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OBJECTIVE: This study aims to analyze CSF dynamics using VOSviewer, CiteSpace, and the Bibliometrix R-package software to identify research hotspots and future directions. METHODS: Search by Web of Science Core Collection Database for related literature on CSF dynamics from 2013 to 2023. Bibliometric and visual analysis of data on number of citations, number of publications, most productive countries and institutions, important authors and journals, time of publication, popular topics and keywords were performed by CiteSpace and VOSviewer. RESULTS AND CONCLUSION: In the field of cerebrospinal fluid (CSF) dynamics, there is an observable upward trend in annual publications. The United States, Japan, and Germany rank as the top three countries in terms of publication output. Copenhagen University, Idaho University, and Zurich University are the leading institutions in terms of research publications.The most frequently published literature over the past decade is "Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep." The most prolific authors in this field are Martin and Bryn. Active authors have formed several stable research teams, indicating collaboration, which could benefit from further enhancement across different teams.Key research keywords such as cerebrospinal fluid, hydrocephalus, dynamics, brain, flow, cerebrospinal-fluid, pressure, CSF flow, MRI highlight the focal areas in CSF dynamics research. These keywords represent both the current focus and forefront of research in this field.
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Background: The incidence of glioma, a prevalent brain malignancy, is increasing, particularly among the elderly population. This study aimed to elucidate the clinical importance of epithelial-mesenchymal transition (EMT) in gliomas and its association with malignancy and prognosis. Background: The incidence of glioma, particularly among elderly individuals, is on the rise. The malignancy of glioma is determined not only by the oncogenic properties of tumor cells but also by the composition of the tumor microenvironment, which includes immune system macrophages. The prevalence of M2-type macrophages typically fosters tumor progression, yet the underlying mechanism remains elusive. Our study explored the clinical importance of epithelial-mesenchymal transition (EMT) in gliomas and its association with malignancy and prognosis. Methods: Our study used the gene set variation analysis (GSVA) algorithm to classify different levels of EMT activation based on the transcriptomic and multi-omics data. Machine learning (ML) and single-cell analysis were integrated into our model for comprehensive analysis. A predictive model was constructed and in vitro experiments were performed to validate our findings. Results: Our study classified 1,641 samples into two clusters based on EMT activation: the EMT-hot group and the EMT-cold group. The EMT-hot group had elevated copy number loss, tumor mutational burden (TMB), and a poorer survival rate. Conversely, the EMT-cold group showed a better survival rate, likely attributed to lower stromal and immune cell scores, as well as decreased expression of human leukocyte antigen-related genes. Driving genes were identified through weighted gene coexpression network analysis (WGCNA) and dimensionality reduction techniques. These genes were then utilized in the construction of a prognostic model using ML and protein-protein interaction (PPI) network analysis. Furthermore, the impact of the core genes identified through single-cell analysis on glioma prognosis was examined. Conclusion: Our research underscores the efficacy of our model in predicting glioma prognosis and elucidates the connection between the M2 macrophages and EMT. Additionally, core genes such as LY96, C1QB, LGALS1, CSPG5, S100A8, and CHGB were identified as pivotal for mediating the occurrence of EMT induced by M2 macrophages.
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OBJECTIVE: Pineal tumors are relatively rare central nervous system lesions with a predilection for the pediatric population. This article aims to explore the clinical effects of neuroendoscopic infratentorial supracerebellar approach for resecting tumors in the pineal area. METHODS: This is a retrospective study that included patients who underwent neuroendoscopic infratentorial supracerebellar approach to resect nine tumors in the pineal area at the Department of Neurosurgery of the Second Hospital of Lanzhou University from December 2017 to October 2023. RESULTS: The results of postoperative MRI revealed that all tumors were resected. Five patients received postoperative radiotherapy, three patients received radiotherapy along with chemotherapy, and one patient received neither radiotherapy nor chemotherapy. The pathological results showed that four patients were diagnosed with germinoma, two patients with teratoma, two patients with mixed germ cell tumors, and one patient with central neurocytoma. After surgery, one patient developed psychiatric symptoms, two patients developed binocular upward vision and diplopia, and one patient developed unstable walking and diplopia. With a follow-up of 1.7-4.8 years, all nine patients lived normally. Furthermore, none of them had tumor recurrence or death. CONCLUSION: The simple neuroendoscopic infratentorial supracerebellar approach has some safety and efficacy. It is suitable for tumors in the pineal region where the disease is mainly located below the Galen vein complex.
