Epitranscriptomic abnormalities, which are highly prevalent in primary central nervous system malignancies, have been identified as crucial contributors to the development and progression of gliomas. RNA epitranscriptomic modifications, particularly the reversible modification methylation, have been observed throughout the RNA cycle. Epitranscriptomic modifications, which regulate RNA transcription and translation, have profound biological implications. These modifications are associated with the development of several cancer types. Notably, three main protein types-writers, erasers, and readers, in conjunction with other related proteins, mediate these epitranscriptomic changes. This review primarily focuses on the role of recently identified RNA methylation modifications in gliomas, such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), and N1-methyladenosine (m1A). We delved into their corresponding writers, erasers, readers, and related binding proteins to propose new approaches and prognostic indicators for patients with glioma.
Glioma , Transcriptome , Humans , Methylation , RNA/metabolism , 5-Methylcytosine/metabolism , Glioma/genetics
Astrocytes are implicated in stress-induced neuroinflammatory responses in depression. This paper was to explore the molecular mechanism of the E3 ubiquitin ligase NEDD4L (NEDD4 like E3 ubiquitin protein ligase) in depressed mice by regulating astrocyte activation, and to find a new target for depression. A mouse model of depression was established by CUMS (chronic mild unpredictable stress) in 48 6-week male C57BL/6 mice and injected with sh-NEDD4L vector for testing behavioral and cognitive abilities, histopathological changes, and the number of GFAP-positive cells. The mRNA and protein levels of NEDD4L, PAX6 (paired box 6) and P2X7R (purinergic ligand-gated ion channel 7 receptor) were measured. Inflammation model was established by lipopolysaccharide treatment of mouse astrocyte line C8-D1A and infected with sh-NEDD4L. After CUMS induction, mice showed depression-like symptoms, increased inflammatory infiltration, decreased glial fibrillary acidic protein (GFAP)-positive cells in brain tissue, and increased NEDD4L protein levels. NEDD4L inhibition increased GFAP-positive cells, increased PAX6 protein levels and decreased P2X7R mRNA and protein levels, and decreased inflammatory factor secretion in brain tissue and in vitro cells. PAX6 knockdown or P2X7R overexpression partially reversed the effects of NEDD4L inhibition on astrocyte activation and neuroinflammation. To conclude, highly-expressed NEDD4L in depression-like mouse brain inhibits astrocyte activation and exacerbates neuroinflammation by ubiquitinating PAX6 and promoting P2X7R level.
Objective: Although endovascular recanalization is considered a more effective treatment for chronic internal carotid artery occlusion (CICAO), the success rate of complex CICAO remains inadequate. We present hybrid surgery (carotid endarterectomy combined with carotid stenting) for complex CICAO and explore the influential factors and effects of hybrid surgery recanalization. Methods: We retrospectively analyzed the clinical, imaging, and follow-up data of 22 patients with complex CICAO treated by hybrid surgery at the Zhongnan Hospital of Wuhan University from December 2016 to December 2020. We also summarize the technical points related to hybrid surgery recanalization. Results: A total of 22 patients with complex CICAO underwent hybrid surgery recanalization. There were no postoperative deaths in all patients after hybrid surgery recanalization. Nineteen patients successfully underwent recanalization with a success rate of 86.4% and three cases with a failure rate of 13.6%. Patients were divided into success and failure groups. Significantly different radiographic classification of lesions was observed between the success group and the failure group (P = 0.019). The rates of CICAO with reverse ophthalmic artery blood flow in the internal carotid artery (ICA) preoperatively were 94.7% in the success group and 33.3% in the failure group (P = 0.038). Three cases of hybrid surgery recanalization failure were transferred for EC-IC bypass and had good neurological recovery. Postoperative average KPS scores of the 19 patients were improved compared to the preoperative ones (P < 0.001). Conclusion: Hybrid surgery for complex CICAO is safe and effective with a high recanalization rate. The recanalization rate is related to whether the occluded segment surpasses the ophthalmic artery.
BACKGROUND: We report a case of 39-year-old male patient with an unruptured middle cerebral artery aneurysm associated with moyamoya disease (MMD) treated by surgical clipping combined with encephalo-duro-myo-synangiosis surgery. CASE DESCRIPTION: A 39-year-old male patient with a history of intraventricular hemorrhage was admitted to our hospital. Preoperative digital subtraction angiography (DSA) showed the aneurysm, arising from a collateral branch of the right middle cerebral artery (RMCA), had an extremely thin neck. Also present were an occlusion of the RMCA main trunk, and moyamoya vessels. Microsurgical aneurysm clipping was performed for the aneurysm, while encephalo-duro-myo-synangiosis was performed for ipsilateral MMD. At the 4-month follow-up, the patient had recovered well and DSA indicated improved cerebral perfusion with no de novo aneurysms. CONCLUSIONS: For ipsilateral moyamoya disease accompanied with intracranial aneurysm (IA), simultaneous surgery combining microsurgical clipping and encephalo-duro-myo-synangiosis can be a good treatment option.
