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INTRODUCTION: Glioblastoma multiforme (GBM) poses a significant challenge in terms of treatment due to its high malignancy, necessitating the identification of additional molecular targets. VSIG4, an oncogenic gene participates in tumor growth and migration in various cancer types. Nevertheless, the precise process through which VSIG4 facilitates the malignant progression of glioma remains to be elucidated. OBJECTIVES: This research aims to explore the function and molecular mechanism involving VSIG4 in the malignant progression of glioma. METHODS: The amount of VSIG4 was measured using qPCR, western blotting, and immunohistochemistry. Lentivirus infections were applied for upregulating or downregulating molecules within glioma cells. The incorporation of 5-ethynyl-20-deoxyuridine, Transwell, cell counting kit-8, and clone formation experiments, were applied to assess the biological functions of molecules on glioma cells. Dual luciferase reporter gene, RNA immunoprecipitation, and chromatin immunoprecipitation assays were used to explore the functional relationship among relevant molecules. RESULTS: The upregulation of VSIG4 was observed in GBM tissues, indicating an adverse prognosis. Silencing VSIG4 in glioma cells resulted in a decrease in cell viability, invasion, proliferation, and tumorigenesis, an increase in cell apoptosis, and a stagnation in the cell cycle progression at the G0/G1 phase. Mechanistically, SPI1-mediated upregulation of VSIG4 expression led to binding between VSIG4 and THBS1 protein, ultimately facilitating the malignant progression of glioma cells through the activation of the PI3K/AKT pathway. The inhibited proliferative and invasive capabilities of glioma cells were reversed by overexpressing THBS1 following the knockdown of VSIG4. CONCLUSION: Our findings provide evidence for the role of VSIG4 as an oncogene and reveal the previously unidentified contribution of the SPI1/VSIG4/THBS1 axis in the malignant progression of glioma. This signaling cascade enhances tumor growth and invasion by modulating the PI3K/AKT pathway. VSIG4 as a potential biomarker may be a viable strategy in the development of tailored molecular therapies for GBM.
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BACKGROUND: Anaemia is a severe and common complication in patients with aneurysmal subarachnoid haemorrhage (aSAH). Early intervention for at-risk patients before anaemia occurs is indicated as potentially beneficial, but no validated method synthesises patients' complicated clinical features into an instrument. The purpose of the current study was to develop and externally validate a nomogram that predicted postacute phase anaemia after aSAH. METHODS: We developed a novel nomogram for aSAH patients to predict postacute phase anaemia (3 days after occurrence of aSAH, prior to discharge) on the basis of demographic information, imaging, type of treatment, aneurysm features, blood tests and clinical characteristics. We designed the model from a development cohort and tested the nomogram in external and prospective validation cohorts. We included 456 aSAH patients from The First Affiliated Hospital for the development, 220 from Sanmen People's Hospital for external validation and a prospective validation cohort that included 13 patients from Hangzhou Red Cross Hospital. We assessed the performance of the nomogram via concordance statistics and evaluated the calibration of predicted anaemia outcome with observed anaemia occurrence. RESULTS: Variables included in the nomogram were age, treatment method (open surgery or endovascular therapy), baseline haemoglobin level, fasting blood glucose level, systemic inflammatory response syndrome score on admission, Glasgow Coma Scale score, aneurysm size, prothrombin time and heart rate. In the validation cohort, the model for prediction of postacute phase anaemia had a c-statistic of 0.910, with satisfactory calibration (judged by eye) for the predicted and reported anaemia outcome. Among forward-looking forecasts, our predictive model achieved an 84% success rate, which showed that it has some clinical practicability. CONCLUSIONS: The developed and validated nomogram can be used to calculate individualised anaemia risk and has the potential to serve as a practical tool for clinicians in devising improved treatment strategies for aSAH.