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PURPOSE: This study investigated the value of whole tumor apparent diffusion coefficient (ADC) histogram parameters and magnetic resonance imaging (MRI) semantic features in predicting meningioma progesterone receptor (PR) expression. MATERIALS AND METHODS: The imaging, pathological, and clinical data of 53 patients with PR-negative meningiomas and 52 patients with PR-positive meningiomas were retrospectively reviewed. The whole tumor was outlined using Firevoxel software, and the ADC histogram parameters were calculated. The differences in ADC histogram parameters and MRI semantic features were compared between the two groups. The predictive values of parameters for PR expression were assessed using receiver operating characteristic curves. The correlation between whole-tumor ADC histogram parameters and PR expression in meningiomas was also analyzed. RESULTS: Grading was able to predict the PR expression in meningiomas (p = 0.012), though the semantic features of MRI were not (all p > 0.05). The mean, Perc.01, Perc.05, Perc.10, Perc.25, and Perc.50 histogram parameters were able to predict meningioma PR expression (all p < 0.05). The predictive performance of the combined histogram parameters improved, and the combination of grade and histogram parameters provided the optimal predictive value, with an area under the curve of 0.849 (95%CI: 0.766-0.911) and sensitivity, specificity, ACC, PPV, and NPV of 73.08%, 81.13%, 77.14%, 79.20%, and 75.40%, respectively. The mean, Perc.01, Perc.05, Perc.10, Perc.25, and Perc.50 histogram parameters were positively correlated with PR expression (all p < 0.05). CONCLUSION: Whole tumor ADC histogram parameters have additional clinical value in predicting PR expression in meningiomas.
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Imagem de Difusão por Ressonância Magnética , Neoplasias Meníngeas , Meningioma , Receptores de Progesterona , Humanos , Meningioma/diagnóstico por imagem , Meningioma/patologia , Meningioma/metabolismo , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Imagem de Difusão por Ressonância Magnética/métodos , Idoso , Estudos Retrospectivos , Valor Preditivo dos TestesRESUMO
Lipomas, benign tumors originating from the anomalous proliferation of adipocytes, predominantly emerge in regions rich in adipose tissue. However, their presence in the head and neck areas remains rare, constituting approximately 13% of all diagnosed lipoma cases. This study presents a case involving a substantial subcutaneous lipoma located at the posterior neck, measuring about 20 cm × 19 cm × 10 cm. The patient presented with swelling and pain in the back of the neck. And the considerable dimensions of this lipoma significantly impacted the patient's quality of life and aesthetic appearance. Concurrently, the patient exhibited symptoms indicative of degenerative cervical spine disease and cervical disc herniation. After admission, a comprehensive examination, including ultrasound, CT scan, and MRI, was conducted. Given the clinical complexity, the decision for surgical intervention was deemed essential. The surgical strategy entailed a meticulous total excision of the tumor through an incision made in the posterior cross-neck, coupled with the strategic removal of excess skin. To facilitate wound healing, postoperative management included the use of negative pressure drainage. Pathological examination conclusively identified the mass as a lipoma. Postoperative follow-ups indicated successful recovery, as evidenced by the restoration of the neck's aesthetic contour and the complete resolution of the previously observed restrictions in sagittal neck movement.
