Mice , Cerebellum/metabolism , Hypoxia/metabolism , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/genetics , Purkinje Cells/metabolism , Purkinje Cells/pathology , Calbindins/metabolism , Calbindins/genetics , Methyltransferases/metabolism , Methyltransferases/genetics , Glial Fibrillary Acidic Protein/metabolism , Glial Fibrillary Acidic Protein/genetics , Astrocytes/metabolism , Down-Regulation , Methylation , Adenosine/metabolism , Adenosine/analogs & derivatives , Nervous System Malformations/metabolism , Nervous System Malformations/genetics
Castration-resistant prostate cancer (CRPC) threatens the health of men in general and no effective therapeutics currently exists for the treatment of CRPC. It is therefore of great importance to find a novel molecule that can be a biomarker and a therapeutic target for CRPC. First, we found that the serum fibrinogen gamma (FGG) levels in patients with CRPC were significantly higher than those with localized prostate cancer (PCa) through iTRAQ proteomics and ELISA experiments. Immunohistochemistry, quantitative real-time polymerase chain reaction and western blot also showed an increase of FGG expression in CRPC tissues and cells. Then we proved the proliferation, invasion and migration ability of CRPC cells were significantly reduced after FGG knockdown. The number of apoptotic cells increased at least sixfold after FGG silencing, and was observed in conjunction with an upregulation of p53, caspase 3, clea-caspase 3, and Bax, and a downregulation of Bcl2 and survivin. FGG knockdown in DU145 cells resulted in smaller xenografts than control cells in a mouse model. and we established that FGG is modulated by IL-6 which was increased in CRPC patients via phosphorylation of STAT3. The data suggests that FGG may be a potential therapeutic target and prognostic marker for CRPC.
OBJECTIVE: To explore the effect of LncRNA MEG3 in the subarachnoid hemorrhage (SAH) and its underlying mechanism. PATIENTS AND METHODS: The expressions of lncRNA MEG3 in SAH patients and animal model were detected by quantitative real-time PCR (qRT-PCR). After LncRNA MEG3 was overexpressed in neurons by lentivirus, viability and apoptosis abilities were detected by cell counting kit-8 (CCK-8) assay, flow cytometry, and TUNEL assay, respectively. The apoptosis-related genes and Pi3k/Akt pathway-related proteins were further detected by a Western blot. RESULTS: The expressions of lncRNA MEG3 in SAH patients were remarkably higher than normal controls, which were positively correlated with SAH severity. After lncRNA MEG3 overexpression, neuronal cell activity was decreased and cell apoptosis was increased. Moreover, the expressions of Bax, p53, and cleaved Caspase-3 were increased, whereas the expression of Bcl-2 and Pi3k/Akt pathway-related proteins were decreased after lncRNA MEG3 overexpression. CONCLUSIONS: LncRNA MEG3 is up-regulated in SAH, which may promote SAH-induced neuronal cell injury via inhibition of the Pi3k/Akt pathway.
Neurons/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/biosynthesis , Subarachnoid Hemorrhage/metabolism , Aged , Animals , Cells, Cultured , Female , Humans , Male , Middle Aged , Neurons/pathology , Phosphoinositide-3 Kinase Inhibitors , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Rats , Signal Transduction/drug effects , Subarachnoid Hemorrhage/pathology
Benign chondroma affecting the soft tissues is uncommon. This tumour is particularly rare in the neck. We present the first case of soft tissue chondroma arising in the parapharyngeal space of a 20-year-old man with a two-year history of a gradual sensation of a swelling in the pharynx with increasing snoring. The CT and pathological features of this lesion will be discussed. We suggest that a peroral approach should be considered for benign parapharyngeal tumour which has been demonstrated on imaging to be in the anterior parapharyngeal space, especially for tumours that are medial to the pterygoid muscles even though the tumour is a large one.
Chondroma/pathology , Pharyngeal Neoplasms/pathology , Adult , Chondroma/surgery , Humans , Male , Pharyngeal Neoplasms/surgery , Tomography, X-Ray Computed