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Anemia , Nomogramas , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Anemia/etiología , Anemia/diagnóstico , Anemia/sangre , Estudios Prospectivos , Anciano , Adulto , Aneurisma Intracraneal/complicacionesRESUMEN
Gamma knife radiosurgery (GKRS) is recommended as the first-line treatment for brain metastases of lung adenocarcinoma (LUAD) in many guidelines, but its specific mechanism is unclear. We aimed to study the changes in the proteome of brain metastases of LUAD in response to the hyperacute phase of GKRS and further explore the mechanism of differentially expressed proteins (DEPs). Cancer tissues were collected from a clinical trial for neoadjuvant stereotactic radiosurgery before surgical resection of large brain metastases (ChiCTR2000038995). Five brain metastasis tissues of LUAD were collected within 24 h after GKRS. Five brain metastasis tissues without radiotherapy were collected as control samples. Proteomics analysis showed that 163 proteins were upregulated and 25 proteins were downregulated. GO and KEGG enrichment analyses showed that the DEPs were closely related to ribosomes. Fifty-three of 70 ribosomal proteins were significantly overexpressed, while none of them were underexpressed. The risk score constructed from 7 upregulated ribosomal proteins (RPL4, RPS19, RPS16, RPLP0, RPS2, RPS26 and RPS25) was an independent risk factor for the survival time of LUAD patients. Overexpression of ribosomal proteins may represent a desperate response to lethal radiotherapy. We propose that targeted inhibition of these ribosomal proteins may enhance the efficacy of GKRS.
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Adenocarcinoma del Pulmón , Neoplasias Encefálicas , Neoplasias Pulmonares , Proteómica , Radiocirugia , Proteínas Ribosómicas , Humanos , Proteínas Ribosómicas/metabolismo , Radiocirugia/métodos , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Masculino , Femenino , Proteómica/métodos , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma del Pulmón/radioterapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Persona de Mediana Edad , Anciano , Regulación Neoplásica de la Expresión Génica , Proteoma/metabolismoRESUMEN
Subarachnoid hemorrhage (SAH) is a serious hemorrhagic event with high mortality and morbidity. Multiple injurious events produced by SAH can lead to a series of pathophysiologic processes in the hypothalamus that can severely impact patients' life. These pathophysiologic processes usually result in physiologic derangements and dysfunction of the brain and multiple organs. This dysfunction involved multiple dimensions of the genome and metabolome. In our study, we induced the SAH model in rats to obtain hypothalamic tissue and serum. The samples were subsequently analyzed by transcriptomics and metabolomics. Next, the functional enrichment analysis of the differentially expressed genes and metabolites were performed by GO and KEGG pathway analysis. Through transcriptomic analysis of hypothalamus samples, 263 up-regulated differential genes, and 207 down-regulated differential genes were identified in SAH groups compared to Sham groups. In the KEGG pathway analysis, a large number of differential genes were found to be enriched in IL-17 signaling pathway, PI3K-Akt signaling pathway, and bile secretion. Liquid chromatography-mass spectrometry metabolomics technology was conducted on the serum of SAH rats and identified 11 up-regulated and 26 down-regulated metabolites in positive ion model, and 1 up-regulated and 10 down-regulated metabolites in negative ion model. KEGG pathways analysis showed that differentially expressed metabolites were mainly enriched in pathways of bile secretion and primary bile acid biosynthesis. We systematically depicted the neuro- and metabolism-related biomolecular changes occurring in the hypothalamus after SAH by performing transcriptomics and metabolomics studies. These biomolecular changes may provide new insights into hypothalamus-induced metabolic changes and gene expression after SAH.
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Hipotálamo , Metabolómica , Ratas Sprague-Dawley , Hemorragia Subaracnoidea , Transcriptoma , Animales , Hemorragia Subaracnoidea/metabolismo , Hemorragia Subaracnoidea/genética , Ratas , Hipotálamo/metabolismo , Masculino , Perfilación de la Expresión Génica , MetabolomaRESUMEN
Rapid advances in nanomedicine have enabled potential applications in cancer therapy. The enhanced permeability and retention (EPR) effect is the primary rationale for the passive targeting of nanoparticles in oncology. However, growing evidence indicates that the accumulation of nanomaterials via the EPR effect could be more efficient. Inspired by our clinical observation of the Gap Junction connecpion between folliculostellate cells and pituitary adenoma cells, we designed a novel drug delivery system that targets tumours by coating folliculostellate cell (FS) membranes onto PLGA nanoparticles (NPs). The resulting FSNPs, inheriting membrane proteins from the folliculostellate cell membrane, significantly enhanced the EPR effect compared to nanoparticles without cancer cell membranes. We further demonstrated that mitotane encapsulation improved the therapeutic efficacy of mitotane in both heterotopic and orthotopic pituitary adenoma models. Owing to its significant efficacy, our FS cell membrane-coated nanoplatforms has the potential to be translated into clinical applications for the treatment of invasive pituitary adenoma.