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Glioma is a malignant tumor of the central nervous system (CNS). Currently, effective treatment options for gliomas are still lacking. Neutrophils, as an important member of the tumor microenvironment (TME), are widely distributed in circulation. Recently, the discovery of cranial-meningeal channels and intracranial lymphatic vessels has provided new insights into the origins of neutrophils in the CNS. Neutrophils in the brain may originate more from the skull and adjacent vertebral bone marrow. They cross the blood-brain barrier (BBB) under the action of chemokines and enter the brain parenchyma, subsequently migrating to the glioma TME and undergoing phenotypic changes upon contact with tumor cells. Under glycolytic metabolism model, neutrophils show complex and dual functions in different stages of cancer progression, including participation in the malignant progression, immune suppression, and anti-tumor effects of gliomas. Additionally, neutrophils in the TME interact with other immune cells, playing a crucial role in cancer immunotherapy. Targeting neutrophils may be a novel generation of immunotherapy and improve the efficacy of cancer treatments. This article reviews the molecular mechanisms of neutrophils infiltrating the central nervous system from the external environment, detailing the origin, functions, classifications, and targeted therapies of neutrophils in the context of glioma.
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Neoplasias Encefálicas , Glioma , Imunoterapia , Neutrófilos , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Glioma/imunologia , Glioma/terapia , Glioma/patologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Imunoterapia/métodos , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Animais , Barreira Hematoencefálica/imunologia , Infiltração de Neutrófilos/imunologiaRESUMO
BACKGROUND: In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive. METHODS: Lentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRTâPCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model. RESULTS: Trem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß, and caused further DNA damage and promoted the apoptosis rate of tumor cells. CONCLUSIONS: Our findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.
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Glioma , Glicoproteínas de Membrana , Microglia , Receptores Imunológicos , Transdução de Sinais , Animais , Humanos , Camundongos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Técnicas de Silenciamento de Genes , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Inflamação/genética , Inflamação/patologia , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , NF-kappa B/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Transdução de Sinais/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genéticaRESUMO
Glioblastoma, previously known as glioblastoma multiform (GBM), is a type of glioma with a high degree of malignancy and rapid growth rate. It is highly dependent on glutamine (Gln) metabolism during proliferation and lags in neoangiogenesis, leading to extensive Gln depletion in the core region of GBM. Gln-derived glutamate is used to synthesize the antioxidant Glutathione (GSH). We demonstrated that GSH levels are also reduced in Gln deficiency, leading to increased reactive oxygen species (ROS) levels. The ROS production induces endoplasmic reticulum (ER) stress, and the proteins in the ER are secreted into the extracellular medium. We collected GBM cell supernatants cultured with or without Gln medium; the core and peripheral regions of human GBM tumor tissues. Proteomic analysis was used to screen out the target-secreted protein CypB. We demonstrated that the extracellular CypB expression is associated with Gln deprivation. Then, we verified that GBM can promote the glycolytic pathway by activating HIF-1α to upregulate the expression of GLUT1 and LDHA. Meanwhile, the DRP1 was activated, increasing mitochondrial fission, thus inhibiting mitochondrial function. To explore the specific mechanism of its regulation, we constructed a si-CD147 knockout model and added human recombinant CypB protein to verify that extracellular CypB influenced the expression of downstream p-AKT through its cell membrane receptor CD147 binding. Moreover, we confirmed that p-AKT could upregulate HIF-1α and DRP1. Finally, we observed that extracellular CypB can bind to the CD147 receptor, activate p-AKT, upregulate HIF-1α and DRP1 in order to promote glycolysis while inhibiting mitochondrial function to adapt to the Gln-deprived microenvironment.
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Glioblastoma , Glutamina , Microambiente Tumoral , Humanos , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/genética , Glutamina/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Glicólise , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Dinâmica Mitocondrial , Animais , Estresse do Retículo Endoplasmático , Glutationa/metabolismo , Proliferação de Células , Mitocôndrias/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 1/genética , DinaminasRESUMO
Sepsis induces profound disruptions in cellular homeostasis, particularly impacting mitochondrial function in cardiovascular and cerebrovascular systems. This study elucidates the regulatory role of the Pyruvate Kinase M2 (PKM2)- Prohibitin 2 (PHB2) axis in mitochondrial quality control during septic challenges and its protective effects against myocardial and cerebral injuries. Employing LPS-induced mouse models, we demonstrate a significant downregulation of PKM2 and PHB2 in both heart and brain tissues post-sepsis, with corresponding impairments in mitochondrial dynamics, including fission, fusion, and mitophagy. Overexpression of PKM2 and PHB2 not only restores mitochondrial function, as evidenced by normalized ATP production and membrane potential but also confers resistance to oxidative stress by mitigating reactive oxygen species generation. These cellular mechanisms translate into substantial in vivo benefits, with transgenic mice overexpressing PKM2 or PHB2 displaying remarkable resistance to sepsis-induced cardiomyocyte and neuronal apoptosis, and organ dysfunction. Our findings highlight the PKM2-PHB2 interaction as a novel therapeutic target for sepsis, providing a foundation for future research into mitochondrial-based interventions to treat this condition. The study's insights into the molecular underpinnings of sepsis-induced organ failure pave the way for potential clinical applications in the management of sepsis and related pathologies.
