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To study a case of a middle-aged male with a non-tumor-associated Epstein-Barr virus (EBV) infection associated with Anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), to explore the role of EBV in the pathogenesis of anti-NMDARE. The patient was diagnosed with "Anti-NMDARE, EBV infection" by using Cerebrospinal fluid (CSF) autoimmune encephalitis profile, and Metagenomics Next-Generation Sequencing (mNGS) pathogenic microbial assays, we discuss the relationship between EBV and NMDARE by reviewed literature. EBV infection may trigger and enhance anti-NMDARE, and the higher the titer of NMDAR antibody, the more severe the clinical presentation.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Infecções por Vírus Epstein-Barr , Doença de Hashimoto , Pessoa de Meia-Idade , Humanos , Masculino , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4 , Doença de Hashimoto/complicaçõesRESUMO
Background: Cuproptosis is a newly discovered unique non-apoptotic programmed cell death distinguished from known death mechanisms like ferroptosis, pyroptosis, and necroptosis. However, the prognostic value of cuproptosis and the correlation between cuproptosis and the tumor microenvironment (TME) in lower-grade gliomas (LGGs) remain unknown. Methods: In this study, we systematically investigated the genetic and transcriptional variation, prognostic value, and expression patterns of cuproptosis-related genes (CRGs). The CRG score was applied to quantify the cuproptosis subtypes. We then evaluated their values in the TME, prognostic prediction, and therapeutic responses in LGG. Lastly, we collected five paired LGG and matched normal adjacent tissue samples from Sun Yat-sen University Cancer Center (SYSUCC) to verify the expression of signature genes by quantitative real-time PCR (qRT-PCR) and Western blotting (WB). Results: Two distinct cuproptosis-related clusters were identified using consensus unsupervised clustering analysis. The correlation between multilayer CRG alterations with clinical characteristics, prognosis, and TME cell infiltration were observed. Then, a well-performed cuproptosis-related risk model (CRG score) was developed to predict LGG patients' prognosis, which was evaluated and validated in two external cohorts. We classified patients into high- and low-risk groups according to the CRG score and found that patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P<0.001). A high CRG score implies higher TME scores, more significant TME cell infiltration, and increased mutation burden. Meanwhile, the CRG score was significantly correlated with the cancer stem cell index, chemoradiotherapy sensitivity-related genes and immune checkpoint genes, and chemotherapeutic sensitivity, indicating the association with CRGs and treatment responses. Univariate and multivariate Cox regression analyses revealed that the CRG score was an independent prognostic predictor for LGG patients. Subsequently, a highly accurate predictive model was established for facilitating the clinical application of the CRG score, showing good predictive ability and calibration. Additionally, crucial CRGs were further validated by qRT-PCR and WB. Conclusion: Collectively, we demonstrated a comprehensive overview of CRG profiles in LGG and established a novel risk model for LGG patients' therapy status and prognosis. Our findings highlight the potential clinical implications of CRGs, suggesting that cuproptosis may be the potential therapeutic target for patients with LGG.
Assuntos
Apoptose , Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Glioma/genética , Glioma/terapia , Mutação , Gradação de Tumores , Prognóstico , Microambiente Tumoral/genética , CobreRESUMO
Clear cell renal cell carcinoma (ccRCC) is the most common histological and devastating subtype of renal cell carcinoma. Necroptosis is a form of programmed cell death that causes prominent inflammatory responses. miRNAs play a significant role in cancer progression through necroptosis. However, the prognostic value of necroptosis-related miRNAs remains ambiguous. In this study, 39 necroptosis-related miRNAs (NRMs) were extracted and 17 differentially expressed NRMs between normal and tumor samples were identified using data form The Cancer Genome Atlas (TCGA). After applying univariate Cox proportional hazard regression analysis and LASSO Cox regression model, six necroptosis-related miRNA signatures were identified in the training cohort and their expression levels were verified by qRT-PCR. Using the expression levels of these miRNAs, all patients were divided into the high- and low-risk groups. Patients in the high-risk group showed poor overall survival (P < 0.0001). Time-dependent ROC curves confirmed the good performance of our signature. The results were verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression models demonstrated that the risk score was an independent prognostic factor. Additionally, a predictive nomogram with good performance was constructed to enhance the implementation of the constructed signature in a clinical setting. We then employed miRBD, miRTarBase, and TargetScan to predict the target genes of six necroptosis-related miRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that 392 potential target genes were enriched in cell proliferation-related biological processes. Six miRNAs and 59 differentially expressed target genes were used to construct an miRNA-mRNA interaction network, and 11 hub genes were selected for survival and tumor infiltration analysis. Drug sensitivity analysis revealed potential drugs that may contribute to cancer management. Hence, necroptosis-related genes play an important role in cancer biology. We developed, for the first time, a necroptosis-related miRNA signature to predict ccRCC prognosis.
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Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Necroptose/genéticaRESUMO
Renshen Yangrong Decoction has been used to treat asthenic disease symptoms, such as exhaustion, and qi and blood deficiency diseases. It not only promotes hematopoietic function and improve immune functions, but also alleviates coronary heart diseases, diabetic complications, malignant tumor, and brain injury. It has satisfactory curative effect on sleep disorders and fatigue. Herein, we provide an overview of fundamental research on Renshen Yangrong Decoction focusing on its hematopoietic and immune functions and the status of clinical research with regard to the above-mentioned diseases in recent years.
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Hydrogen (H(2)) acts as a therapeutic antioxidant. However, there are few reports on H(2) function in other capacities in diabetes mellitus (DM). Therefore, in this study, we investigated the role of H(2) in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ)-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H(2) promoted 2-[(14)C]-deoxy-d-glucose (2-DG) uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K), protein kinase C (PKC), and AMP-activated protein kinase (AMPK), although it did not stimulate the translocation of Glut2 in Hep G2 cells. H(2) significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p.) and oral (p.o.) administration. However, long-term p.o. administration of H(2) had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H(2) exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.
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Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hidrogênio/administração & dosagem , Músculo Esquelético/efeitos dos fármacos , Quinases Proteína-Quinases Ativadas por AMP , Animais , Glicemia/efeitos dos fármacos , Cricetinae , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Células Hep G2 , Humanos , Camundongos , Músculo Esquelético/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Quinase C/metabolismo , Proteínas Quinases/metabolismoRESUMO
The objective of this study was to clarify the role of a novel agonist with high selectivity and affinity for Y4 receptors in the regulation of food intake. The Y4 receptor agonist BVD-74D was administered to C57BL/6J mice that were fed with a normal or high-fat diet, and to fatty liver Shionogi (FLS)-ob/ob mice; the food intake, water intake, and body weight gain were measured in these mice. In the mice fed with a normal diet, the cumulative food intake significantly decreased at 20 min and 1 h after the administration of 1 mg/kg of BVD-74D and at 1, 2, 4, 8, and 24 h after the administration of 10 mg/kg of BVD-74D. Moreover, the cumulative water intake and body weight gain significantly decreased in these mice. Among the mice that were fed with a high-fat diet, the cumulative food intake and water intake significantly decreased 1, 2, and 4 h after BVD-74D (10 mg/kg) administration. Furthermore, the cumulative food intake significantly decreased 2 and 4 h after BVD-74D (10 mg/kg) administration in the FLS-ob/ob mice. Thus, we propose that the novel Y4 receptor agonist BVD-74D has suppressive effects on food intake, water intake, and weight gain in normal mice fed with normal diets and on food intake in normal mice fed with high-fat diets and in FLS-ob/ob mice. These findings indicate that the Y4 receptor and its agonist would be promising targets for obesity.