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This study aimed to treat diabetic cerebral ischemia-reperfusion injury (CI/RI) by affecting blood brain barrier (BBB) permeability and integrity. The CI/RI model in DM mice and a high glucose (HG) treated oxygen and glucose deprivation/reoxygenation (OGD/R) brain endothelial cell model were established for the study. Evans blue (EB) staining was used to evaluate the permeability of BBB in vivo. TTC staining was used to analyze cerebral infarction. The location and expression of tribbles homolog 3 (TRIB3) in endothelial cells were detected by immunofluorescence. Western blotting was used to detect the protein expressions of TRIB3, tight junction molecules, adhesion molecules, phosphorylated protein kinase B (p-AKT) and AKT. The levels of pro-inflammatory cytokines were detected by qRT-PCR. Trans-epithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran were used to measure vascular permeability in vitro. TRIB3 ubiquitination and acetylation levels were detected. Acetyltransferase bound to TRIB3 were identified by immunoprecipitation. TRIB3 was localized in cerebral endothelial cells and was highly expressed in diabetic CI/R mice. The BBB permeability in diabetic CI/R mice and HG-treated OGD/R cells was increased, while the junction integrity was decreased. Interference with TRIB3 in vitro reduces BBB permeability and increases junction integrity. In vivo interfering with TRIB3 reduced cerebral infarction volume, BBB permeability and inflammation levels, and upregulated p-AKT levels. The phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin reversed the effects of TRIB3-interfering plasmid. In vitro HG treatment induced TRIB3 acetylation through acetyltransferase p300, which in turn reduced ubiquitination and stabilized TRIB3. Interfering TRIB3 protects BBB by activating PI3K/AKT pathway and alleviates brain injury, which provides a new target for diabetic CI/RI.
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Isquemia Encefálica , Diabetes Mellitus , Daño por Reperfusión , Ratones , Animales , Barrera Hematoencefálica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células Endoteliales , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasa/farmacología , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Infarto Cerebral/metabolismo , Oxígeno/metabolismo , Glucosa/metabolismo , Acetiltransferasas/metabolismo , Acetiltransferasas/farmacología , Diabetes Mellitus/metabolismoRESUMEN
As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing.
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Caenorhabditis elegans , Factores de Diferenciación de Crecimiento , Adulto , Ratones , Humanos , Animales , Caenorhabditis elegans/metabolismo , Factores de Diferenciación de Crecimiento/genética , Factores de Diferenciación de Crecimiento/metabolismo , Envejecimiento/genética , Encéfalo/metabolismo , Neuronas/metabolismo , Proteínas Morfogenéticas ÓseasRESUMEN
Accurate stroke assessment and consequent favorable clinical outcomes rely on the early identification and quantification of aneurysmal subarachnoid hemorrhage (aSAH) in non-contrast computed tomography (NCCT) images. However, hemorrhagic lesions can be complex and difficult to distinguish manually. To solve these problems, here we propose a novel Hybrid 2D/3D UNet deep-learning framework for automatic aSAH identification and quantification in NCCT images. We evaluated 1824 consecutive patients admitted with aSAH to four hospitals in China between June 2018 and May 2022. Accuracy and precision, Dice scores and intersection over union (IoU), and interclass correlation coefficients (ICC) were calculated to assess model performance, segmentation performance, and correlations between automatic and manual segmentation, respectively. A total of 1355 patients with aSAH were enrolled: 931, 101, 179, and 144 in four datasets, of whom 326 were scanned with Siemens, 640 with Philips, and 389 with GE Medical Systems scanners. Our proposed deep-learning method accurately identified (accuracies 0.993-0.999) and segmented (Dice scores 0.550-0.897) hemorrhage in both the internal and external datasets, even combinations of hemorrhage subtypes. We further developed a convenient AI-assisted platform based on our algorithm to assist clinical workflows, whose performance was comparable to manual measurements by experienced neurosurgeons (ICCs 0.815-0.957) but with greater efficiency and reduced cost. While this tool has not yet been prospectively tested in clinical practice, our innovative hybrid network algorithm and platform can accurately identify and quantify aSAH, paving the way for fast and cheap NCCT interpretation and a reliable AI-based approach to expedite clinical decision-making for aSAH patients.