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Mitocôndrias , Sepse , Animais , Camundongos , Apoptose/genética , Miócitos Cardíacos , Estresse Oxidativo , Sepse/complicações , Sepse/genéticaRESUMO
Gliomas represent the most common and lethal category of primary brain tumors. Bisphenol A (BPA), a widely recognized endocrine disruptor, has been implicated in the progression of cancer. Despite its established links to various cancers, the association between BPA and glioma progression remains to be clearly defined. This study aimed to shed light on the impact of BPA on glioma cell proliferation and overall tumor progression. Our results demonstrate that BPA significantly accelerates glioma cell proliferation in a time- and dose-dependent manner. Furthermore, BPA has been found to enhance the invasive and migratory capabilities of glioma cells, potentially promoting epithelial-mesenchymal transition (EMT) characteristics within these tumors. Employing bioinformatics approaches, we devised a risk assessment model to gauge the potential glioma hazards associated with BPA exposure. Our comprehensive analysis revealed that BPA not only facilitates glioma invasion and migration but also inhibits apoptotic processes. In summary, our study offers valuable insights into the mechanisms by which BPA may promote tumorigenesis in gliomas, contributing to the understanding of its broader implications in oncology.
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Glioma , Humanos , Linhagem Celular Tumoral , Compostos Benzidrílicos/farmacologia , Fenóis/farmacologiaRESUMO
Neurofibromatosis type 1 (NF1) is caused by NF1 gene mutations. Patients with NF1 often have complications with tumors, such as neurofibroma. In order to investigate the pathogenesis of human neurofibroma, a systematic comparison of protein expression levels between Schwann cell-like sNF96.2 cells, which originated from malignant peripheral nerve sheath tumors (MPNST), and normal Schwann cells was performed using 4-D label-free proteomic analysis. In addition, the expression levels and localization of dysregulated proteins were confirmed using a Gene Expression Omnibus (GEO) transcriptomic dataset, Western blot analysis, and immunofluorescence labeling. The effects of SRY-box transcription factor 9 (SOX9) in the neurofibroma and surrounding microenvironment were evaluated in vivo using a tumor transplantation model. The present study observed that SOX9 and procollagen C-endopeptidase enhancer (PCOLCE) were significantly altered. NF1 mutation promoted the nuclear translocation and transcriptional activity of SOX9 in neurofibromas. SOX9 increased collagen VI secretions by enhancing the activation of PCOLCE in neurofibroma cells. These findings might provide new perspectives on the pathophysiological significance of SOX9 in neurofibromas and elucidate a novel molecular mechanism underlying neurofibromas.
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Hypoxia is a prevalent characteristic of numerous neurological disorders including stroke, Alzheimer's disease, and Parkinson's disease. Extracellular vesicles (EVs) are minute particles released by cells that contain diverse biological materials, including proteins, lipids, and nucleic acids. They have been implicated in a range of physiological and pathological processes including intercellular communication, immune responses, and disease progression. EVs are believed to play a pivotal role in modulating the microenvironment of hypoxia-associated neurological diseases. These EVs are capable of transporting hypoxia-inducible factors such as proteins and microRNAs to neighboring or remote cells, thereby influencing their behavior. Furthermore, EVs can traverse the blood-brain barrier, shielding the brain from detrimental substances in the bloodstream. This enables them to deliver their payload directly to the brain cells, potentially intensifying the effects of hypoxia. Nonetheless, the capacity of EVs to breach the blood-brain barrier presents new opportunities for drug delivery. The objective of this study was to elucidate the role of EVs as mediators of information exchange during tissue hypoxia, a pathophysiological process in ischemic stroke and malignant gliomas. We also investigated their involvement in the progression and regression of major diseases of the central nervous system, which are pertinent to the development of therapeutic interventions for neurological disorders.