Background: Tumor necrosis factor (TNF) is an inflammatory cytokine that can coordinate tissue homeostasis by co-regulating the production of cytokines, cell survival, or death. It widely expresses in various tumor tissues and correlates with the malignant clinical features of patients. As an important inflammatory factor, the role of TNFα is involved in all steps of tumorigenesis and development, including cell transformation, survival, proliferation, invasion and metastasis. Recent research has showed that long non-coding RNAs (lncRNAs), defined as RNA transcripts >200 nucleotides that do not encode a protein, influence numerous cellular processes. However, little is known about the genomic profile of TNF pathway related-lncRNAs in GBM. This study investigated the molecular mechanism of TNF related-lncRNAs and their immune characteristics in glioblastoma multiforme (GBM) patients. Methods: To identify TNF associations in GBM patients, we performed bioinformatics analysis of public databases - The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). The ConsensusClusterPlus, CIBERSORT, Estimate, GSVA and TIDE and first-order bias correlation and so on approaches were conducted to comprehensively characterize and compare differences among TNF-related subtypes. Results: Based on the comprehensive analysis of TNF-related lncRNAs expression profiles, we constructed six TNF-related lncRNAs (C1RL-AS1, LINC00968, MIR155HG, CPB2-AS1, LINC00906, and WDR11-AS1) risk signature to determine the role of TNF-related lncRNAs in GBM. This signature could divide GBM patients into subtypes with distinct clinical and immune characteristics and prognoses. We identified three molecular subtypes (C1, C2, and C3), with C2 showing the best prognosis; otherwise, C3 showing the worst prognosis. Moreover, we assessed the prognostic value, immune infiltration, immune checkpoints, chemokines cytokines and enrichment analysis of this signature in GBM. The TNF-related lncRNA signature was tightly associated with the regulation of tumor immune therapy and could serve as an independent prognostic biomarker in GBM. Conclusion: This analysis provides a comprehensive understanding of the role of TNF-related characters, which may improve the clinical outcome of GBM patients.
A method for the acyclic diene metathesis polymerization of semiaromatic amides is described. The procedure uses second-generation Grubbs' catalyst and N-cyclohexyl-2-pyrrolidone (CHP), a high boiling, polar solvent capable of solubilizing both monomer and polymer. The addition of methanol to the reaction was found to significantly increase polymer molar mass although the role of the alcohol is currently not understood. Hydrogenation with hydrogen gas and Wilkinson's catalyst resulted in near-quantitative saturation. All polymers synthesized here exhibit a hierarchical semicrystalline morphology driven by ordering of aromatic amide groups via strong nonbonded interactions. Furthermore, the melting points can be tuned over a >100 °C range by precise substitution at just one of the backbone positions on each mer (<5% of the total).
Objective: Although balloon-assisted techniques are valuable in aneurysm clipping, repeated angiography and fluoroscopy are required to understand the location and shape of the balloon. This study investigated the value of visualization balloon occlusion-assisted techniques in aneurysm hybridization procedures. Methods: We propose a visualization balloon technique that injects methylene blue into the balloon, allowing it to be well visualized under a microscope without repeated angiography. This study retrospects the medical records of 17 large or giant paraclinoid aneurysms treated by a visualization balloon occlusion-assisted technique in a hybrid operating room. Intraoperative surgical techniques, postoperative complications, and immediate and long-term angiographic findings are highlighted. Results: All 17 patients had safe and successful aneurysm clipping surgery with complete angiographic occlusion. Under the microscope, the balloon injected with methylene blue is visible through the arterial wall. The position and shape of the balloon can be monitored in real time without repeated angiography and fluoroscopic guidance. Two cases of intraoperative visualization balloon shift and slip into the aneurysm cavity were detected in time, and there were no cases of balloon misclipping or difficult removal. Of 17 patients, four patients (23.5%) experienced short-term complications, including pulmonary infection (11.8%), abducens nerve paralysis (5.9%), and thalamus hemorrhage (5.9%). The rate of vision recovery among patients with previous visual deficits was 70% (7 of 10 patients). The mean follow-up duration was 32.76 months. No aneurysms or neurological deficits recurred among all patients who completed the follow-up. Conclusion: Our study indicates that microsurgical clipping with the visualization balloon occlusion-assisted technique seems to be a safe and effective method for patients with large or giant paraclinoid aneurysms to reduce the surgical difficulty and simplify the operation process of microsurgical treatment alone.