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Aprendizaje Profundo , Accidente Cerebrovascular , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Medios de ContrasteRESUMEN
PURPOSE: Glioblastoma (GBM) is a highly vascularized tumor with few treatment options after disease recurrence. Here, we report the efficacy and safety of anlotinib hydrochloride plus temozolomide in patients with recurrent GBM. PATIENTS AND METHODS: Patients with first definite postsurgical progression of histologically confirmed GBM preceded by standard radiotherapy and temozolomide chemotherapy were eligible for inclusion. All patients received temozolomide (150-200 mg/m2, orally, every day (QD) d1-5/4 wk) and anlotinib (10 mg, orally, QD, d1-14/3 wk) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by the Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: Twenty-one patients were enrolled between May 2020 and July 2021, with a median age of 55 (range 27-68) years old. According to the Response Assessment in Neuro-Oncology (RANO) criteria, tumor response occurred in 17 patients, of which 9 patients had a complete response, and the objective response rate was 81.0% [95% confidence interval (CI), 62.6-99.3]. The disease control rate was 95.2% (95% CI, 76.2-99.9), with three additional patients achieving a stable disease without tumor progression. The median PFS was 7.3 months (95% CI, 4.9-9.7), and the 6-month PFS rate was 61.9% (95% CI, 39.3-84.6). The median overall survival was 16.9 months (95% CI, 7.8-26.0). The most common adverse events were leukocytopenia (66.7%), thrombocytopenia (38.1%), and hypertriglyceridemia (38.1%). Five patients had nine grade 3 adverse events, with a 23.8% incidence rate. Two patients discontinued therapy due to ischemic stroke (grade 3) and wound dehiscence (grade 1), respectively. No grade 4 or treatment-related deaths occurred in this study. CONCLUSIONS: Anlotinib combined with temozolomide is efficacious and tolerated in patients with recurrent GBM.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Adulto , Persona de Mediana Edad , Anciano , Temozolomida/efectos adversos , Glioblastoma/patología , Dacarbazina , Neoplasias Encefálicas/patología , Recurrencia Local de Neoplasia/patología , Inhibidores de la Angiogénesis/uso terapéuticoRESUMEN
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).
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Background: Spinal schwannomas (SSs) are benign tumors affecting the nerve sheath, accounting for 25% of spinal nerve root tumors. Surgery represents the mainstay of treatment for SS patients. Following surgery, approximately 30% of patients experienced developed new or worsening neurological deterioration, which probably represented an inevitable complication of nerve sheath tumor surgery. The objective of this study was to identify the rates of new or worsening neurological deterioration in our center and accurately predict the neurological outcomes of patients with SS by developing a new scoring model. Methods: A total of 203 patients were retrospectively enrolled at our center. Risk factors associated with postoperative neurological deterioration were identified by multivariate logistic regression analysis. ß-coefficients for independent risk factors were used to define a numerical score to generate a scoring model. The validation cohort at our center was used to verify the accuracy and reliability of the scoring model. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the scoring model. Results: In this study, five measured variables were selected for the scoring model: duration of preoperative symptoms (1 point), radiating pain (2 points), tumor size (2 points), tumor site (1 point), and dumbbell tumor (1 point). The scoring model divided the spinal schwannoma patients into three categories: low risk (0-2 points), intermediate risk (3-5 points), and high risk (6-7 points), with predicted risks of neurological deterioration of 8.7%, 36%, and 87.5%, respectively. And the validation cohort confirmed the model with the predicted risks of 8.6%, 46.4%, and 66.6%, respectively. Conclusion: The new scoring model might intuitively and individually predict the risk of neurological deterioration and may aid individualized treatment decision-making for SS patients.