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Vesículas Extracelulares , Humanos , Vesículas Extracelulares/metabolismo , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/metabolismo , Hipóxia/metabolismo , Barreira Hematoencefálica/metabolismo , AnimaisRESUMO
BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. There are four groups, each with different causal mutations, affected pathways and prognosis. Here, we investigated the role of mitochondria in medulloblastoma and whether there are differences between the different groups. METHODS: We compared the gene expression levels in the four different medulloblastoma groups (MB-WNT, MB-SHH, MB-G3 and MB-G4), with the focus on genes associated with mitochondria. We used several tools including Salmon, Tximeta, DESeq2, BiomaRt, STRING, Ggplot2, EnhancedVolcano, Venny 2.1 and Metscape. RESULTS: A total of 668 genes were differentially expressed and the most abundant genes were associated with cell division pathway followed by modulation of chemical synaptic transmission. We also identified several genes (ABAT, SOX9, ALDH5A, FOXM1, ABL1, NHLH1, NEUROD1 and NEUROD2) known to play vital role in medulloblastoma. Comparative expression analysis revealed OXPHOS complex-associated proteins of mitochondria. The most significantly expressed genes in the MB-SHH and MB-G4 groups were AHCYL1 and SFXN5 while PAICS was significantly upregulated in MB-WNT group. Notably, MB-G3 contained the most downregulated genes from the OXPHOS complexes, except COX6B2 which was strongly upregulated. CONCLUSIONS: We show the importance of mitochondria and compare their role in the four different medulloblastoma groups.
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Neoplasias Cerebelares , Meduloblastoma , Criança , Humanos , Meduloblastoma/diagnóstico , Meduloblastoma/genética , Meduloblastoma/metabolismo , Biomarcadores , Prognóstico , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Fatores de Transcrição Hélice-Alça-Hélice BásicosRESUMO
The imbalance of immune response plays a crucial role in the development of diseases, including glioblastoma. It is essential to comprehend how the innate immune system detects tumors and pathogens. Endosomal and cytoplasmic sensors can identify diverse cancer cell antigens, triggering the production of type I interferon and pro-inflammatory cytokines. This, in turn, stimulates interferon stimulating genes, enhancing the presentation of cancer antigens, and promoting T cell recognition and destruction of cancer cells. While RNA and DNA sensing of tumors and pathogens typically involve different receptors and adapters, their interaction can activate adaptive immune response mechanisms. This review highlights the similarity in RNA and DNA sensing mechanisms in the innate immunity of both tumors and pathogens. The aim is to enhance the anti-tumor innate immune response, identify regions of the tumor that are not responsive to treatment, and explore new targets to improve the response to conventional tumor therapy and immunotherapy.
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Interferon Tipo I , Neoplasias , Humanos , Transdução de Sinais , Imunidade Inata/fisiologia , Imunidade Adaptativa , DNA , RNARESUMO
INTRODUCTION: Despite their recent FDA(Food and Drug Administration) approval, tumour treatment fields (TTFields) have not seen acceptance as part of standard of care (SOC) for the treatment of high-grade gliomas (HGGs). Few studies have reported the clinical effect of simultaneous or sequential use of TTFields with the current SOC. However, whether TTFields are beneficial over the standard treatment remains to be established with a meta-analysis. Therefore, we here performed a systematic review and meta-analysis to understand the benefit of TTFields for patients with HGGs. METHODS AND ANALYSIS: We registered this systematic review with the PROSPERO network (registration number: CRD42023398972) and aimed to follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines in the study. All articles related to TTFields in glioma will be systematically searched for in the following databases since their inception until November 2023: the China National Knowledge Infrastructure, Embase, Cochrane Library, Wanfang Database, China Science Journal Database, China Biomedical Documentation Database, VIP database, Web of Science and PubMed. Article screening and data extraction will be done independently by the authors and cross-checked by two of the authors on completion. The Cochrane risk of bias assessment tool will be used for quality assessment of the included studies. Review Manager V.5.3 (Cochrane Collaboration) will be used to perform the meta-analysis. ETHICS AND DISSEMINATION: Ethical approval is not required because the data used will be obtained from published studies, and there will be no concerns about privacy. The results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023398972.