Aneurysm, Ruptured , Embolization, Therapeutic , Endovascular Procedures , Intracranial Aneurysm , Subarachnoid Hemorrhage , Humans , Intracranial Aneurysm/surgery , Microsurgery , Subarachnoid Hemorrhage/surgery , Aneurysm, Ruptured/surgery , Costs and Cost Analysis , Treatment Outcome , Retrospective Studies
Background: Glioma is the most common primary tumor of the central nervous system (CNS). Centromere protein A (CENPA) plays an essential role in ensuring that mitosis proceeds normally. The effect of CENPA on glioma is rarely reported. However, the current study aims to explore whether aberrant CENPA expression promotes glioma progression and the potential mechanisms involved. Methods: The GEPIA website, The Cancer Genome Atlas, and the Gene Expression Omnibus (GEO) were used to assess the expression of CENPA in glioma. The results were validated by real-time quantitative polymerase chain reaction and immunohistochemical staining of clinical samples. The relationship between the expression and prognostic value of the CENPA gene in glioma was investigated by Kaplan-Meier (KM) survival analysis with RNA-seq and clinical profiles downloaded from the Chinese Glioma Genome Atlas (CGGA) and UCSC Xena. The association between CENPA and clinical characteristics was also evaluated. Cell Counting Kit-8 (CCK8) assay, wound healing assay using two glioma cell lines, gene set enrichment analysis (GSEA), KEGG and gene ontology (GO) enrichment analysis, immune infiltration analysis, temozolomide (TMZ) sensitivity analysis, and single-cell sequence analysis were performed to explore the underlying mechanisms of high CENPA expression and its effect on glioma development. Finally, we performed a Cox analysis based on the expression of CENPA to predict patient prognosis. Results: CENPA was significantly upregulated in glioma tissue samples and correlated with patient prognosis. Moreover, the downregulation of CENPA inhibited the migration and proliferation of glioma cells. In addition, the expression level of CENPA was significantly correlated with the grade, primary-recurrent-secondary (PRS) type, IDH mutation status, and 1p19q codeletion status. Furthermore, CENPA could serve as an independent prognostic factor for glioma that mainly interferes with the normal progression of mitosis and regulates the tumor immune microenvironment favoring glioma development. Conclusion: CENPA may act as a prognostic factor in patients with glioma and provide a novel target for the treatment of gliomas.
The primitive trigeminal artery (PTA), an abnormal carotid-basilar anastomosis, forms the vascular anomaly connection between the internal carotid artery and vertebrobasilar system. Rarely, PTA can be complicated by several other cerebrovascular disease, including arteriovenous malformations (AVMs), intracranial aneurysms, moyamoya disease, and carotid-cavernous malformations. Herein, we reported a rare case of PTA combined with an AVM in a male patient. The patient was a 28-year-old male with epileptic seizures at the onset of symptoms. Magnetic resonance imaging showed abnormal signal foci and localized softening foci formation with gliosis in the right parietal temporal lobe. Furthermore, using a digital subtraction angiogram (DSA), it was found that an abnormal carotid-basilar anastomosis had developed through a PTA originating from the cavernous portion of the right internal carotid artery (ICA) and a large AVM on the surface of the right carotid artery. The lesion of AVM tightly developed and draining into superior sagittal sinus. A hybrid operating room was used for the surgery. The main feeding arteries of the AVM originating from three major arteries, including the right middle cerebral artery, the right anterior cerebral artery, and the right posterior cerebral artery, were clipped and subsequently, then the AVM was thoroughly removed. The intraoperative DSA showed that the AVM had been resected completely. Postoperative pathological examination of the resected specimen indicated the presence of an AVM. The patient recovered well after surgery and has been symptom-free for more than 3 months. In summary, the pathogenesis of the coexistence of PTA and AVM remains unknown. As highlighted in this case report, hybrid surgery can be used to remove AVMs and can improve the patients' prognosis. To our best knowledge, this is the first case in the literature of successful AVM treatment using hybrid surgery.
Sodium (Na+) and potassium (K+) homeostasis is essential for plant survival in saline soils. A member of the High-Affinity K+ Transporter (HKT) family in rice (Oryza sativa), OsHKT1;1, is a vital regulator of Na+ exclusion from shoots and is bound by a MYB transcription factor (OsMYBc). Here, we generated transgenic rice lines in the oshkt1;1 mutant background for genetic complementation using genomic OsHKT1;1 containing a native (Com) or mutated (mCom) promoter that cannot be bound by OsMYBc. In contrast to wild-type (WT) or Com lines, the mCom lines were not able to recover the salt-sensitive phenotype of oshkt1;1. The OsMYBc-overexpressing plants were more tolerant to salt stress than WT plants. A yeast two-hybrid screen using the OsMYBc N-terminus as bait identified a rice MYBc stress-related RING finger protein (OsMSRFP). OsMSRFP is an active E3 ligase that ubiquitinated OsMYBc in vitro and mediated 26S proteasome-mediated degradation of OsMYBc under semi-in vitro and in vivo conditions. OsMSRFP attenuated OsMYBc-mediated OsHKT1;1 expression, and knockout of OsMSRFP led to rice salt tolerance. These findings uncover a regulatory mechanism of salt response that fine-tunes OsHKT1;1 transcription by ubiquitination of OsMYBc.
Cation Transport Proteins , Oryza , Plant Proteins , Plants, Genetically Modified , Salt Stress , Symporters , Transcription Factors , Ubiquitin-Protein Ligases , Cation Transport Proteins/genetics , Cation Transport Proteins/metabolism , Gene Expression Regulation, Plant , Oryza/genetics , Oryza/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , Potassium/metabolism , Salt Stress/genetics , Sodium/metabolism , Symporters/genetics , Symporters/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Ubiquitin-Protein Ligases/metabolism