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Background and purpose: The unruptured intracranial aneurysm (UIA) has high disability and mortality rate after rupture, it is particularly important to assess the risk of UIA and to carry out individualized treatment. The objective of this research is to introduce a novel parameter to predict the rupture risk of UIA. Methods: A total of 649 patients with 964 intracranial aneurysms in our center were enrolled. A novel parameter named mean arterial pressure-aneurysmal neck ratio (MAPN) was defined. Ten baseline clinical features and twelve aneurysm morphological characteristics were extracted to generate the MAPN model. The discriminatory performance of the MAPN model was compared with the PHASES score and the UCAS score. Results: In hemodynamic analysis, MAPN was positively correlated with wall shear stress and aneurysm top pressure, with Pearson correlation coefficients of 0.887 and 0.791, respectively. The MAPN was larger in the ruptured group (36.62 ± 18.96 vs. 28.38 ± 14.58, P < 0.001). The area under the curve (AUC) of the MAPN was superior than the AUC of aspect ratio (AR) and the bottleneck factor (BN), they were 0.64 (P < 0.001; 95% CI, 0.588-0.692), 0.611 (P < 0.001; 95% CI, 0.559-0.663) and 0.607 (P < 0.001; 95% CI, 0.554-0.660), respectively. The MAPN model constructed by aneurysm size, aneurysm location, presence of secondary sacs and MAPN, demonstrated good discriminatory ability. The MAPN model exhibited superior performance compared with the UCAS score and the PHASES score (the AUC values were 0.799 [P < 0.001; 95% CI, 0.756-0.840], 0.763 [P < 0.001; 95% CI,0.719-0.807] and 0.741 [P < 0.001; 95% CI, 0.695-0.787], respectively; the sensitivities were 0.849, 0.758 and 0.753, respectively). Conclusions: Research demonstrates the potential of MAPN to augment the clinical decision-making process for assessing the rupture risk of UIAs.
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The tumor microenvironment (TME), comprising cancer cells and stroma, plays a significant role in determining clinical outcomes, which makes targeting cancer cells in the TME an important area of research. One way in which cancer cells in the TME can be specifically targeted is by coating drug-encapsulated nanoparticles (NPs) with homotypic cancer cell membranes. However, incomplete targeting is inevitable for biomimetic nanoformulations coated with only cancer cell membranes because of the inherent heterogeneity of the TME. After observing the structural connection between glioma-associated stromal cells (GASCs) and glioma cells from a clinic, we designed a novel drug delivery system that targets the TME by coating polylactic-co-glycolic acid (PLGA) NPs with GASC-glioma cell fusion cell (SG cell) membranes. The resulting SGNPs inherited membrane proteins from both the glioma membrane and GASC membrane, significantly enhancing the tumor targeting efficiency compared to nanoformulations coated with cancer cell membranes alone. We further demonstrated that encapsulation of temozolomide (TMZ) improved the therapeutic efficacy of TMZ in both heterotopic and orthotopic glioma mouse models. Owing to its significant efficacy, our TME-targeting nanoplatform has potential for clinical applications in the treatment of various cancers.
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Glioma , Nanopartículas , Ratones , Animales , Microambiente Tumoral , Glioma/patología , Sistemas de Liberación de Medicamentos/métodos , Temozolomida/uso terapéutico , Membrana Celular/metabolismo , Nanotecnología , Nanopartículas/química , Línea Celular TumoralRESUMEN
Early brain injury is a series of pathophysiological changes and direct damage of brain tissue within 72 h after subarachnoid hemorrhage before cerebral vasospasm occurs. Early brain injury is a key factor affecting the prognosis of subarachnoid hemorrhage, and its possible pathological mechanisms include oxidative stress, cell apoptosis, autophagy, and immune inflammation. Microglia are important immune cells of the central nervous system. Microglia play a dual role in protection and injury. Microglia are involved in the occurrence of brain edema, the processes of neuronal apoptosis, and the blood-brain barrier disruption after subarachnoid hemorrhage (SAH) through the signaling pathways mediated by receptors such as Toll-like receptor 4 (TLR4), calcium-sensing receptor (CaSR), and triggering receptor expressed on myeloid cells-1 (TREM-1), which secrete pro-inflammatory cytokines such as interleukins and tumor necrosis factor α. Conversely, they exert their anti-inflammatory and protective effects by expressing substances such as neuroglobin and heme oxygenase-1. This article reviews the latest developments in single-cell transcriptomics for microglia in early brain injury after subarachnoid hemorrhage and its inflammatory role.