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Glioma , Estados Unidos , Humanos , Revisões Sistemáticas como Assunto , Metanálise como Assunto , Glioma/terapia , China , Bases de Dados FactuaisRESUMO
The cell cycle, a pivotal regulator of cell proliferation, can be significantly influenced by the phosphatase and tensin homolog (PTEN)/AKT signaling pathway's modulation of cyclin-related proteins. In our study, we discovered the crucial role of EEF1E1 in this process, as it appears to downregulate PTEN expression. Furthermore, our findings affirmed that EEF1E1 modulates downstream cell cycle-related proteins by suppressing the PTEN/AKT pathway. Cell cycle assay results revealed that EEF1E1 downregulation stunted the advancement of glioma cells in both the G1 and S phases. A suite of assays-Cell Counting Kit-8, colony formation, and ethyl-2'-deoxyuridine-substantiated that the EEF1E1 downregulation markedly curtailed glioma proliferation. We further validated this phenomenon through animal studies and coculture experiments on brain slices. Our comprehensive investigation indicates that EEF1E1 knockdown can effectively inhibit the glioma cell proliferation by regulating the cell cycle via the PTEN/AKT signaling pathway. Consequently, EEF1E1 emerges as a potential therapeutic target for glioma treatment, signifying critical clinical implications.
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BACKGROUND: Macropinocytosis is a pathway utilized for the internalization of extracellular fluid, albumin and dissolved molecules. Assessing macropinocytosis has been challenging in the past because the combination of manual acquisition and visual evaluation of images is laborious, making this type of assessment difficult for high-throughput applications. Therefore, there is a need to develop sensitive and specific macropinocytosis evaluation methods. METHODS: This paper proposed a quantitative and time-saving method for macropinocytosis detection based on high-content analysis (HCA). Additionally, cell proliferation was evaluated using CCK8 test. RESULTS: The term "macropinosome index" was defined to estimate macropinocytosis and allow comparisons between different cell lines and treatments. Furthermore, we demonstrated that macropinocytosis can promote glioblastoma (GBM) cell survival under L-glutamine (L-Gln)-deficient conditions that resemble the tumour microenvironment. CONCLUSIONS: HCA represents a novel, nonsubjective and high-throughput assay for macropinocytosis assessment. In addition, L-Gln deprivation increased the macropinosome index in GBM cells, suggesting that this process may be used to design GBM therapies. AVAILABILITY OF DATA AND MATERIALS: The datasets supporting the conclusions of this article are included within the article and its supplementary materials.
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Glioblastoma , Humanos , Glioblastoma/patologia , Pinocitose , Linhagem Celular , Proliferação de Células , Microambiente TumoralRESUMO
Blueberry is a class of berries with high nutritional and economic value but has short shelf life due to its rapid softening at room temperature. This study investigated the effects of plasma-activated water (PAW) treatment on the softening quality and cell wall pectin metabolism of blueberries stored for 10 d at 25 °C after being immersed in PAW for 10 min. PAW was generated by plasma with different times (1 and 2 min), fixed frequency (10 kHz) and fixed voltage (50 kV). The analysis showed that the firmness of PAW-treated fruit significantly increased (P < 0.05) by 36.4% after 10 d storage. PAW treatment controlled the solubilization of pectin from water-insoluble to water-soluble. The activities of cell wall pectin-degrading enzymes like polygalacturonase (PG), ß-galactosidase (ß-Gal) and pectin methylesterase (PME) in PAW-treated blueberries decreased by 15.7%, 18.3%, and 27.9%, respectively, on day 10. After PAW treatment, blueberries also maintained better postharvest quality (firmness, colour, soluble solid content and anthocyanin content) and intact epidermal waxy and cell wall structure. These results suggested that PAW showed great potential for postharvest fresh-keeping of blueberry.