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(1) Background: CC chemokine ligand 23 (CCL23) is a chemokine implicated in the inflammatory response following brain damage. The aim of this study is to identify the change in serum CCL23 levels within 24 h after aSAH and whether serum CCL23 levels are associated with initial clinical severity, delayed cerebral ischemia (DCI), and functional outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). (2) Methods: 102 patients with aSAH and 61 controls were included in this prospective observational study. All clinical data were collected prospectively, and their serum CCL23 levels were measured. Initial clinical severity was reflected by the Hunt-Hess score and mFisher score. Functional outcome was evaluated in terms of the Glasgow Outcome Scale (GOS) score at 6-month follow-up. (3) Results: Patients with aSAH had higher serum CCL23 levels than controls. The temporal profile of serum CCL23 levels and neutrophils count exhibited a sustained increase within 24 h after aSAH. Serum CCL23 levels were related to blood neutrophils count, blood CRP levels, and initial clinical severity. Serum CCL23 level was an independent predictor of DCI and 6-month poor outcome in aSAH patients. (4) Conclusions: Serum CCL23 levels emerged as an independent predictor for DCI and poor outcome in patients with aSAH.
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BACKGROUND: CCL23 is involved in the inflammatory response and associated with the progression of brain injury. Herein, we assessed the relationship between serum CCL23 levels and inflammation, hematoma severity, and unfavorable outcome after intracerebral hemorrhage (ICH). METHODS: In this prospective observational study of 94 ICH patients and 47 controls, serum CCL23 levels were measured. Hemorrhage severity was reflected by the National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume. An unfavorable outcome was defined as a modified Rankin Scale > 2 at 6 months after ICH. Its association with clinical outcome was confirmed using the binary logistic regression analysis. Predictive efficiency was verified under receiver operating characteristic (ROC) curve. RESULTS: Significantly increased serum CCL23 levels were observed in ICH patients, as compared to controls. Serum CCL23 levels were highly related to NIHSS score, hematoma volume, ICH score, Glasgow coma scale score, serum C-reactive protein levels, blood leucocyte count, and neutrophil count. CCL23 ≥ 62.95 pg/ml served as an independent predictor of 6-month unfavorable outcome and death, and its validity was confirmed by ROC analysis. CONCLUSION: CCL23 may be implicated in the inflammatory response and serve as a potential marker for predicting the prognosis of patients with ICH.
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Hemorragia Cerebral , Hematoma , Humanos , Hemorragia Cerebral/diagnóstico , Biomarcadores , Curva ROC , Pronóstico , Quimiocinas CCRESUMEN
Ischemic stroke is a leading cause of disability and death. It imposes a heavy economic burden on individuals, families and society. The mortality rate of ischemic stroke has decreased with the help of thrombolytic drug therapy and intravascular intervention. However, the nerve damage caused by ischemia-reperfusion is long-lasting and followed by multiple organ dysfunction. In this process, the immune responses manifested by systemic inflammatory responses play an important role. It begins with neuroinflammation following ischemic stroke. The large number of inflammatory cells released after activation of immune cells in the lesion area, along with the deactivated neuroendocrine and autonomic nervous systems, link the center with the periphery. With the activation of systemic immunity and the emergence of immunosuppression, peripheral organs become the second "battlefield" of the immune response after ischemic stroke and gradually become dysfunctional and lead to an adverse prognosis. The purpose of this review was to describe the systemic immune responses after ischemic stroke. We hope to provide new ideas for future research and clinical treatments to improve patient outcomes and quality of life.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Fibrinolíticos , Humanos , Inmunidad , Calidad de VidaRESUMEN
The immune microenvironment of glioma attributes to the initiation and development of glioma; however, the underlying mechanisms of tumor microenvironment formation have not been fully understood. In this study, we revealed that Zinc Finger Protein 395 (ZNF395), a member of the Kruppel C2H2-type zinc-finger protein family and also known as a common transcription factor, was aberrantly overexpressed in glioma and positively associated with the poor clinicopathological features and the prognosis of patients with glioma based on the analyses of TCGA, CGGA and other datasets. Further in vitro experimental data demonstrated that the upregulation of ZNF395 promoted the proliferation of glioma cells. In addition, functional enrichment analysis showed that ZNF395 was involved in immune processes and correlated with macrophage infiltration and polarization. Moreover, C-C Motif Chemokine Ligand 20 (CCL20), one of the ZNF395 co-expressed genes, was validated as the downstream factor under the transcriptional regulation of ZNF395. Importantly, cell co-culture experiments confirmed that ZNF395 upregulated both the intracellular and secreted CCL20 level of glioma cells and induced M2 macrophage polarization which is known to promote the malignant progression of glioma. Taken together, our findings suggested that ZNF395 might play an essential role in glioma development, and inhibition of ZNF395 might be a plausible strategy for glioma therapy.