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Mirtilos Azuis (Planta) , Mirtilos Azuis (Planta)/metabolismo , Água/metabolismo , Pectinas/metabolismo , Frutas/metabolismo , Parede Celular/metabolismoRESUMO
BACKGROUND & AIMS: Medulloblastoma (MB) is a primary malignant tumor of the brain. They are categorized as WHO grade IV neoplasms, and mostly occur in children. The traditional therapy for MB is surgery, followed by radiation and chemotherapy, but the clinical outcome is still poor and has a high possibility of recurrence. The mechanism underlying the development of MB should be further investigated to develop novel therapeutic strategies. METHODS: Research has demonstrated that circRNAs contribute to tumorigenesis, but the functional mechanism of circRNAs in MB has not been fully explored and remains vague. The differentially expressed circRNAs between MB and normal cerebellar tissues were analyzed based on the microarray expression profiles to characterize the potential mechanism of circRNAs in MB. RESULTS: The results revealed that circRNA_103128 was highly expressed in MB, and cellular and animal experiments were performed to verify its tumorigenic effect in MB. Furthermore, a bioinformatics analysis and literature review previous literature were performed, confirming miR-129-5p as a target gene downstream of circRNA_103128. In addition, SOX4 was predicted to be a downstream target protein of miR-129-5p. Subsequently, miR-129-5p expression was inhibited, which revealed the regulatory mechanism of circRNA_103128. The latter promotes MB cell growth, migration, and invasion by the sponge effect of miR-129-5p, thereby affecting the expression of SOX4. CONCLUSIONS: This study is the first to systematically demonstrate that circRNA_103128 may play an important regulatory role in MB through a sponge effect with miR-129 -5p, which affects SOX4 expression and regulates tumorigenesis and tumor cell development in MB.
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Neoplasias Cerebelares , Meduloblastoma , MicroRNAs , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Meduloblastoma/genética , Proliferação de Células , Neoplasias Cerebelares/genética , Carcinogênese/genéticaRESUMO
Background: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed. Methods: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). The cases were tabulated by histology and anatomical site. Categorical variables were reported as numbers (percentages). The distribution of tumours by age (0-14, 15-19, 20-39, 40-64, and 65+ years) was analysed. Findings: There were a total of 25,537 brain tumours, foremost among them meningioma (23.63%), followed by tumours of the pituitary (23.42%), and nerve sheath tumours (9.09%). Glioblastoma, the most common and lethal form of primary brain cancer in adults, represented 8.56% of all cases. Of note, 6.48% of the malignant tumours were located in the brain stem. The percentage of malignant brain tumours decreased with increasing age, 24.08% in adults (40+ years), 30.25% in young adults (20-39 years), 35.27% in adolescents (15-19 years), and 49.83% in children (0-14 years). Among the 2107 paediatric patients, the most common sites were ventricle (17.19%), brainstem (14.03%), pituitary and craniopharyngeal duct (13.4%), and cerebellum (12.3%), a distribution that differed from that of the entire cohort. The histology distribution was also unique in children, with glioblastoma much less incident compared to the whole cohort (3% vs. 8.47%, p < 0.01). 58.80% of all patients chose higher-level neurosurgical hospitals outside of their province of residence. The median in-hospital length of stay (LOS) for the various pathologies ranged from 11 to 19 days. Interpretation: The histological and anatomical site distribution of brain tumours in the NBTRC was statistically different in the subgroup of children (0-14 years). Patient choice of pursuing trans-provincial treatment was common and the in-hospital LOS was longer compared to that reported in similar European and American patient populations, which merits further attention. Funding: The National Key Research and Development Program of China (2015BAI12B04, 2013BAI09B03, 2014BAI04B01, and 2021YFF1201104) and Chinese National Natural Science Foundation of China (81971668).