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BACKGROUND: Ophthalmic segment artery aneurysms (OSAs) are difficult to clip; therefore, improvement of the surgical method is of great significance to the prevention of complications, and the classification of the aneurysms is essential to formulate a reasonable surgical plan. OBJECTIVE: To explore the strategies and effects of surgery for OSAs using a modified subdural Dolenc approach. METHODS: The clinical data of 38 patients (12 men and 26 women, aged 48-73 years) with OSA were analyzed retrospectively. A total of 44 aneurysms were identified, 40 of which were OSAs. The 40 aneurysms were divided into types Ia1 (n = 2), Ia2 (n = 2), Ib (n = 6), IIa (n = 4), IIb (n = 4), IIIa (n = 0), IIIb (n = 4), IIIc (n = 16), and IV (n = 2) based on preoperative images. Thirty-nine OSAs were operated successfully through pterional craniotomy combined with the modified subdural Dolenc approach, and 1 aneurysm was clipped through the contralateral approach. Clinical outcomes were evaluated using the Glasgow Outcome Scale (GOS). RESULTS: Thirty-nine OSAs were clipped, and one was wrapped. Visual dysfunction, headache, and dizziness improved after the operation in 18 patients. One patient had new visual impairment, and there were no deaths. At discharge, the GOS score was 5 in 36 cases, 4 in 1 case, and 3 in 1 case. Thirty-seven patients had a GOS score of 5, and 1 patient had a score of 3 at 6 months after the operation. CONCLUSION: The modified subdural Dolenc approach (Zheng approach) for clipping OSAs may be associated with less trauma and good postoperative outcomes.
Asunto(s)
Aneurisma Intracraneal , Femenino , Humanos , Masculino , Craneotomía/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Arteria Oftálmica , Estudios RetrospectivosRESUMEN
Glioblastoma is one of the central nervous system most aggressive and lethal cancers with poor overall survival rate. Systemic treatment of glioblastoma remains the most challenging aspect due to the low permeability of the blood-brain barrier (BBB) and blood-tumor barrier (BTB), limiting therapeutics extravasation mainly in the core tumor as well as in its surrounding invading areas. It is now possible to overcome these barriers by using low-intensity focused ultrasound (LIFU) together with intravenously administered oscillating microbubbles (MBs). LIFU is a non-invasive technique using converging ultrasound waves which can alter the permeability of BBB/BTB to drug delivery in a specific brain/tumor region. This emerging technique has proven to be both safe and repeatable without causing injury to the brain parenchyma including neurons and other structures. Furthermore, LIFU is also approved by the FDA to treat essential tremors and Parkinson's disease. It is currently under clinical trial in patients suffering from glioblastoma as a drug delivery strategy and liquid biopsy for glioblastoma biomarkers. The use of LIFU+MBs is a step-up in the world of drug delivery, where onco-therapeutics of different molecular sizes and weights can be delivered directly into the brain/tumor parenchyma. Initially, several potent drugs targeting glioblastoma were limited to cross the BBB/BTB; however, using LIFU+MBs, diverse therapeutics showed significantly higher uptake, improved tumor control, and overall survival among different species. Here, we highlight the therapeutic approach of LIFU+MBs mediated drug-delivery in the treatment of glioblastoma.